Natural selection in Britain during the last 2,000 years

The latest ancient DNA studies from the British Isles (Schiffels et al and Martiniano et al. and Cassidy et al.) support continuity over the last 2,000 years. Sure, there were continued migrations like the arrival of the Anglo-Saxons, but these were very similar groups in the grand scheme of things.

But, while ancestrally the modern Briton is probably a descendant of the Britons of 2,000 years ago with some admixture from similar continental European groups, he is not the same, as (apparently) substantial genetic adaptation has continued to operate in Britain over the same period. A new preprint by Field, Boyle, Telis et al. makes the case for adaptation in a variety of traits in the ancestors of Britons over this period. Mind you, the genetic underpinnings of many important human traits known to have high heritability are currently unknown, but there is little doubt that selection would have affected traits beyond those detected in this study. I am quite curious to see whether the striking efflorescence of cultural achievement in Britain over the last half millennium could have (at least in part) a genetic underpinning.

Depigmentation is a trait whose genetic architecture is as well as understood as any. The results of this study might surprise writers of decades and centuries past who supposed that the spectrum of pigmentation of modern Europeans was the result  of admixture-in varying measure- between Xanthochrooi and Melanchrooi races of primordial antiquity. All indications seem to be that depigmentation of hair, skin, and eyes did not co-occur in such a hypothetical race, but rather in different parts of the Caucasoid range, only reaching a high combined frequency in northern Europe to form the distinctive physical type that is distinctive of the natives of that region. It would be quite interesting to see how these traits evolved in Fennoscandia and the Baltic, regions that sport an even higher depigmentation than the British Isles. Traditionally, these areas were viewed as refuges of the Xanthochrooi but it may very well turn out to be that for whatever reason selection has acted in that area as well, as it did in the Eastern European plain where rather dark Bronze Age steppe groups gave way to rather light pigmented living eastern Slavs.

bioRxiv doi: http://dx.doi.org/10.1101/052084

Detection of human adaptation during the past 2,000 years

Yair Field, Evan A Boyle, Natalie Telis, Ziyue Gao, Kyle J Gaulton, David Golan, Loic Yengo, Ghislain Rocheleau, Philippe Froguel, Mark I McCarthy, Jonathan K Pritchard

Detection of recent natural selection is a challenging problem in population genetics, as standard methods generally integrate over long timescales. Here we introduce the Singleton Density Score (SDS), a powerful measure to infer very recent changes in allele frequencies from contemporary genome sequences. When applied to data from the UK10K Project, SDS reflects allele frequency changes in the ancestors of modern Britons during the past 2,000 years. We see strong signals of selection at lactase and HLA, and in favor of blond hair and blue eyes. Turning to signals of polygenic adaptation we find, remarkably, that recent selection for increased height has driven allele frequency shifts across most of the genome. Moreover, we report suggestive new evidence for polygenic shifts affecting many other complex traits. Our results suggest that polygenic adaptation has played a pervasive role in shaping genotypic and phenotypic variation in modern humans.

Link

Stature/body mass index and socioeconomic status

BMJ 2016; 352 doi: http://dx.doi.org/10.1136/bmj.i582 (Published 08 March 2016)

Height, body mass index, and socioeconomic status: mendelian randomisation study in UK Biobank 

Jessica Tyrrell, research fellow1 2, Samuel E Jones, associate research fellow1, Robin Beaumont, associate research fellow1, Christina M Astley, research fellow3 4, Rebecca Lovell, research fellow2, Hanieh Yaghootkar, research fellow1, Marcus Tuke, associate research fellow1, Katherine S Ruth, associate research fellow1, Rachel M Freathy, senior research fellow1, Joel N Hirschhorn, professor2 3 5, Andrew R Wood, research fellow1, Anna Murray, senior lecturer1, Michael N Weedon, associate professor1, Timothy M Frayling, professor1

Abstract

Objective To determine whether height and body mass index (BMI) have a causal role in five measures of socioeconomic status.

Design Mendelian randomisation study to test for causal effects of differences in stature and BMI on five measures of socioeconomic status. Mendelian randomisation exploits the fact that genotypes are randomly assigned at conception and thus not confounded by non-genetic factors.

Setting UK Biobank.

Participants 119 669 men and women of British ancestry, aged between 37 and 73 years.

Main outcome measures Age completed full time education, degree level education, job class, annual household income, and Townsend deprivation index.

Results In the UK Biobank study, shorter stature and higher BMI were observationally associated with several measures of lower socioeconomic status. The associations between shorter stature and lower socioeconomic status tended to be stronger in men, and the associations between higher BMI and lower socioeconomic status tended to be stronger in women. For example, a 1 standard deviation (SD) higher BMI was associated with a £210 (€276; $300; 95% confidence interval £84 to £420; P=6×10−3) lower annual household income in men and a £1890 (£1680 to £2100; P=6×10−15) lower annual household income in women. Genetic analysis provided evidence that these associations were partly causal. A genetically determined 1 SD (6.3 cm) taller stature caused a 0.06 (0.02 to 0.09) year older age of completing full time education (P=0.01), a 1.12 (1.07 to 1.18) times higher odds of working in a skilled profession (P=6×10−7), and a £1130 (£680 to £1580) higher annual household income (P=4×10−8). Associations were stronger in men. A genetically determined 1 SD higher BMI (4.6 kg/m2) caused a £2940 (£1680 to £4200; P=1×10−5) lower annual household income and a 0.10 (0.04 to 0.16) SD (P=0.001) higher level of deprivation in women only.

Conclusions These data support evidence that height and BMI play an important partial role in determining several aspects of a person’s socioeconomic status, especially women’s BMI for income and deprivation and men’s height for education, income, and job class. These findings have important social and health implications, supporting evidence that overweight people, especially women, are at a disadvantage and that taller people, especially men, are at an advantage.

Link

Why Europeans gained 11cm in height in a century

The paper's conclusion:

The main findings in this article can be summarized as follows. New data show that average male height in Europe increased by about 11 cm in the century from the 1870s—representing an unprecedented improvement in health status. In northern and middle European countries there was a distinct quickening in the pace of advance in the period spanning the two world wars and the Great Depression, which largely predates the modern medicine and national health services. In southern Europe height increased fastest in the postwar period. There is evidence of a concave health production function, but the effects of inequality are not robust. Education had a positive effect on height and family size a negative effect, consistent with the quality-quantity trade-off. The evidence suggests that improvements in the disease environment, as reflected in infant mortality, is the single most important factor driving the increase in height. This accounts for much of the acceleration during the transwar period. Social services and health systems made a modest contribution to the overall increase in height. One reason is that education and expenditure on social services seem to be substitutes. Transport infrastructure also contributed to health and height, especially in the prewar era. But a substantial part of the overall upwards trend in height is not explained—in the absence of infant mortality, about a half. There are other important factors that are not easily measured, including medical advances and practices, and especially better parental knowledge of the effects of nutrition and hygiene on children’s health.

Oxf. Econ. Pap. (2013)
doi: 10.1093/oep/gpt030

How have Europeans grown so tall?

Timothy J. Hatton

Increases in human stature are a key indicator of improvements in the average health of populations. In this article I present and analyse a new data set for the average height of adult male birth cohorts, from the mid-nineteenth century to 1980, in 15 European countries. In little more than a century average height increased by 11 cm—representing a dramatic improvement in health. Interestingly, there was some acceleration in the period spanning the two world wars and the Great Depression. The evidence suggests that the most important proximate source of increasing height was the improving disease environment as reflected by the fall in infant mortality. Rising income and education and falling family size had more modest effects. Improvements in health care are hard to identify, and the effects of welfare state spending seem to have been small.

Link

Assortative mating for height in the UK

PLoS ONE 8(1): e54186. doi:10.1371/journal.pone.0054186

Are Human Mating Preferences with Respect to Height Reflected in Actual Pairings?

Gert Stulp et al.

Pair formation, acquiring a mate to form a reproductive unit, is a complex process. Mating preferences are a step in this process. However, due to constraining factors such as availability of mates, rival competition, and mutual mate choice, preferred characteristics may not be realised in the actual partner. People value height in their partner and we investigated to what extent preferences for height are realised in actual couples. We used data from the Millennium Cohort Study (UK) and compared the distribution of height difference in actual couples to simulations of random mating to test how established mate preferences map on to actual mating patterns. In line with mate preferences, we found evidence for: (i) assortative mating (r = .18), (ii) the male-taller norm, and, for the first time, (iii) for the male-not-too-tall norm. Couples where the male partner was shorter, or over 25 cm taller than the female partner, occurred at lower frequency in actual couples than expected by chance, but the magnitude of these effects was modest. We also investigated another preference rule, namely that short women (and tall men) prefer large height differences with their partner, whereas tall women (and short men) prefer small height differences. These patterns were also observed in our population, although the strengths of these associations were weaker than previously reported strength of preferences. We conclude that while preferences for partner height generally translate into actual pairing, they do so only modestly.

Link

New evidence for archaic admixture in African hunter gatherers (Lachance et al. 2012)

At the end of last year I predicted that full genome sequencing would begin turning up evidence for more archaic admixture in Africa. Halfway into the year, it appears that my prediction has proven to be correct: a new study in Cell by Lachance et al. documents the existence of such admixture between an archaic hominin and Pygmies from Cameroon, and the East African Hadza and Sandawe.

Archaic admixture in Biaka and San was previously detected by Hammer et al. Hence, we now have evidence for archaic admixture from several regions that encompass all major regions within sub-Saharan Africa. It seems that my old idea about layers of Palaeoafricans being absorbed by early modern humans in Africa was basically correct, and that some of these layers correspond to archaic African populations.

But not all agree. The New York Times coverage of the paper suggests that there is a controversy surrounding the new study:

All human fossil remains in Africa for the last 100,000 years, and probably the last 200,000 years, are of modern humans, providing no support for a coexistent archaic species. 

... 

Paleoanthropologists like Dr. Klein consider it “irresponsible” of the geneticists to publish genetic findings about human origins without even trying to show how they may fit in with the existing fossil and archaeological evidence. Dr. Akey said he agreed that genetics can provide only part of the story. “But hopefully this is just a period when new discoveries are being made and there hasn’t been enough incubation time to synthesize all the disparities,” he said.

This is of course completely wrong; as Chris Stringer mentions in the NY Times piece, there is ample evidence for archaic Africans down to quite recent times in the form of Iwo Eleru and Ishango, and there is more evidence besides. Indeed, it does not appear at all that there was a punctuational event that replaced archaic hominins with a new Homo sapiens species. If anyone wants to criticize the new study, complaining about it being in disharmony with physical anthropology is not a good way to go about it. Nor is it, of course, "irresponsible" to report the new findings.  And, apparently, there is more on the way:

In a report still under review, a third group of geneticists says there are signs of Neanderthals having interbred with Asians and East Africans. But Neanderthals were a cold-adapted species that never reached East Africa.

Things are bound to become quite interesting.

From the paper:

A striking finding in our data set is that compelling evidence exists that extant hunter-gatherer genomes contain introgressed archaic sequence, consistent with previous studies (Hammer et al., 2011; Plagnol and Wall, 2006; Reich et al., 2010; Shimada et al., 2007; Wall et al., 2009). We note that unambiguous evidence of introgression is difficult to obtain in the absence of an archaic reference sequence, which currently does not exist and may never be feasible given the rapid decay of fossils in Africa. Although we carefully filtered our data set in an attempt to analyze only high-quality sequences (Supplementary Information), it is possible that unrecognized structural variants or other alignment errors could generate a spurious signature similar to introgression. Encouragingly, we did not see an enrichment of structural variation calls in our candidate introgression regions. Additionally, through extensive simulations and analysis of European whole-genome sequences (Supplementary Information), we have demonstrated that the signatures of introgression that we observed are unlikely to be entirely accounted for due to other aspects of population demographic history, natural selection, or sequencing errors. Moreover, we did not find strong evidence that introgressed regions were clustered in the genome more often than expected by chance (p > 0.05; Supplemental Information). Nor did we find significant evidence that introgressed regions were enriched in genic regions (p > 0.05); rather, genic regions were significantly depleted for introgression in several populations (Supplemental Information). Therefore, the simplest interpretation of these data is that introgressed regions in extant human populations represent neutrally evolving vestiges of archaic sequences. In short, we find that low levels of introgression from an unknown archaic population or populations occurred in the three African hunter-gatherer samples examined, consistent with findings of archaic admixture in non-Africans (Reich et al., 2010). 

What are the implications of the new research? Where did modern humans actually originate and how can their archaic admixture be explained?

One possible explanation, consistent with multi-regional evolution (MRE) theory, is that modern humans didn't originate anywhere in particular; they emerged out of Homo populations that lived everywhere. And, certainly, the discovery of archaic admixture of a local origin is quickly reducing the number of places where the common ancestors of modern humans could have begun their expansion. Western Eurasia is out due to Neandertals; East Eurasia and Oceania is out due to Denisovans; the entirety of Sub-Saharan Africa seems to also be out. North Africa and Southwest Asia appear to be the only remaining candidates.

I don't particularly agree with MRE; one of its predictions (about the relevance of archaic hominins to the human story) has proven to be correct: it increasingly seems that there never was a new Homo sapiens species that was in reproductive isolation from the rest of the Homo genus. On the other hand, the existence of local admixture with different sets of archaic hominins, together with the relative homogeneity of our species is indicative of a range expansion that largely replaced archaic humans -- but not completely.

There does seem to have been a Big Bang of modern humans which caused the demographical explosion of a particular subset of genetic variation. This Big Bang is often associated with Out-of-Africa, but there are good reasons to doubt the traditional 60,000-year old Out-of-Africa theory, according to which humans from South or East Africa crossed into Arabia and followed the coast to populate the world. We now have more reasons to doubt this: evidence of archaic admixture in both the postulated homelands: South Africa, often cited as the region where the first signs of behavioral modernity appear, and East Africa, where the earliest anatomically modern human fossils appear.

My money continues to be on the "two deserts" theory I have proposed some time ago:

• A green Sahara pumping the ancestors of modern humans pre-100 thousand years ago, and 
• a deteriorating green Arabia pumping them post-70 thousand years ago, with some back-migration into Africa.

This would relate the two regions where no evidence (yet?) for archaic humans exist (North Africa and South West Asia), explain the causes of their dispersal (climate change), and harmonize with the evidence for archaic admixture, since the expanding wave of modern humans would partially absorb pre-existing hominins in both Sub-Saharan Africa and across Eurasia.


It must be noted that scientists have been rather conservative in their estimates of archaic admixture in the absence of ancient DNA sequence. Recombination obliterates traces of really old admixture, because introgressed segments become ever smaller, resulting in a pastiche of modern and archaic sequence that no longer looks statistically archaic. But, hopefully, the ever-solidifying case for archaic admixture in our species will finally deal the death blow to tree models, and reveal a much more interesting story of our origins.


Other coverage of the new paper: Nature, Science, ScienceDaily, EurekAlert, Washington Post, SciAm.


Cell doi:10.1016/j.cell.2012.07.009

Evolutionary History and Adaptation from High-Coverage Whole-Genome Sequences of Diverse African Hunter-Gatherers

Joseph Lachance et al.


To reconstruct modern human evolutionary history and identify loci that have shaped hunter-gatherer adaptation, we sequenced the whole genomes of five individuals in each of three different hunter-gatherer populations at >60x coverage: Pygmies from Cameroon and Khoesan-speaking Hadza and Sandawe from Tanzania. We identify 13.4 million variants, substantially increasing the set of known human variation. We found evidence of archaic introgression in all three populations, and the distribution of time to most recent common ancestors from these regions is similar to that observed for introgressed regions in Europeans. Additionally, we identify numerous loci that harbor signatures of local adaptation, including genes involved in immunity, metabolism, olfactory and taste perception, reproduction, and wound healing. Within the Pygmy population, we identify multiple highly differentiated loci that play a role in growth and anterior pituitary function and are associated with height.


Link

Facial attractiveness and interracial marriage

The data:

From the paper:

The results of the experiment demonstrated that there are robust differences in the relative perceived attractiveness of different racial groups. Further, these differences are affected by the gender of the person being rated. Among males, Black faces were rated as the most attractive followed by White faces and then Asian faces. For the females, Asian faces were seen as the most attractive followed by White and then Black faces. The same pattern was found regardless of the ethnicity of the person doing the ratings.

Whatever the perceptions of attractiveness, it seems that people still tend to marry within their own races. For example, in the UK 0.24% of white females marry black males, and the corresponding percentage for the US is 0.56%. Since blacks make up roughly 1/10 of the population in the US, then if race was not an issue, we'd expect white females to marry black males about 10% of the time; the empirical figure is about ~20 times lower.

So, what this study shows is that while intra-racial marriage is still the norm, black males have an easier time overcoming the racial barrier compared to black females, and Asian females compared to Asian males.

The paper does not seem to present any facial attractiveness data, although it does present an analysis to discount an alternative hypothesis based on stature differences. According to that hypothesis, Asian females outmarry more easily than Asian males because Asians are shorter, and women tend to marry taller men than themselves.

PLoS ONE 7(2): e31703. doi:10.1371/journal.pone.0031703


A Facial Attractiveness Account of Gender Asymmetries in Interracial Marriage

Michael B. Lewis


Abstract 
Background
In the US and UK, more Black men are married to White women than vice versa and there are more White men married to Asian women than vice versa. Models of interracial marriage, based on the exchange of racial status for other capital, cannot explain these asymmetries. A new explanation is offered based on the relative perceived facial attractiveness of the different race-by-gender groups.

Method and Findings
This explanation was tested using a survey of perceived facial attractiveness. This found that Black males are perceived as more attractive than White or East Asian males whereas among females, it is the East Asians that are perceived as most attractive on average.

Conclusions
Incorporating these attractiveness patterns into the model of marriage decisions produces asymmetries in interracial marriage similar to those in the observed data in terms of direction and relative size. This model does not require differences in status between races nor different strategies based on gender. Predictions are also generated regarding the relative attractiveness of those engaging in interracial marriage.

Link

Stature of prehistoric Europeans

J Hum Evol. 2011 Dec 22. [Epub ahead of print]

Stature estimation from complete long bones in the Middle Pleistocene humans from the Sima de los Huesos, Sierra de Atapuerca (Spain). 

Carretero JM, Rodríguez L, García-González R, Arsuaga JL, Gómez-Olivencia A, Lorenzo C, Bonmatí A, Gracia A, Martínez I, Quam R.

Abstract Systematic excavations at the site of the Sima de los Huesos (SH) in the Sierra de Atapuerca (Burgos, Spain) have allowed us to reconstruct 27 complete long bones of the human species Homo heidelbergensis. The SH sample is used here, together with a sample of 39 complete Homo neanderthalensis long bones and 17 complete early Homo sapiens (Skhul/Qafzeh) long bones, to compare the stature of these three different human species. Stature is estimated for each bone using race- and sex-independent regression formulae, yielding an average stature for each bone within each taxon. The mean length of each long bone from SH is significantly greater (p < 0.05) than the corresponding mean values in the Neandertal sample. The stature has been calculated for male and female specimens separately, averaging both means to calculate a general mean. This general mean stature for the entire sample of long bones is 163.6 cm for the SH hominins, 160.6 cm for Neandertals and 177.4 cm for early modern humans. Despite some overlap in the ranges of variation, all mean values in the SH sample (whether considering isolated bones, the upper or lower limb, males or females or more complete individuals) are larger than those of Neandertals. Given the strong relationship between long bone length and stature, we conclude that SH hominins represent a slightly taller population or species than the Neandertals. However, compared with living European Mediterranean populations, neither the Sima de los Huesos hominins nor the Neandertals should be considered 'short' people. In fact, the average stature within the genus Homo seems to have changed little over the course of the last two million years, since the appearance of Homo ergaster in East Africa. It is only with the emergence of H. sapiens, whose earliest representatives were 'very tall', that a significant increase in stature can be documented. 

Link

Secular trends in some Russian populations

Anthropol Anz. 2011;68(4):367-77.

Secular trends in some Russian populations.

Godina EZ

Abstract
Secular changes of body measurements in children have been the subject of studies in many different countries. In recent years, there has been an increase in BMI associated with a significant trend towards obesity in both Europe and the US. The aim of the present study was to analyze trends in body measurements and BMI in Russia from the 1960's to the beginning of the 21st century. This was done at three locations of the Russian Federation: the city of Moscow, the cities of Saratov and Naberezhnye Chelny in the Volga-river area. In addition, data on secular changes of Abkhazian children were analyzed. A large number of anthropometric measurements were taken on each individual including height, weight, arm, leg and trunk lengths (estimated), body diameters and circumferences, skinfold thickness, head and face dimensions. Stages of secondary sex characteristics also were evaluated; data on menarcheal age were collected by status-quo and retrospective methods. Changes in hand grip strength have been evaluated in some of the samples. While stature was increasing during these years, weight, chest circumference and BMI were characterized by negative changes, which became more obvious in elder girls. Changes in handgrip strength also showed negative trends. There were noticeable changes in head and face measurements, which were expressed in more elongated head and face forms, i.e. the head became longer and narrower with narrower and higher faces. Secular changes in head and facial morphology may be considered part of the general trend.

Link

Marital distance and height of children

AJPA DOI: 10.1002/ajpa.21482

Isolation by distance between spouses and its effect on children's growth in height

Sławomir Kozieł et al.

Heterosis is thought to be an important contributor to human growth and development. Marital distance (distance between parental birthplaces) is commonly considered as a factor favoring the occurrence of heterosis and can be used as a proximate measure of its level. The aim of this study is to assess the net effect of expected heterosis resulting from marital migration on the height of offspring, controlling for midparental height and socioeconomic status (SES). Height measurements on 2,675 boys and 2,603 girls ages 6 to 18 years from Ostrowiec Świętokrzyski, Poland were analyzed along with sociodemographic data from their parents. Midparental height was calculated as the average of the reported heights of the parents. Analyses revealed that marital distance, midparental height, and SES had a significant effect on height in boys and girls. The net effect of marital distance was much more marked in boys than girls, whereas other factors showed comparable effects. Marital distance appears to be an independent and important factor influencing the height of offspring. According to the “isolation by distance” hypothesis, greater distance between parental birthplaces may increase heterozygosity, potentially promoting heterosis. We propose that these conditions may result in reduced metabolic costs of growth among the heterozygous individuals.

Link

Hundreds of variants influence human height

From the press release:

An international team of researchers, including a number from the University of North Carolina at Chapel Hill schools of medicine and public health, have discovered hundreds of genes that influence human height.

Their findings confirm that the combination of a large number of genes in any given individual, rather than a simple "tall" gene or "short" gene, helps to determine a person's stature. It also points the way to future studies exploring how these genes combine into biological pathways to impact human growth.

"While we haven't explained all of the heritability of height with this study, we have confidence that these genes play a role in height and now can begin to learn about the pathways in which these genes play a role," said study coauthor Karen L. Mohlke, PhD, associate professor of genetics in the UNC School of Medicine.

...

"These investigators had once been competing with each other to find height genes, but then realized that the next step was to combine their samples and see what else could be found," said Mohlke. "The competitors became collaborators to achieve a common scientific goal."

Large-scale collaborations like this are awesome: people get less credit in a paper with hundreds of co-authors, but they are part of something worthwhile. Plus, it's nice to see a table of authors' different contributions listed in the supplementary material :)

Nature doi:10.1038/nature09410

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Hana Lango Allen et al.

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits1, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait2, 3. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P less than 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Link

Half of hidden heritability found (for height, at least)

This is a quite interesting paper, as it shows, by sampling a large number of individuals), that the heritability of height is not missing after all. The authors looked at a large number of individuals, and this allowed them to discover statitically significant associations between height and more SNPs than before.

This bears great promise as it may hint that genome-wide association studies, that have come under substantial criticism lately, may be failing not because of an inherent flaw, but rather because they are not sampling enough individuals.

The discovered SNPs account for 45% of the heritability of height. Where is the rest? The authors argue for two additional sources:

First, SNPs in current microarray chips sample the genome incompletely. Locations in-between discovered SNPs are in incomplete linkage disequilibrium with the discovered SNPs. So, there is undetected polymorphism, in the gaps between the hundreds of thousands of SNPs in current chips, that may explain a portion of the missing heritability.

Second, SNPs have different minor allele frequencies. For example, in one SNP the minor allele may occur at 10% of individuals, while in others at 30%. This is important, because it is more difficult to arrive at a statistically significant result in the former case.

Consider a SNP with a minor allele frequency of 2%. Then, if you sample 1,000 individuals, only about 20 of them are expected to have the minor allele. You cannot estimate the average height of the minor allele with a sample of 20 people as securely as you can with a sample of 500. Thus, if the SNP influences height in a small way, you will not be able to detect it.

A further complication, which I've written about before, is that some variation in the human genome is family-related, or at least occurs at fewer individuals than the allele frequency cutoff. If 99.9% of people have C at a given location and 0.1% of people have T, this variant is unlikely to be included in a microarray chp, because it is too rare to matter economically: you would only get a handful of individuals -if you're lucky- in a sample of 1,000 for such a variant. However, rarity does not mean that the variant is functionally unimportant, and the rare allele may play a substantial role in the height of the people who possess it.

The publication of this paper is a cause for optimism, as it shows that progress can be made by brute force: fuller genome coverage and more individuals. We'll have to wait and see whether or not the same approach will work for other complex traits, such as IQ or schizophrenia, that have been hitherto difficult to crack.

Obviously, the cost of sampling more individuals will become an issue in future studies, but the cost-per-individual is expected to drop. So, I'm guessing that more discoveries are in store for us in the next few years.

UPDATE (Jun 28):

Not the main point of the paper, but also included in the supplementary material (pdf) are some nice PCA results.

In the European-only PCA we see the familiar north-south gradient (anchored by Tuscans TSI and Netherlands NET on either side), and the orthogonal deviation of the Finns. Swedes (SWE) occupy a northern European end of the spectrum like the Dutch, but are spread towards Finns, reflecting low-level Finnish admixture in that population. Conversely, Finns are variable along the same axis, reflecting variable levels of admixture. Australians (AUS) and UK, on the other hand, are on the northern European edge of the main European gradient, with a number of individuals spread toward the Tuscan side.

The PCA with all populations is also quite interesting. East Eurasians (Chinese and Japanese) form a tight pole at the bottom right. Gujarati Indians (GIH) form a different pole, spread towards Europeans, reflecting variable levels of West Eurasian admixture in that population, probably corresponding to the ANI element recently discovered in Indian populations. Mexicans (MEX) are spread towards East Asians, reflecting their Amerindian admixture, but notice how they are not positioned exactly on the European-East Asian axis, probably reflecting the third, minority, Sub-Saharan element in their ancestry, as well as the fact that Amerindians are not perfectly represented by East Asians. Finns are tilted towards East Asians, as expected, reflecting the fact that their genetic specificity vis a vis Northern Europeans is due to low-level East Eurasian ancestry.

An interesting aspect of the first two PCs is the fact that the Maasai (MKK) and Luhya (LUW) from Kenya are not separated from Caucasoids, and neither are Yoruba from Nigeria (YRI). This is a good reminder of the fact that identity in the first two principal components may mask difference revealed in higher order components. This difference (at least for Maasai) is seen in the next two PCs.

Nature Genetics doi:10.1038/ng.608

Common SNPs explain a large proportion of the heritability for human height

Jian Yang et al.

Abstract

SNPs discovered by genome-wide association studies (GWASs) account for only a small fraction of the genetic variation of complex traits in human populations. Where is the remaining heritability? We estimated the proportion of variance for human height explained by 294,831 SNPs genotyped on 3,925 unrelated individuals using a linear model analysis, and validated the estimation method with simulations based on the observed genotype data. We show that 45% of variance can be explained by considering all SNPs simultaneously. Thus, most of the heritability is not missing but has not previously been detected because the individual effects are too small to pass stringent significance tests. We provide evidence that the remaining heritability is due to incomplete linkage disequilibrium between causal variants and genotyped SNPs, exacerbated by causal variants having lower minor allele frequency than the SNPs explored to date.

Link

Height-IQ-Gender interplay

Am J Psychol. 2009 Winter;122(4):527-36.

The role of height in the sex difference in intelligence.

Kanazawa S, Reyniers DJ.

Recent studies conclude that men on average have higher intelligence than women by 3-5 IQ points. However, the ultimate evolutionary question of why men should have evolved to have higher intelligence than women remains. We suggest that men may have slightly higher intelligence than women through 4 mechanisms: (1) assortative mating of intelligent men and beautiful women, (2) assortative mating of tall men and beautiful women, (3) an extrinsic correlation between height and intelligence produced by Mechanisms 1 and 2, and (4) a higher-than-expected offspring sex ratio (more sons) among tall (and hence intelligent) parents. Consistent with our suggestion, we show that men may have higher IQs than women because they are taller, and once we control for height women have slightly higher IQs than men.The correlation between height and IQ and the female advantage in intelligence persist even after we control for health as a measure of genetic quality, as well as physical attractiveness, age, race, education, and earnings. Height is also strongly associated with intelligence within each sex.

Link

Spouse selection in Sardinia

American Journal of Physical Anthropology doi:10.1002/ajpa.21150

Spouse selection by health status and physical traits. Sardinia, 1856-1925

M. Manfredini et al.

Abstract

Military medical information and data from civil registers of death and marriage have been used to study the role of physical characteristics and health conditions in explaining access to marriage for the male population of Alghero, a small city located in Sardinia Island (Italy), at the turn of 19th century. Literature data about contemporary populations have already demonstrated the influence of somatic traits in the mate choice. The results presented here show that men with low height and poor health status at the age of 20 were negatively selected for marriage. This holds true also in a society where families often arranged marriages for their children. This pattern of male selection on marriage was found to be particularly marked among the richest and wealthiest SES groups. Our hypothesis is that this social group carefully selected for marriage those individuals who were apparently healthier and therefore more likely to guarantee good health status and better life conditions to offspring. In evolutionary terms, the mate choice component of sexual selection suggests that the height of prospective partners could be claimed as one of the determinants, along with other environmental causes, of the observed higher stature of men belonging to the wealthiest social strata of the Alghero population.

Link

Stature evolution in Andaman Islanders

A good related Wired News story on Why Pygmies are Small

CURRENT ANTHROPOLOGY Volume 50, Number 5, October 2009
DOI: 10.1086/605429

Stature, Mortality, and Life History among Indigenous Populations of the Andaman Islands, 1871–1986

J. T. Stock and A. B. Migliano

Despite considerable interest in the evolution of small body size, there is little evidence for changes in body size within small‐bodied human populations. This study combines anthropometric data from a number of studies of the body size of Andaman Islanders from 1871 to 1986. The colonial history of the Andaman Islands is characterized by high rates of mortality among the indigenous populations. However, long‐term conflicts between tribal groups of the Andaman Islands and British and Indian settlers led to some groups being relatively isolated and sheltered from infectious disease and the high rates of mortality that affected other groups. When temporal trends in stature are compared in this context, there is evidence for a reduction in stature among the Great Andamanese who had close contact with the British during the period of highest mortality. Adult stature among the Onge appears to have increased as government involvement diminished following Indian independence. The Jarawa, who had lower rates of mortality throughout the past century, have significantly higher stature than the other groups. These results are interpreted in the context of life‐history theory, adaptation, and plasticity. They provide the first long‐term diachronic evidence for a relationship between mortality and stature among small‐bodied humans.

Link

ASHG 2009 abstracts

It's that time of year again. Here is a list of abstracts from ASHG 2009 that caught my attention in three broad areas. It will be very interesting to see these when they become full papers, but if you are one of the lucky ones that goes to Hawaii this October and want to drop me a line about any of them, feel free to do so!

Population Genetics

Haplogroup H of mitochondrial DNA, a far echo of the West in the heart of Central Asia

Through the millennia, Inner Asia played a pivotal role in shaping the history that greatly added to the cultural, ethnic, and genetic diversity observed throughout present Eurasia. Perhaps the two most significant phenomena witnessed in this part of the world were the ambitious expansion strategy employed by Mongolia’s most prominent personality, Genghis Khan and the complex network known as the Silk Road that for nearly 3,000 years contributed to the exchange of goods and the transmission of philosophy, art, and science that laid the foundation for the great civilizations of China, India, Egypt, Persia, Arabia, and Rome, and in several respects to the modern world. Over the last few years, through an international collaborative effort, researchers at the Sorenson Molecular Genealogy Foundation were able to collect 2,727 DNA samples, informed consents, and genealogical data in Mongolia, Kyrgyzstan, and Kazakhstan. All the samples were sequenced for the three hypervariable segments of the mitochondrial DNA (mtDNA) control region to assess the genetic composition of the modern population of these countries. We identified ~600 different haplotypes that could be ascribed to more than 30 haplogroups and sub-haplogroups. As expected, most haplogroups are typical of modern East Asian populations, but intriguingly, many different Western Eurasian clades were also identified, with a particular high incidence of H (~8.0%), the most common haplogroup in Europe. This feature cannot be attributed to genetic drift since different H sub-lineages have also been identified, each of them represented by several different haplotypes. The mtDNA distribution profile in the heart of Central Asia suggests a direct link between this area and Western Eurasia that could be explained by ancient migrations or by more recent historical events, such as Genghis Khan’s conquering efforts and trade or cultural exchanges along the Silk Route. To discriminate between these two possible scenarios, we are now analyzing a subset of these samples at the highest possible level of resolution - that of complete mtDNA sequences - focusing particularly on those H mtDNAs that seem to be the most informative considering their control-region haplotypes. Our preliminary data seems to be in favor of rather ancient genetic inputs from the West in shaping the peculiar mtDNA gene pool of Inner Asia’s present-day populations.

The following study seems to do precisely what I recently asked for:

However, as the PCA analysis shows, Ashkenazi Jews are distinct from both Europeans and non-Jewish Middle Eastern populations and cannot be viewed as a simple mix of the two; their distinctiveness must be -in part- due to the specific features of the small founder population of that community after it became effectively reproductively semi-isolated from gentiles after Roman times. It would be interesting to see different Jewish communities studied in the context of a broad variety of European and Middle Eastern populations, to determine whether Ashkenazi distinctiveness is specifically Ashkenazi or more generally Jewish distinctiveness; I would bet on a combination of the two.

Abraham's children in the genome era: Major Jewish Diaspora populations comprise distinct genetic clusters with shared Middle Eastern ancestry

Despite residence all over the world, Jewish populations have maintained continuous genetic, cultural, and religious tradition over 4,000 years. The unique ethnic makeup and social practices provide an invaluable opportunity to understand their genetic origins and migrations and to elucidate the genetic basis of complex disorders. To generate a comprehensive HapMap of ethnically diverse, healthy Jewish populations, we used the Affymetrix array 6.0 to genotype 381 samples recruited from 7 Jewish communities with different geographic origins: Eastern European Ashkenazim; Italian, Greek and Turkish Sephardim; Iranian, Iraqi, and Syrian Mizrahim (Middle Easterners). Here, we present population structure results from compiled datasets after merging with the Human Genome Diversity Project and the Population Reference Sample studies, which consisted of 146 non-Jewish Middle Easterners (Druze, Bedouin and Palestinian), 30 northern Africans (Mozabite from Algeria), 1547 Europeans, and 653 individuals from other African, Asian, Latin American, and Oceanian populations. Both principal component analyses and multi-dimensional scaling analysis of pairwise Fst distance show that Jewish populations form a cluster clearly distinct from all major continental populations. The results also reveal a finer population substructure in which each of 7 Jewish populations studied here form distinctive clusters - in each instance within group Fst was smaller than between group, although some groups (Iranian, Iraqi) demonstrated greater within group diversity and even sub-clusters, based on village of origin. By pairwise Fst analysis, the Jewish groups are closest to Southern Europeans (i.e. Tuscan Italians) and to Druze, Bedouins, Palestinians. Interestingly, the distance to the closest Southern European population follows the order from proximal to distal: Ashkenazi, Sephardic, Syrian, Iraqi, and Iranian, which reflects historical admixture with local communities. STRUCTURE results show that the Jewish Diaspora groups all demonstrated Middle Eastern ancestry, but varied significantly in the extent of European admixture. There is almost no European ancestry in Iranian and Iraqi Jews, whereas Syrian, Sephardic, and Ashkenazi Jews have European admixture ranging from 30%~60%. Analysis of identity-by-descent provides further insight on recent and distinct history of such populations. These results demonstrate the shared and distinctive genetic heritage of Jewish Diaspora groups.

So, it seems that there will soon be real genomic data on the source and extent of admixture in Jews. The absence of Greek and Anatolian samples may be problematic in finding the sources of such admixture, but the presence of Tuscans, who are reasonably close to them in a pan-European context should do well to serve as a substitute. In a recent sutdy (in which Anatolians were not included), the closest populations to Ashkenazi Jews were Italians of mostly southern provenance (Fst=0.0040) and Greeks (Fst=0.0042) and fairly close to Tuscans (Fst=0.0066)

The following study seems to demonstrate my recent suggestion of archaic admixture in Africa itself:

It does not, however, tell us that this is because of archaic introgression in Europeans. The culprit could equally well be long-term population structure in Africa, i.e., the presence of "modern" and "archaic" populations in Africa itself.

Deep population structure in sub-Saharan African populations

We analyzed ~500 Kb of resequencing data from 91 different intergenic regions in samples from three sub-Saharan African populations: Mandenka from Senegal, Biaka pygmies from the Central African Republic and San from Namibia. We employed novel methodology to estimate the split times and migration rates between populations. We found strong evidence for split times that predate the exodus of modern humans out of Africa (e.g., > 100 Kya). In addition, we also found evidence of ancient admixture (with unknown ‘archaic’ human groups) in the recent history of both the Biaka and the San.

Analysis of Genomic Admixture in Costa Rica Population

Costa Rica (CR) population is a unique population representing a typical admixture of major continental ancestral populations. 1,301 samples collected from participants in a population-based study conducted in the Guanacaste region of CR were genotyped on a custom Illumina iSelect chip harboring 27,635 SNPs. The SNPs on the chip were selected based on multi-ethnic tagging strategy for three HapMap populations: CEU, YRI and JPT+CHB and cover 1,000 candidate genes/regions for a range of cancers. This data set was sufficiently large for the investigation of population substructure in our CR study and the examination of linkage disequilibrium (LD) patterns. Three HapMap major continental populations and a Native American population from the Illumina iControl DB were used as the reference populations for these analyses. Our preliminary results indicate that the Guanacaste CR population was formed mainly by a three-way admixture with 42.5%, 38.3% and 15.2% Native Indian, European, and African respectively. In addition, 4.0% residual genetic component derived from Asians was observed in our CR samples. Both model based STRUCTURE program and Principal Component Analysis (PCA) revealed consistent substructure pattern for the CR population. The magnitude of LD in the CR population seems to be smaller than all the reference populations except YRI. A more detailed knowledge of the underlying genetic structure of the CR population would be informative to assess its population genetic history and to assist in the interpretation of investigations of complex diseases in the CR or a comparably admixed population.

Analysis of Genetic Substructure of Han Chinese Using Genome-Wide SNP Arrays: Implication for Association Studies.

China will start this year a $30 million effort of genome-wide association studies (GWAS) of common diseases in Chinese populations which have been largely underrepresented in the similar effort worldwide. A general concern is population stratification (ancestry differences) among subpopulations which can cause false positive associations. Han Chinese is the largest ethnic group in the world, however, its population substructures are often expected and yet well characterized. In this study, we examined population substructures in a diverse set of >1,700 Han Chinese samples collected from 26 regions, each genotyped with at least 160K single nucleotide polymorphisms (SNPs). Our results showed that: (a) Han Chinese population is complicatedly substructured, with the main observed clusters roughly corresponding to northern Han, central Han and southern Han; (b) Han Chinese samples collected from large cities, such as Shanghai, Beijing and Guangzhou, show diverse source of ancestries including three aforementioned clusters; (c) HapMap samples (CHB & CHD) and HGDP samples (Han & Han-NChina) deliver a limited representation of Han Chinese people. Building on the above insights, we investigated false positive rates and statistical power in various study designs using both empirical and simulated data. We further explored sample collection strategies and public data usage for future association studies.

It will be interesting to see if the authors of the following study estimated gene flow in non-southern European populations as controls, to see what is the excess of Sub-Saharan admixture detected in the three southern European samples, and exactly what "methods that can infer admixture proportions in the absence of accurate ancestral populations" they used. Hopefully they will also extend their linkage disequilibrium analysis for the other populations besides Spaniards.

Characterizing the history of sub-Saharan African gene flow into southern Europe

Recent analyses of whole-genomeSNP data sets have suggested a history of sub-Saharan African ancestral contribution into southern Europe but not in northern Europe, consistent with previous analyses based on the Ychromosome and mitochondrial DNA. However, there has been no characterization of the proportion of African admixture in southern Europe, or of its date. Here we analyze data from ~450,000 autosomal SNPs in the Population Reference Sample, ~650,000 SNPs from the Human Genome Diversity Panel, and ~1.5 million SNPs from the HapMap Phase 3 Project, and studied patterns of correlation in allele frequencies across populations to confirm the evidence of African ancestry in many southern European populations but not in northern Europeans. Using methods that can infer admixture proportions in the absence of accurate ancestral populations, we estimated that the proportion of sub-Saharan African ancestry in Spain is 2.4 +/- 0.3%, in Tuscany 1.5 +/- 0.3%, and in Greece 1.9 +/- 0.7% (1 standard error). We also studied the decay of admixture linkage disequilibrium with genetic distance, which provided a preliminary estimate of the date of African gene flow into Spain of roughly 60 generations ago, or about 1,700 years ago assuming 28 years per generation. This date is consistent with the historically known movement of individuals of North African ancestry into Spain, although it is possible that this estimate also reflects a wider range of mixture times.

Genome-wide patterns of population structure and admixture among Hispanic/Latino populations

In order to document genome-wide patterns of variation in Hispanics/ Latinos (HL’s) we genotyped individuals from five distinct populations recruited in the US: Mexico, Colombia, Ecuador, Dominican Republic and Puerto Rico. We present population structure results from an extensive genome-wide SNP dataset compiled by merging Affymetrix 500K and Illumina 650K data from these populations together with the Human Genome Diversity Panel, HapMap, Mao et al (2005), and POPRES studies. We apply Principal Component Analysis (PCA) and a clustering method, frappe, to infer admixture and genetic relationships of 262 HL individuals with 467 Africans, 715 Europeans, and 210 Native Americans comprising a total of 88 populations. We observe substructure within Native Americans, and, as expected, find that the admixed HL populations show Native American ancestry derived from local Native American populations. We find striking differences in estimated population-wide mean African, European and Native American ancestry proportions which are consistent with historical admixture and proximity to slave trade routes. The Dominican Republic and Puerto Rico, located on islands along slave trade routes, show high levels of African Ancestry (means 41.7% and 23.6% respectively) with less Native American Ancestry (11.5% and 18.9%). Colombians show a wide range of both African and Native American ancestry, though they have an overall mean of slightly higher Native American ancestry (36.3%) and lower African ancestry (11.7%) than the highly-African Dominicans and Puerto Ricans. Ecuadorians show the highest Native American mean ancestry (54.0%) with low estimated mean African Ancestry (7.3%). Mexico shows the largest range of Native American ancestry (11.0% - 79.0%) with an overall mean of 50.1% Native American ancestry and the lowest African ancestry (5.6%). Our study shows a broad range in admixture proportions across different HL individuals as well as different admixture patterns across populations. We also compare this genotype data with mtDNA and Y chromosome genotypes and use simulations to estimate ancient male and female sex ratios in each HL population. Lastly, we discuss implications of population structure for genome-wide association studies in admixed populations such as HL’s, especially when recruited in the United States.

A new statistical method to infer population admixture events using genetic variation data

We present a novel statistical method that uses densely-spaced Single- Nucleotide-Polymorphism (SNP) data to identify the major admixture events occurring throughout a population’s history. The model has several advantages over leading available analytical approaches in this area, such as principal-components-analysis and STRUCTURE. In particular it can simultaneously (i) take advantage of the information inherent in patterns of linkage disequilibrium, i.e. non-random associations amongst neighbouring SNPs along a chromosome, (ii) efficiently analyse hundreds of individuals at hundreds of thousands of SNPs genome-wide, and (iii) allow for relatively straight-forward interpretation and direct inference of key historical parameters, such as the proportions and times of major admixture events. Using simulated data matched to currently available human datasets, we show that our model can identify and accurately date admixture events that have occurred between 7 and 150 generations ago. As our technique exploits the rich information in genetic data to infer details of a population’s admixture history, it marks a powerful complement to anthropological research and can help to resolve a number of existing controversies. We present results from applications of our model to two datasets: (1) SNP data from 22 distinct genetic regions for individuals from three chimpanzee populations in Africa; (2) genome-wide 650K SNP data for individuals from 53 world-wide populations of the Human Genome Diversity Panel (Science 319, 1100-1104). We highlight a number of intriguing new insights from these analyses. For example, the chimpanzee analysis showcases the model’s ability to infer the relative divergence among populations. The human analysis identifies several important admixture events, some of which are historically wellestablished (e.g. identification of recent European genetic influx into the Maya Native American population), others that can be placed into a clear historical context (e.g. an East Asian genetic influx into several Central and South Asian populations dated precisely to the era of the Mongol empire), and some that are to our knowledge novel (e.g. admixture in the Cambodian population between a Central/South Asian source and an East Asian source dated to around the period of the Cambodian Empire).

Bayesian methods of estimating ancestry using whole-genome SNP data

Estimation of the genetic ancestry of an individual is useful for association studies, disease risk prediction, population genetic analyses and is of inherent interest for the individual themselves. We have investigated methods of estimating ancestry using whole-genome SNP data on each individual. We focus on the scenario where the goal is to determine ancestry in relation to a set of genotype or haplotype data that is available from a set of distinct source populations, for example, the HapMap 2, HapMap 3 or 1000 Genomes datasets. Inference in this setting can focus either on the estimation of global ancestry, in which an overall estimate of the proportion of ancestry from the source populations is needed, or local ancestry, which aims to partition an individual genome into distinct segments of ancestry from the source populations. We have compared 2 models based on the estimated allele frequencies in the source populations at a set of unlinked SNPs. Model 1 only models global admixture, whereas Model 2 models both global and local admixture. Using simulated individuals with differing proportions of CEU and YRI admixture (based on HapMap3 data) we find that there is a relatively small difference in the mean square error of the estimates of global admixture from the 2 methods (1.16 10-4 and 8.88 10- 5 respectively). Since Model 1 is much faster to fit that Model 2 these results suggest that Model 1 can be used to estimate the level of global ancestry, or at the very least will be useful as an initial estimate for use in Model 2. Further investigation is required to see how these results hold for more genetically similar source populations. In contrast, the mean square error for the estimates of local admixture from the 2 methods is 0.298 and 0.0861 respectively, suggesting that an explicit model of local ancestry is needed to carry out this level of inference. We are also investigating the utility and practicality of using linked SNP data to estimate global and local admixture.

A detailed phylogeography of mtDNA haplogroup C1d: another piece in the Native American puzzle

Recent studies based on complete mitochondrial DNA (mtDNA) sequences revealed that two almost concomitant paths of migration from Beringia led to the dispersal of the first Americans (Paleo-Indians) approximately 15-17 thousand years ago (kya). This first expansion was followed by later more restricted diffusion events from the same dynamically changing Beringian source. Thus, five pan-American (A2, B2, C1, D1, and D4h3a) and four geographically confined (D2, D3, X2a, and C4c) mtDNA haplogroups represent the current female legacy of the ancient migratory events that gave rise to the native populations of the double continent. Regarding haplogroup C1, all its members appear to belong to one of three branches: C1b (characterized by the control-region transition at np 493), C1c, and C1d (with the control-region transition at np 16051). These three sub-haplogroups are found throughout the Americas, thus supporting the scenario that they most likely differentiated at the early stages of the Paleo-Indian southward migration. If considered as three separate founders, C1b, C1c, and C1d would bring the currently known number of native pan-American lineages to seven. As a whole, the C1 haplogroup has an estimated age of 17.0- 19.6 ky, while the three individual branches are dated 16.5-17.0 ky, 17.2- 17.6 ky, and 7.6-9.7 ky, respectively. The extremely young age estimate of C1d has been attributed, at least for the moment, to a major underrepresentation of C1d mtDNAs (only nine complete sequences published to date) in the current Native American mtDNA phylogeny. We have addressed this issue in the current study by completely sequencing more than 60 novel mtDNAs belonging to haplogroup C1d, which were carefully selected on the basis of both control-region variation and geographic/ethnic origin. Phylogeographic analyses have provided not only an accurate evaluation of the expansion time of C1d in the Americas, but also a detailed picture of its current distribution in both general mixed and indigenous populations.

Genetic diversity of European population isolates in the context of their geographic neighbors

Mapping traits in population isolates provides an opportunity to simplify the challenges of complex trait mapping because such populations likely have enhanced levels of linkage disequilibrium and reduced genetic heterogeneity for the underlying traits. Here we analyze high-throughput SNP genotyping data to compare genomic-scale patterns of variation in several European population isolates (Adygei, Basque, Orcadian, Roma from Slovakia, Sardinians, and Sorbs) and contrast their patterns of variation to geographical proximal populations. Our results reveal insights for the demographic history of each of these unique populations, suggest substantial variation among these population isolates in patterns of diversity, and highlight the importance of population selection in genome-wide association mapping.

Incompatibility of current Finnish mitochondrial diversity with simulations of assumed settlement history

Traditionally, geneticists studying Finnish population history have assumed a model where Northern and Eastern Finland were mostly uninhabited until the 16th Century A.D. and were then settled by small family groups from South-Western Finland. The reduced genetic diversity and the distinct Finnish disease heritage are seen as consequences of these founder effects. Y-chromosomal diversity is indeed reduced in the present population, especially in the eastern parts of the country. However, mitochondrial diversity is not heavily reduced compared to South-Western Finnish or other European populations. This discrepancy has been explained with the higher mitochondrial mutation rate having restored mitochondrial diversity in these populations since the founder effects.

In our view it seems unlikely that even with high mitochondrial mutation rates mtDNA diversity could be restored over a mere 17 generations after the alleged tight bottlenecks. Archaeological evidence also suggests a different settlement history, e.g. settlement beginning in South-Eastern instead of South-Western Finland.

In this study we use simuPOP, a state-of-the-art forward simulation tool, to simulate datasets corresponding to Finnish mitochondrial diversity under the traditional model and compare them with actual present-day Finnish data. We show that current mitochondrial variation is unlikely under this model, increasing the credibility of alternative hypotheses.

On the borderline between the east and the west: the maternal genetic background of Karelians

Introduction: The frontier between Finland and Russia represents one of the most conspicuous socioeconomic gaps in the world. Based on the mean gross national product, there is a ten-fold difference between Russian Karelian Republic and Finnish Karelia. Otherwise these populations share the same geophysical environment. For these reasons, Karelia has been a very interesting field of research for multifactorial disease studies. However, this area has undergone many demographic incidents, such as wars and famine, which may cause local differences in the gene pool. In this study, we wanted to elucidate the maternal genetic background of Karelians. Materials: Blood samples were collected from healthy unrelated individuals without known foreign background from four Karelian districts; Aunus(n=218), Viena(n= 87), Tver(n=61) and Finnish Karelia (n=70), The sample collection was performed according to the Basic Principles of the Declaration of Helsinki. Methods: The entire mitochondrial DNA was sequenced in 32 reactions per sample with the BigDye® Terminator v3.1 Cycle Sequencing Kit in the Applied Biosystem’s 3730 Genetic Analyzer sequencing machine. Sequence alignments were made by the SeqScape® Software, Version 2.5 (Applied Biosystem). Results: Haplogroup H was very common in all populations. However, H1a is almost absent in Finnish Karelia. Also U and its subhaplogroups were common. Specially U5b1b1 reached over 16% in Viena Karelians. U4 was most common among Tver Karelians. Conclusions: The maternal genetic background seem to be complex in this area. There is clear regional differences. Also there is solid evidence of gene flow from various sources. Representation of the clearly Asian haplogroups is strikingly low.

Genetic Landscape of Eurasia Viewed from Large Allele Frequency Differences.

The diversification leading to modern human populations in Eurasia is one of the most important topics in the study of human expansions after leaving Africa. Most studies of Eurasia populations have used either limited markers or involved insufficient population coverage. We chose 68 markers based on large allele frequency differences among a few Eurasian populations and then typed them on 1766 individuals from 34 populations representing all subdivisions of Eurasia. Analyses using the STRUCTURE program showed a clinal east-west division when K=2, with a median border dividing Central Asia along the Ob River, the Kazakh highland, the western side of Pamir Mountains, and the southwestern side of the Himalayas. We fit curves to the STRUCTURE loadings using distances of the population coordinates from the median border. The genetic structure changed dramatically only within 2000km on each side of the border. At higher values of K the western populations of East Asia are the first to be distinguished (at K=3): Mongols, Tibetans, Qiang, and Baima, are most distinct from the more eastern populations. At K=4 Southwest and South Asians are distinguished from the Europeans; At K=5 Southeast Asians and at K=6 Central Asians are successively distinguished from eastern East Asians. Several more isolated populations such as Samaritans, Atayals, or Micronesians were distinguished in different independent runs when K=7 providing no clear anthropological information. South Asians were always clustered with Southwest Asians with pronounced similarity to Central Asians. The failure to distinguish South Asians maybe due to the selection of the markers with large allele frequency differences specifically between Europeans and East Asians. We also tested for statistical differences in the allele frequencies for all pairs of clusters when K=6. The results showed significant borders (P less than 0.0001) including those between western East Asians and eastern East Asians or Central Asians; however, insignificant borders were observed between Southwest Asians and Southeast Asians or western East Asians, neither was between Central Asians and eastern East Asians. This indicates substantial gene flow in North Asia between eastern East Asians and Central Asians, and in South Asia between South Asians and Southeast Asians. Using increased population and marker coverage, this study helps to understand the details of genetic diversity and landscape of Eurasians.

Anthropometry

Dairy intake associates with the IGF2 rs680 polymorphism to height variation in Greek children. The GENDAI study

Objective: Height is a classic polygenic trait with a number of genes underlyingits variation. We evaluated the prospect of gene to diet interactions ina children cohort for the IGF2 rs680 polymorphism and height variation.Methods: We screened 795 peri-adolescent children (424 females) aged10-11 years old from the (Gene and Diet Attica Investigation; GENDAI)paediatric cohort for the IGF2 rs680 polymorphism. Results: Children homozygousfor common allele (GG) were taller (148.9 ± 7.9 cm) comparing tothose with the A allele (148.1 ± 7.9 cm), after adjusting for age, sex, anddairy intake (β±SE: 2.1± 0.95, p=0.026). A trend for interaction for theIgfrs680xdairy intake is also revealed (p=0.09). Stratification by IGF2 rs680genotype revealed a positive association between dairy products intakeand height only in A allele carriers, adjusted for the same confounders(standardized β=0.111, p=0.014). When dairy intake was classified, basedon the median value, into two equal groups of low (1.9 ± 0.7 servings/day)and high dairy products intake (4.4 ± 1.5 servings/day), it was found thatin A allele children high dairy eaters were significantly taller (p=0.05) comparedwith low dairy eaters (148.8 ± 7.9 cm vs 147.4 ± 7.7 cm respectively,adjusted for age and sex). Conclusion: A higher consumption of dairy productsassociated with increased height depending on the rs680 IGF2 genotype.Thus, exploring height variants and elucidating possible interactionswith environmental factors like diet could help us to design

A Non-synonymous HNF4A Variant is Associated with Glycemia During Pregnancy and Offspring Head Circumference in Populations of European Ancestry in the HAPO Study

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study is a multicenter, international study, which examined the association of maternal glucose levels with fetal growth and outcome in 25,000 pregnant women from multiple ethnic groups to demonstrate a continuous relationship between maternal glucose measures and birth size throughout the range of glucose concentrations. We hypothesize genetic factors contribute to these phenotypes, and examined 1536 fetal and maternal SNPs in 79 candidate loci previously implicated in insulin secretion or sensitivity to determine associations with maternal glycemia and insulin secretion (fasting glucose and Cpeptide and 1-hr glucose from the OGTT) at ~28 weeks gestation and/or offspring size at birth (birth weight, length, head circumference, and sum of skinfolds) for HAPO mothers of European (Belfast and Manchester, UK, and Brisbane and Newcastle, Australia; N=3828) and Asian (Bangkok, Thailand; N=1813) ancestry and their offspring. Associations were assessed through linear regressions with the single trait/outcome under an additive genetic model adjusting for known confounders. Among our strongest signals was rs1800961G>A, which encodes a Thr>Ile amino acid change in exon 4 of HNF4A, recently identified in a GWAS meta-analysis as a variant associated with decreased HDL levels. In the HAPO study, this SNP was strongly associated with increased fetal head circumference (0.5cm [95%CI: 0.3-0.7] per maternal minor allele; P=1.2x10-7) in those of European descent. The maternal minor allele was also weakly associated with 1-hour glucose (4.3mg/dL [95%CI: 0.5-7.9]; P=0.03), birth length (0.7cm [95%CI: 0.2-1.1]; P=0.003), birth weight (52.6g [95%CI: -8.0-113.3]; P=0.09), and sum of skinfolds (0.3cm [95%CI: -0.1-0.6]; P=0.13). This same minor allele in the fetal genome was weakly associated with cord C-peptide (0.1ug/dL [95%CI: 0.01-0.22]; P=0.03), and head circumference (0.2cm [95%CI: -0.1-0.4]; P= 0.08). The same trends were observed among the Thai, although not significantly probably due to a reduction in power from the low risk allele frequency (<2%).>

Selection

In a recent study, Heyer used germline mutation rates to estimate time depth, so I am more inclined to take her dates at face value than in papers which used "evolutionary" rates. It will be interesting to see which Y-chromosome types the authors associates with the both the older and recent expansions.

Super Y-chromosomes in Eurasia and the impact of social selection and Neolithic transition

Some Y-chromosomal haplotypes have been found at unusually high frequenciesin Asian and European human populations. The massive spreadof these lineages has been explained by the impact of social selection i.e.the high reproductive success of some males and their relative/descendantsdue to their high social status. The most well-known examples are the “Khanhaplotype” and the “Manchou haplotype” in Asia, and the U’Neill haplotypein Ireland. But are these frequent haplotypes always associated with recentevents of social selection, or could they be linked to much older processes?To address this question, we have surveyed ~ 3500 males in 97 populationsfrom Turkey to Japan. We have focused on the 12 most frequently representedhaplotypes in Eurasia and tested whether their expansions are linkedto a specific factor such as language or subsistence methods. Our resultsshow that both recent and ancient processes are responsible for the expansionsof these lineages. The recent expansions (2000-3000 years) likely tobe linked to social selection are prevalent in Altaic-speaking and pastoralpopulations. This might indicate a recent cultural change in the social organizationof these populations. The ancient expansions (8000-10000 years)are over-represented in Indo-European speaking and sedentary farmer populations,and are likely to be the result of the Neolithic transition.

Lactase Persistence; Multiple causal mutations in sub-Saharan pastoralists

Background Milk is the primary source of nutrition for newborn mammals, including humans. The majority of human adults, estimated at approximately 65%, are unable to digest lactose (the main carbohydrate in milk) effectively since lactase expression is down-regulated after weaning, as it is in other mammals. In some humans however, lactase expression persists into adulthood (lactase persistence, LP) allowing adult consumption of milk from other species, and the frequencies of this trait vary throughout the world. A C-T SNP -13910 bases upstream from the lactase gene (LCT) is associated with LP in Europe. The -13910*T is rare in milk drinking groups in Africa although two other variants (-13915*G, -14010*C) have been shown previously to be significantly associated with LP and in an accompanying abstract (Ingram et al) we confirm a third locus (-13907*G) and present a fourth candidate SNP. However some LP individuals have also been identified who carry none of these alleles. Aims To examine the distribution across Africa of these and other allelic variants; to examine other regulatory regions in population groups in which enhancer alleles are lacking. Results The geographic and ethnic distribution of -13907*G, -13910*T, -13915*G, -14009*G, and -14010*C in 10 different countries and 15 distinct ethnic groups across Africa (n=1221 individuals) is presented here. Several other variants in this enhancer region are also described here for the first time. These tightly clustered enhancer variants are more frequent in pastoralist milk drinking groups than agriculturalist populations and are associated with several different LCT core haplotypes. Two further candidate regulatory regions have been sequenced in the same populations including a 1000bp region immediately upstream from LCT where novel variants have been found. Conclusions The data support the notion that many different mutations do have a functional role in LP, and that the trait has arisen independently several times, being subject to the positive selection conferred by the increased ability to digest milk lactose by people in pastoralist societies.

Extreme Evolutionary Disparities Seen in Positive Selection Across Seven Complex Diseases

Genome-wide association studies (GWASs) have successfully illuminated disease-associated variation. But whether human evolution is heading towards or away from disease susceptibility remains an open question. We analyzed the seven diseases studied by the Wellcome Trust Control Case Consortium (WTCCC), to calculate the relative selective pressure at every significant loci. Results reveal striking differences between the seven studied diseases. We find evidence of recent positive selection in favor of alleles increasing the risk of Type 1 Diabetes (T1D), Crohn’s Disease (CD), Hypertension (HT), Rheumatoid Arthritis (RA), and Bipolar Disorder (BD). Riskassociated alleles (defined as the allele most strongly associated with disease among associated SNPs) for Type 2 Diabetes (T2D) fall largely within the random neutral region, and Coronary Artery Disease (CAD) shows less positive selection than expected by random. When only protective alleles are considered (defined as the allele least strongly associated with disease among associated SNPs), we find that SNPs only associated with T1D, CD, and RA appear to exhibit significant signatures of positive selection. There is significant asymmetry in the 96 SNPs strongly associated with T1D (pvalue ≤0.005) showing strong signs of positive selection, with 79 SNPs selecting for the risky allele, and only 17 SNPs selecting for the protective allele. Furthermore, selection patterns of Coronary Artery Disease (CAD) fall far below the expected levels of random, implying stable allele frequencies. Results reveal the evolutionary trajectories of T1D and CD favor risk alleles, possibly due to their simultaneous role in protection from infectious diseases. These results inform on current understanding of disease etiology, thus aiding efforts to discover novel approaches to disease treatment and prevention.

Detecting Natural Selection in the Human Genome from Pilot1 Data in the 1000 Genomes Project

Identifying signatures of natural selection in the human genome is of fundamental implication for the study of population evolution and for the biomedical research. The distribution of selection in genome will provide important functional information. Natural selection modify the level of variability within and between populations and shapes the pattern of genetic variations in the genome. Genetic variation in genome is the raw data for detection of natural selection. The 1000 Genomes Project produces whole genome sequencing data and offers a unique and great opportunity to scan the genome for signature of natural selection. Five statistics: Tajima’D, Fu and Li’s F, Achaz’s Y, Fay and Wu’s H and Zeng et al.’s E (based on comparing the site frequency spectrum within population) and Fst statistic (based on the measure of population subdivision) were applied to Pilot 1 data in 1,000 genome project to scan the entire genome for detection of selection, where 344 chromosomes from ASI, CEU and YRI were sequenced. A total of more than 20 million of variant sites, 4.8 millions common in three populations were identified. We calculated seven statistics in 10 kb and 100 kb windows across the genome for each population and obtained their empirical distributions. Results show that two kinds of windows analyses lead to the similar distributions. The proportional rank of the test statistic in a particular window compared with the overall empirical genomic distribution was taken as empirical P-value for that window. We identified 3,046 candidate selection regions in ASI population, 2,015 selection regions in CEU, and 2,204 selection regions in YRI at 5% empirical significance level in 10 kb by five statistics based on differences in frequency spectrum. Among 457 candidate genes of selection reported from PubMed, we detected 102 selection genes in ASI, 53 selection genes in CEU, and 101 selection genes in YRI and 11 selection genes common in three populations by familiar Tajima D test. By comparison we obtained 3.9 million SNPs and the whole genome’s fixation index about 0.10~0.11. By compared with the empirical genome-wide distribution of FST, we identified 5, 278 candidate selection regions at an empirical significance level of 2.5% from each of the 22 autosomal chromosomes. Among 581 identified selection regions by FST which were reported from literatures, we found that 294 selection regions overlap our results.

Genomic Landscape of Positive Natural Selection in North European Populations

Analysing genetic variation of human populations to detect loci that have been affected by positive natural selection is important for understanding adaptive history and phenotypic variation in humans. In this study, we analysed recent positive selection in Northern Europe from genome-wide datasets of 250 000 and 500 000 single nucleotide polymorphisms in a total of over 1000 individuals from Great Britain, Northern Germany, Eastern and Western Finland, and Sweden. Coalescent simulations were used to demonstrate that the integrated haplotype score (iHS) and long-range haplotype (LRH) statistics have sufficient power in genome-wide datasets of different sample sizes and SNP densities. Furthermore, the behavior of the FST statistic in closely related populations was characterized by allele frequency simulations. In the analysis of the North European dataset, dozens of regions in the genome showed strong signs of recent positive selection. Most of these regions have not been discovered in previous scans, and many contain genes with interesting functions (e.g. RAB38, INFG, NOS1AP, and APOE). In the putatively selected regions, we observed a statistically significant overrepresentation of genetic association to complex disease, which emphasizes the importance of the analysis of positive selection in understanding the evolution of human disease. Altogether, this study demonstrates the potential of genome-wide datasets to discover loci that lie behind evolutionary adaptation in different human populations.

Evidence of Indigenous American specific selection in skin pigmentation genes

Recent studies of selection in human pigmentation genes have focused on Old World populations, neglecting the evolutionary changes that have occurred in Indigenous American populations since their migration into the Americas. Previous research shows correlations between Indigenous American ancestry and skin pigmentation variation, suggesting a genetic role in the determination of skin pigmentation among these populations. However, few genes contributing to these differences have been described. To identify genes that may have undergone Indigenous American specific changes, this work examines signatures of selection in 82 pigmentation candidate genes by genotyping 88 indigenous individuals from Central and South America using the Affymetrix Genomewide Human SNP Array 6.0. The resulting 906,600 single nucleotide polymorphisms (SNPs) were surveyed for signatures of selection in the Indigenous American populations compared to the HapMap Phase I populations. Evidence of selection was identified using four measures selected for the complementarity of their approaches, including the reduction in heterozygosity (lnRH), Locus-Specific Branch Length (LSBL), Tajima’s D, and by examination of the haplotype block structure. When computing lnRH and LSBL as well as when examining changes in haplotype frequency, the East Asian and European HapMap populations were included because they are the most closely related populations available. These analyses differentiate the selective changes that appear to be shared among East Asian and Indigenous American populations from those that are unique to the Indigenous American populations. For each test, the top5%of the empirical distribution of results was examined and pigmentation genes falling in this tail of the distribution were considered to show statistically significant evidence of selection. Based on these analyses, 12 genes - ADAM17, POMC, AP3B1,OPRM1, SILV, OCA2/HERC, PLDN, MYO5A, RAB27A, CYP1A2, ATRN, and ASIP - show evidence of selection unique to the Indigenous American populations. Many of these genes have known functional roles in melanogenesis and suggest potential pathways responsible for the observed differences in skin pigmentation between Indigenous American and Old World populations.

Patterns of correlation between genetic ancestry and facial features suggest selection on females is driving differentiation.

Human facial features show extensive variation within and among populations. By investigating the relationship between dimorphism in facial features and genetic ancestry in different populations, we can explore the roles of sexual and natural selection on the human face. We measured sexual dimorphism in facial traits while controlling for the effects of overall size differences and then tested for interactions between sex and genetic ancestry. The study sample consists of 254 subjects (n=170 females, n=84 males), ages 18-35, showing West African and European genetic ancestry sampled in the United States and Brazil. Maximum likelihood genetic ancestry estimates were determined from 176 ancestry informative markers (AIMs), which allowed for the proportional estimation of genetic ancestry from four parental populations (West African, European, East Asian, and Native American). Three-dimensional photographs of faces were acquired using the 3dMDface imaging system (Atlanta, GA). 22 standard anthropometric landmarks were placed on each image and XYZ coordinates were collected. All 231 possible pairwise inter-landmark distances were calculated and then log transformed. Using the pairwise distances, we tested whether some distances were larger in one sex than the other, having taken size into account, in a) African Americans sampled in the United States, b) Brazilians sampled in Brazil, and c) the combined African American and Brazilian sample. We found that several pairwise distances differed between the sexes. For example, the distance from the brow to nasal bridge was found to be more than 5% larger in females than males. We then tested for an interaction between sex and genetic ancestry by testing for differences in the slopes of the ancestry association between males and females. Although the pattern differed slightly between samples, after Bonferroni correction many correlations were the found to be same in both sexes. However, females in all three samples had many additional significant correlations that were not seen in males, while males had very few correlations that were not found in females. The results of these analyses suggest that selection on females is driving the differentiation in facial features among populations.

Effect of natural selection on North Asian mitochondrial haplogroup variation

The human mtDNA exhibits striking, region-specific sequence variation. The regional distribution of mtDNA haplogroups have attributed either to genetic drift assisted by purifying selection (Elson et al., 2004; Kivisild et al., 2006; Ingman, Gyllensten, 2007) or to an adaptation to different climates (Mishmar et al., 2003; Ruiz-Pesini et al., 2004). In an attempt to study the mode of selection in mtDNA variation in human populations we sequenced and analyzed 211 complete mtDNA sequences belonging to haplogroups A, C and D accounting in total for 49.3% of mtDNA lineages in North Asia. The North Asian haplogroups A, C and D showed a highly significant deviation from the standard neutral model as well as a bell-shaped distribution of pairwise differences consistent with rapid population expansion. To determine the overall importance of selection in shaping human mtDNA variation we calculated Ka/Ks ratio both for aggregated mtDNAs and for 13 proteinencoding genes within particular haplogroups (A, C and D). We have found a prevalence of Ks over Ka within haplogroups A, C and D indicating the influence of negative selection on mtDNA during evolution. Consistent with some previous reports we have found the Ka/Ks ratio for the ATP6 gene to be the highest among the North Asian sequences suggesting thereby that this gene has been subject to positive selection. We have also observed a set of genes with a somewhat higher Ka/Ks ratio relative to other mitochondrial genes - CO2 for haplogroup A, ND3 and ND4 for haplogroup C. Meanwhile the other approach taking into account the difference in NS/S ratios between the haplogroup-associated and private substitutions (Elson et al., 2004) shows the significant departures from neutrality only for haplogroup D and its subhaplogroup D4. Furthermore single gene analysis reveals the relatively strong influence of negative selection only in CYTb gene within haplogroupD(p=0.011, NI=14.1). In general, our results indicate that there is an evidence for both gene-specific and lineage-specific variation in selection acting on North Asian mtDNAs.

Selection for blue eyes in Europe and light skin pigmentation in East Asia at OCA2/HERC2

OCA2 and HERC2 are two genes on chromosome 15 separated by lessthan 10 kb. Mutations in this region have been shown to have an effect onpigmentation including causing oculocutaneous albinism type 2. In Europeans,a three SNP haplotype (rs4778138, rs4778241, rs7495174) and threeindividual SNPs (rs12913832, rs916977, rs1667394) have been associatedwith blue eyes. We have labeled the three SNP haplotype BEH1. We foundthat the first individual SNP, rs12913832, was in near complete LD withanother SNP (rs1129038). Wetreat these two SNPs together as a haplotype,BEH2. We also found that the other two individual SNPs were actually innear complete LD with each other and decided to label them BEH3. In EastAsians, a SNP (rs1800414) has been identified that is associated with alight skin pigmentation phenotype. We typed these eight SNPs in 64-70population samples. We then examined worldwide distribution of the fourpigmentation alleles. We saw that the light skin allele was at its highestfrequency in eastern East Asia, at midrange frequencies in Southeast Asia,and at lower frequencies in western East Asia. It is virtually absent from therest of the world. BEH1 and BEH3 show very similar global patterns, lowfrequencies to midrange frequencies in Africa and East Asia, midrangefrequencies in India and Eastern Siberia, and midrange to high frequenciesin Southwest Asia, Europe, Western Siberia, the Pacific Islands, and theAmericas. BEH2 shows a different pattern from the other two. It showslow frequencies in East Africa, India, Eastern Siberia, and the Americas,midrange frequencies in Southwest Asians and Southern Europeans, andhigh frequencies in Eastern and Northwestern Europe and Western Siberia.We then typed additional SNPs and test each pigmentation allele for selectionusing the Relative Extended Haplotype Homozygosity (REHH) test. Wefound that the light skin allele of rs1800414 is under selection in East Asiaand that the blue eye allele of BEH2 is under selection in Europe andSouthwest Asia. We show light skin pigmentation has been selected for inEast Asia. This is likely due to lower UV exposure at the higher latitudes(compared to equatorial Africa) and the need for lighter skin for vitamin Dproduction. We also show that blue eyes are selected for in Europe. Thisis most likely due to sexual selection, though another unknown effect of thisparticular allele could be selected for and the blues eyes are a side effect.

Ancestry variation along the genome in Latin American populations and implications for recent natural selection

Latin American populations stem from the admixture starting about 500 years ago of Europeans, Africans and Native Americans. Extreme deviation in ancestry estimates at certain genome locations (relative to the genomewide average) could reflect the action of recent natural selection. We evaluated the distribution of ancestry estimates along the genome using 678 microsatellite markers in 249 individuals sampled from 13 admixed populations across Latin America. We found a significant deviation in ancestry at two genomic locations with more than four times standard deviations from the genome-wide mean: an excess of European ancestry at 14q32 (Zscore = 4.14), and an excess of African ancestry at 6p22 (Z-score = 4.71). These deviations in ancestry were observed in the analysis of the combined dataset as well as in most of the individual populations examined. We showed that our findings are robust to the Native American ancestry populations used. We discussed the implications for recent natural selection in the context of the unique history of the New World, as well as the possibility of artifacts.