Remedial population genetics for Greg Cochran

From Graham Coop's population genetics notes:

1.4 Inbreeding

We can define an inbred individual as an individual whose parents are more closely related to each other than two random individuals drawn from some reference population. [. . .]

1.6 Summarizing population structure

We defined inbreeding as having parents that are more closely related to each other than two individuals drawn at random from some reference population. The question that natu- rally arises is: Which reference population should we use? While I might not look inbred in comparison to allele frequencies in the United Kingdom (UK), where I am from, my parents certainly are not two individuals drawn at random from the world-wide population. If we estimated my inbreeding coefficient F using allele frequencies within the UK, it would be close to zero, but would likely be larger if we used world-wide frequencies. This is because there is a somewhat lower level of expected heterozygosity within the UK than in the human population across the world as a whole.

Wright (1943, 1951) developed a set of ‘F-statistics’ (also called ‘fixation indices’) that formalize the idea of inbreeding with respect to different levels of population structure. He defined F XY as the correlation between random gametes, drawn from the same level X, relative to level Y.

[. . .] the reduction in heterozygosity within individuals compared to that expected in the total population can be decomposed to the reduction in heterozygosity of individuals com- pared to the subpopulation, and the reduction in heterozygosity from the total population to that in the subpopulation.

Jeb Bush and G.W. Bush have more non-New England than New England ancestry

Prompted by a troll post at Sailer's, I did a quick tally of the regional ancestries of Jeb's and G.W.'s great, great, great-grandparents (while I started with 3g-grandparents, I looked farther back wherever possible to identify any likely New England ancestry). The numbers I come up with:

• New England: 10.125 / 32 = 31.64%
• Mid-Atlantic: 11.375 / 32 = 35.55%
• South: 7 / 32 = 21.88%
• Germany: 2 / 32 = 6.25%
• Britain: 1.5 / 32 = 4.69%

Less than a third of Jeb's ancestry actually traces back to New England. You can see the table of Bush ancestors I used here, and see to which region I assigned each of the the 3g-grandparents below the fold (in most cases I chose to count Maryland as Southern; but where Maryland ancestry was mixed with Pennsylvania ancestry I counted it as mid-Atlantic).

While the Bushes represent the very epitome of hated Yankee/Puritan for many anti-New England types, they in fact have twice as much non-New England as New England ancestry.

"American Nations" and magical thinking

Vanishing American, in a longer post, which I highly recommend reading and which I'll probably write more about later, notes:

This whole notion of cultural DNA being passed on from long-ago departed former inhabitants of a place sounds a bit like the popular superstition that ghosts of long-past eras hang around their former home and ''possess'' the people who later inhabit their haunted territory. So if I understand it right, the WASPs and Puritans of old New England are now possessing the bodies of all the diversities who live in Boston and New Haven or Manchester, N.H., and maybe even those Somalis that live in Lewiston, Maine.

I found this observation amusingly apt, having just finished listening to an interview with Colin Woodard in which the following exchange occurs (around 39 minutes into this podcast):

Host: One of the big fears in many countries is how immigration will change the very nature of a city or a state or a place and what's interesting from what you're saying is actually you can be a little more relaxed about that because there's something almost secretive, deep-rooted, almost magical, you can't quite explain it logically that lives on generation to generation, that if you have a sensible immigration policy actually the people who come will be pulled into that story as well, because as you've said before when you go back to look at some of these communities the people for example in New York who trace their roots back to being Dutch is minimal but something from that settlement still affects New Yorkers.

Woodard: You are correct, in that in theory in any country or place in the world if one moves there you would assimilate maybe you personally wouldn't fully successfully do it because you'll always be a foreigner maybe in your own mind or can't master the language completely. But your children will and your grandchildren almost certainly will, if there aren't cultural impediments to being assimilated or allowed to assimilate.

Ancestry of author Colin Woodard

It seems some people have the impression that American Nations-author and JayMan's hero Colin Woodard is some sort of archetypal, Puritan-descended New England Yankee. Instead, Woodard simply provides another illustration of the fact that New England residents today derive the bulk of their ancestry from sources other than New England Puritans.

Woodard's mother has a common name, and I was unable to immediately identify her parents or birth place. I did easily identify the ancestor's of Woodard's father going back a few generations.

While Colin Woodard describes himself as a native of Maine, his father (who has an MA in Creative Writing from Syracuse and now teaches introductory English at the University of Maine Augusta) was born in Los Angeles, and his father's parents were born in Montana (the mother being of 100% Irish Catholic ancestry, as far as I can tell).

Of his father's great-grandparents:

• Only three were born in America (according to census documents, one was born in Michigan, with parents also born in Michigan, and two were born in New York, with parents also born in New York).
• Four were born in Ireland (and evidently Catholic).
• One was born in Quebec (with, going by names, a French Canadian father and Irish Catholic mother).

So Colin Woodard's father is something like 9/16 Irish Catholic, 1/16 French Canadian, and no more than 3/8 colonial American (and it's unlikely the entirety of the American ancestry traces back to New England).

---

After writing the above, I checked one last time for any information on Colin's mother ancestry, and came across this article from Woodard himself. In addition to confirming parts of his paternal ancestry:

My Irish-Catholic great-grandparents worked the iron and copper mines of the interior West, and their children grew up to be Far Westerners. My great-great-great grandmother’s family fled from the same part of Ireland as their future cousins-in-law, but the mines where they found work happened to be in Quebec, so their descendants grew up speaking French and traveling on aboriginal snowshoes.

Woodard mentions:

Life in North America has been immeasurably enriched by the many cultures and people who settled there. I personally celebrate the continent’s diversity, but I also know that my great-grandfather’s people in western Iowa -- Lutheran farmers from the island of Funen in Denmark -- assimilated into the dominant culture of the Midlands (think, for now, “Midwest”), even as they contributed to its evolution.

Which provides evidence of non-New England (and non-colonial American) ancestry on his mother's side, as well. Whatever is responsible for Woodard's leftism, it's fairly safe to say it's not Puritan genes.

Kinship coefficients and Ethnic Genetic Interests (JayMan embarrassing himself again)

Contra the White Nationalists, there’s no such thing as “ethnic genetic interests.”

JayMan supports the above JayMan assertion by linking to another JayMan comment, which sees JayMan copy-and-pasting from Wikipedia a table of inbreeding coefficients by degree of relationship, and asserting the table:

…demonstrates why “ethnic genetic interests” do not exist.

Let that sink in. "HBD" hobbyist JayMan sees coefficients of relationship near zero, and asserts (without being fully aware of what he's asserting) that this means I don't share any particular genetic relatedness with my third cousin relative to a tribesman from New Guinea or a triracial from Jamaica.

This is of course not what an inbreeding coefficient near zero indicates:

The solution to the problem posed in Figure 5.1 will be easy if we can calculate the inbreeding coefficient f H of individual H. The inbreeding coefficient of an individual is the probability that the two gene copies present at a locus in that individual are identical by descent, relative to an appropriate base population. Two genes are identical by descent if, and only if, they are descended from the same individual gene copy. Now of course we must stop somewhere as we trace back the ancestry of the two genes. Otherwise any two gene copies would be certain of being identical by descent, provided that life has a monophyletic origin. The function of the base population is to set the context of the problem. In the base population, all gene copies are assumed not to be identical by descent. [Joe Felsenstein. Theoretical Evolutionary Genetics.]

I'm not much more closely related to my third cousin than to a random member of the approximately-random-breeding population from which we both spring. I am genetically markedly more similar to my third cousin (and any other Northwestern European) than I am to someone like JayMan. This is the essence of "ethnic genetic interests".

From Henry Harpending's appendix to Frank Salter's book:

The coefficient of kinship between two diploid organisms describes their overall genetic similarity to each other relative to some base population. For example, kinship between parent and offspring of 1/4 describes gene sharing in excess of random sharing in a random mating population. In a subdivided population the statistic Fst describes gene sharing within subdivisions in the same way. Since Fst among human populations on a world scale is reliably 10 to 15%, kinship between two individuals of the same human population is equivalent to kinship between grandparent and grandchild or between half siblings. The widespread assertion that this is small and insignificant should be reexamined.

Note also that debates about group selection ultimately have no bearing on the reality of ethnic genetic interests, the existence of which is inarguable. When people from the population I belong to are replaced with members of genetically distant populations, this represents a loss of inclusive fitness for me, and one I see no reason to tolerate, irrespective of how strongly selection has operated at the level of groups in the past.

Massive migration from the steppe is a source for Indo-European languages in Europe

New preprint confirming what those of us who were paying attention were able to infer years ago:

We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost four hundred thousand polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that the populations of western and far eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, ~8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary, and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a ~24,000 year old Siberian6. By ~6,000-5,000 years ago, a resurgence of hunter-gatherer ancestry had occurred throughout much of Europe, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but from a population of Near Eastern ancestry. Western and Eastern Europe came into contact ~4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced ~3/4 of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least ~3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for the theory of a steppe origin of at least some of the Indo-European languages of Europe. [. . .]

R1a and R1b are the most common haplogroups in many European populations today 18,19 , and our results suggest that they spread into Europe from the East after 3,000 BCE. Two hunter-gatherers from Russia included in our study belonged to R1a (Karelia) and R1b (Samara), the earliest documented ancient samples of either haplogroup discovered to date. These two hunter-gatherers did not belong to the derived lineages M417 within R1a and M269 within R1b that are predominant in Europeans today 18,19 , but all 7 Yamnaya males did belong to the M269 subclade 18 of haplogroup R1b.

Ethnic origins of Sony Pictures leadership

Hacked documents reveal a Hollywood studio’s stunning gender and race gap:

One other observation to make about Sony Pictures’ top-paid executives is that they’re almost entirely white. From some quick Internet searching, fifteen of the seventeen appear to be Caucasian, one (Dwight R. Caines) appears to be African-American, and one (Man Jit Singh) appears to be South Asian. (I’ll update these numbers when and if I hear back from Sony Pictures.) In other words, unless I’m missing something, the upper pay echelon of Sony Pictures is 94 percent male, and 88 percent white. [. . .]

Sony Pictures isn’t alone in having a predominantly white, predominantly male leadership, or paying its top executives multiples of what other employees make. But the numbers leaked in the recent hack – assuming they’re accurate – would mean that the top ranks of one major Hollywood studio are perhaps even less diverse than those of Silicon Valley tech companies and large Wall Street banks. After it patches up its security measures, that’s another problem Sony Pictures may have to reckon with.

To point out the obvious, there's one group overrepresented to a much greater degree than "whites" on this list. By my count, 4 out of 4 of the most highly paid are Jewish, and, looking at the full list, 9 out of the 15 "whites" are known to be Jewish or have distinctively Jewish names (Lynton, Pascal, Mosko, Belgrad, Erlicht, Kaplan, Osher, Weiser, Bersch). In addition, Michael De Luca is half Jewish; based on his physical appearance, Michael Barker is almost certainly Jewish; and I have not investigated the ancestry of the four remaining whites on the list (Clinton Culpepper, Zackary Van Amburg, Tom Bernard, and Michael Pavlic). Jews are overrepresented relative to their share in the US population by at least an order of magnitude. Members of the Northwestern European American majority are massively underrepresented. How does Kevin Roose propose Sony Pictures "reckon with" this problem?

Ust'-Ishim: Ancient DNA offers the first of what I expect in the coming years will be many disappointments to those emotionally invested in a SE Asian origin for K-M526

It's been asserted, on crude phylogeographic grounds, that K-M526 originated in South East Asia. A SE Asian origin for K-M526 is credible if you ignore the rest of the Y phylogeny, starting with K-M9, and all other available information. Sadly for Hector, reality, with this recent publication, has again chosen to side with "Eurocentrists".

I don't expect the Hectors will gracefully accept their beating, but to others the presence of a previously unknown branch of K(xLT) in Siberia 45,000 years ago should be a pretty clear signal that the idea of a 500 year sprint from West or Central Asia to an already-inhabited SE Asia, followed, after an indefinite pause, by a repopulating of the world from Sundaland (if not the islands of Wallacea), all while failing to carry any trace of Denisovan admixture back to the future civilized world is an unnecessary and improbable fantasy.

The cline of Denisovan admixture, from faint, highly-selected remnants in mainland SE Asia to maxima among Melanesians and Australian Aborigines, has always pointed to gene flow into the region after its initial settlement rather than out of it, the K-bearers being one obvious candidate for the major source of this dilution. I'd also say it's more likely than not that they (an M526-carrying population of Central Asian origin) are the ones who brought culture to Hector's ancestors.

EthnicMuse's race and testosterone "meta-analysis"

A commenter asks:

What do you think of this website and his analysis of testosterone levels in different racial groups?

https://ethnicmuse.wordpress.com/tag/testosterone/

"EthnicMuse" is attempting to aggregate numbers that can't be aggregated, and the results lack face validity. T levels as measured by different techniques and/or at different laboratories are not in general directly intercomparable.

Clinicians are being presented with normal male reference ranges for serum T from these automated platforms that have low end clinical limits down to 170–200 ng/dl (5.9–6.9 nmol/liter) and upper range limits of 700–800 ng/dl (24.3– 27.7 nmol/liter). These stated reference ranges provided by the manufacturer are significantly lower than the 300-1000 ng/dl (10.4–34.7 nmol/liter) reference range referred to in numerous publications over the past 30 yr based on tradi- tional RIA methods with or without the chromatography step as well as some research techniques employed by in- ternal recovery standards to correct for procedural losses (5).

External quality control programs such as that provided by the College of American Pathologists allow laboratories to compare results with other laboratories using the same method or kit reagents. As shown in Table 1, the median value of a quality control sample (Y-04,2002) varied between 215 and 348 ng/dl (7.5 and 12.0 nmol/liter) among methods with coefficients of variation among laboratories using the same method or instrument ranging between 5.1% and 22.7%. The median average for this sample from all methods was 297 ng/dl (10.3 nmol/liter) and results were as low as 160 or as high as 508 ng/dl (5.5 to 17.6 nmol/liter). These results span the hypogonadal to eugonadal range.

[Measurement of Total Serum Testosterone in Adult Men: Comparison of Current Laboratory Methods Versus Liquid Chromatography-Tandem Mass Spectrometry]

Differences that are to be expected between different assays and different laboratories, apart from any other factors, would likely swamp any anticipated racial differences in circulating testosterone levels. Between-study differences in collection times, sample handling, age and health condition of subjects, and so on, add further noise.

I see that EM is at least vaguely aware of these issues, but he rationalizes publishing his "meta-analysis" as follows:

One cannot and should not compare different testosterone studies with different measurement methods. However, for the race-realist purpose of aggregating data, there is nothing inherently wrong with what the PDF file lists. If JP Rushton can use a few studies and make wild claims which are then used by the Internet-o-sphere, using 150 independent peer-reviewed sources with large samples is much more scientific than anything similar from the race realist community. [. . .]

Age differences will affect the results but healthy males should have negligible decreases. Assuming a 0.4% annual decline from 5000 pg/ml after age 40, a man at 80 should have 4275 pg/mL, less than a 15% difference if my spreadsheet math is correct. It would have been better to normalize for age. So while the tabled rankings is flawed, the point is that the entire issue is flawed as there is no standard measuring method in the first place. That race realists routinely use flawed data should be the issue but …

That blindly aggregating data from disparate studies (which in this realm I've never seen anyone other than EM attempt) is nonsensical does not mean all attempts at comparing circulating testosterone levels between races are "flawed". It means that if one wants to attempt such comparisons, one should focus on studies in which a single set of researchers, using standardized methods, publish results for multiple ethnic groups.

EM is aware, for example, of a study (pdf) in which blood samples from Swedes and Koreans "were analyzed in the same laboratory using the same assay". The result (in EM's words): "the Swedes had 25% more T than the Koreans in this study". I've seen other studies showing lower or similar levels of testosterone in East Asians compared to whites (and none showing anything like the 10% higher testosterone in East Asians asserted by EM). But EM apparently did not like where the data pointed (thus his version of "meta-analysis", in which valid data is swamped with garbage).

Investigating Population History Using Temporal Genetic Differentiation

Investigating Population History Using Temporal Genetic Differentiation

The rapid advance of sequencing technology, coupled with improvements in molecular methods for obtaining genetic data from ancient sources, holds the promise of producing a wealth of genomic data from time-separated individuals. However, the population-genetic properties of time-structured samples have not been extensively explored. Here, we consider the implications of temporal sampling for analyses of genetic differentiation and use a temporal coalescent framework to show that complex historical events such as size reductions, population replacements, and transient genetic barriers between populations leave a footprint of genetic differentiation that can be traced through history using temporal samples. Our results emphasize explicit consideration of the temporal structure when making inferences and indicate that genomic data from ancient individuals will greatly increase our ability to reconstruct population history.

Demography and the Age of Rare Variants

Demography and the Age of Rare Variants

In this paper we describe a method for estimating the age of rare genetic variants. These ages are highly informative about the extent and dates of connections between populations. Variants in closely related populations generally arose more recently than variants of the same frequency in more diverged populations. Therefore, comparing the ages of variants shared across different populations allows us to infer the dates of demographic events like population splits and bottlenecks. We also see that rare functional variants shared within populations tend to have more recent origins than nonfunctional variants, which is consistent with the effects of natural selection.

"25% of the variance in gene expression is due to population differences"

Transcriptome Sequencing from Diverse Human Populations Reveals Differentiated Regulatory Architecture

To better understand the spectrum of gene expression variation, alternative splicing, and the population genetics of regulatory variation in humans, we have sequenced the genomes, exomes, and transcriptomes of EBV transformed lymphoblastoid cell lines derived from 45 individuals in the Human Genome Diversity Panel (HGDP). The populations sampled span the geographic breadth of human migration history and include Namibian San, Mbuti Pygmies of the Democratic Republic of Congo, Algerian Mozabites, Pathan of Pakistan, Cambodians of East Asia, Yakut of Siberia, and Mayans of Mexico. We discover that approximately 25.0% of the variation in gene expression found amongst individuals can be attributed to population differences. However, we find few genes that are systematically differentially expressed among populations. Of this population-specific variation, 75.5% is due to expression rather than splicing variability, and we find few genes with strong evidence for differential splicing across populations. Allelic expression analyses indicate that previously mapped common regulatory variants identified in eight populations from the International Haplotype Map Phase 3 project have similar effects in our seven sampled HGDP populations, suggesting that the cellular effects of common variants are shared across diverse populations.

Testosterone and intergroup competition

Does Competition Really Bring Out the Worst? Testosterone, Social Distance and Inter-Male Competition Shape Parochial Altruism in Human Males

Parochial altruism, defined as increased ingroup favoritism and heightened outgroup hostility, is a widespread feature of human societies that affects altruistic cooperation and punishment behavior, particularly in intergroup conflicts. Humans tend to protect fellow group members and fight against outsiders, even at substantial costs for themselves. Testosterone modulates responses to competition and social threat, but its exact role in the context of parochial altruism remains controversial. Here, we investigated how testosterone influences altruistic punishment tendencies in the presence of an intergroup competition. Fifty male soccer fans played an ultimatum game (UG), in which they faced anonymous proposers that could either be a fan of the same soccer team (ingroup) or were fans of other teams (outgroups) that differed in the degree of social distance and enmity to the ingroup. The UG was played in two contexts with varying degrees of intergroup rivalry. Our data show that unfair offers were rejected more frequently than fair proposals and the frequency of altruistic punishment increased with increasing social distance to the outgroups. Adding an intergroup competition led to a further escalation of outgroup hostility and reduced punishment of unfair ingroup members. High testosterone levels were associated with a relatively increased ingroup favoritism and also a change towards enhanced outgroup hostility in the intergroup competition. High testosterone concentrations further predicted increased proposer generosity in interactions with the ingroup. Altogether, a significant relation between testosterone and parochial altruism could be demonstrated, but only in the presence of an intergroup competition. In human males, testosterone may promote group coherence in the face of external threat, even against the urge to selfishly maximize personal reward. In that way, our observation refutes the view that testosterone generally promotes antisocial behaviors and aggressive responses, but underlines its rather specific role in the fine-tuning of male social cognition.

Physical attractiveness as a phenotypic marker of health

Physical attractiveness as a phenotypic marker of health: an assessment using a nationally representative sample of American adults

Evolutionary explanations regarding the differential preference for particular traits hold that preferences arose due to traits’ association with increased potential for reproductive fitness. Assessments of physical attractiveness have been shown to be related to perceived and measured levels of health, an important fitness-related trait. Despite the robust association between physical attractiveness and health observed in the extant literature, a number of theoretical and methodological concerns remain. Specifically, the research in this area possesses a lack of specificity in terms of measures of health, a reliance on artificial social interactions in assessing physical attractiveness, a relatively infrequent use of non-student samples, and has left unaddressed the confounding effects of raters of attractiveness. Using these concerns as a springboard, the current study employed data from the National Longitudinal Study for Adolescent Health (N ≈ 15,000; aged 25 to 34 years) to assess the relationship between physical attractiveness and various specific and overall measures of health. Logistic and OLS regression models illustrated a robust association between physical attractiveness and various measures of health, controlling for a variety of confounding factors. In sum, the more attractive a respondent was rated, the less likely he or she was to report being diagnosed with a wide range of chronic diseases and neuropsychological disorders. Importantly, this finding was observed for both sexes. These analyses provide further support for physical attractiveness as a phenotypic marker of health. The findings are discussed in reference to evolutionary theory and the limitations of the study and future research suggestions are also addressed.

"Monkeys' faces evolved to avoid crossbreeding"

BBC: Guenon monkeys' colourful and varied faces have evolved as a way to avoid crossbreeding, scientists have found.

Dr James Higham, senior author, said: "Evolution produces adaptations that help animals thrive in a particular environment, and over time these adaptations lead to the evolution of new species.

"A key question is what mechanisms keep closely related species that overlap geographically from interbreeding, so that they are maintained as separate species.

"Our findings offer evidence for the use of visual signals to help ensure species recognition: species may evolve to look distinct specifically from the other species they are at risk of interbreeding with," Dr Higham said.

"In other words, how you end up looking is a function of how those around you look. With the primates we studied, this has a purpose: to strengthen reproductive isolation between populations."

SMBE 2014: more (several dozen) abstracts touching on recent evolution in humans

Detecting patterns of global and local positive selection by examining novel variants in the exomes of 7 world-wide human populations

Laura Botigué ¹, Jeff Kidd², Brenna Henn^1
1Stony Brook University, Stony Brook, New York, USA, ²University of Michigan, Ann Arbor, Michigan, USA

Recent efforts to identify adaptive loci in humans relied primarily on single nucleotide polymorphism array data. For many global populations however, these datasets suffered from ascertainment bias and did not allow for the identification of novel, adaptive variants unique to different populations. In this study we use high coverage exomes and low coverage full genomes from over 50 individuals from 7 human populations of geographically divergent groups from Namibia, Congo, Algeria, Pakistan, Cambodia, Siberia and Mexico to differentiate between local and global adaptation. We additionally apply the same approach to examining 1000 Genomes data. In order to minimize the effect of demography, we compare the site frequency spectrum of putatively functional variants with the neutral site frequency spectrum as estimated from synonymous sites or intergenic loci. We specifically hypothesize that derived variants with a large predicted functional impact found at high frequencies are not deleterious and potentially beneficial. We further hypothesize that derived variants common across populations are good candidates for adaptative traits common to the human species, whereas variants that are at high frequency but population specific are indicative of local adaptation. When we consider only variants with an extreme functional effect, as predicted by GERP scores, a total of 6% are shared across all populations, and 16% are private to a given population at frequencies higher than 10%. We obtain a subset of candidate genes under selection based on these hypotheses and assess common features among then using gene ontology. Overall, results may shed light to human adaptation at the species level, as well as the local level, and finally have a better understanding of how exposure to new environmental pressures affected early human expansion across the globe.

Inference of local ancestry in archaic-modern human admixture and its impact on modern human evolution

Sriram Sankararaman ^{1 ,2}, Swapan Mallick^{1 ,2}, Michael Danneman³, Kay Prufer³, Janet Kelso³, Svante Paabo³, Nick Patterson^{1 ,2}, David Reich^{1 ,2
1}Harvard Medical School, Boston, USA, ²Broad Institute, Cambridge, USA, ³Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany

Analysis of archaic genomes has documented several examples of admixture between archaic and modern human groups e.g. these analyses have revealed that Neandertals interbred with the ancestors of all non-Africans and the Denisovans interbred with the ancestors of present-day Melanesians.  To understand how these admixture events shaped the evolution of modern humans, we need to build maps of archaic ancestry in modern humans.

As a first step, we have developed a statistical method for inferring segments of Neandertal local ancestry in modern humans and applied this method to construct a map of Neandertal ancestry in modern non-Africans, using data from Phase 1 of the 1000 genomes project combined with a high coverage (50×) Neandertal genome.  This map reveals the adaptive impact of Neandertal gene flow as we find enhanced Neandertal ancestry in genes involved in keratin filament formation as well as other biological pathways.  We also observe large regions with reduced Neandertal ancestry consistent with purifying selection against introgressing Neandertal alleles in part due to these alleles contributing to hybrid male sterility.
To extend this approach to other archaic-modern human introgression events, we generated deep genome sequences of 21 people from populations with substantial Denisovan ancestry: 16 Papua New Guineans, 2 Bougainville Islanders, and 3 aboriginal individuals from Australia. We also extend our method to infer Neandertal and Denisovan local ancestry in these populations. We test whether the same evidence for hybrid male sterility is observed in this introgression event as is observed between Neandertals and modern humans.

SMBE 2014: Insights on Sexually Antagonistic Selection in the Human Genome

Insights on Sexually Antagonistic Selection in the Human Genome

Elise Lucotte ¹, Romain Laurent^{1 ,2}, Laure Segurel¹, Evelyne Heyer¹, Bruno Toupance^1
1Eco-anthropologie et Ethnobiologie, UMR 7206 CNRS, MNHN, Univ Paris Diderot, Sorbonne Paris Cité, F-75005, Paris, France, ²Max Planck Institute for Evolutionary Anthropology, Department of Evolutionary Genetics, Leipzig, Germany

In species with two separate sexes, sexually antagonistic (SA) selection occurs if both sexes undergo selection in opposite direction for a trait. If this trait is coded by the same set of genes in both sexes, an intralocus sexual conflict (IASC) arises. These conflicts initiate the evolution of sexual dimorphism, and can be resolved through sex-biased gene expression. A classical theoretical model proposes that unresolved conflicts may persist in the genome and create stable polymorphisms between the sexes at the population level. This model furthermore predicts that the X chromosome should provide a favorable environment for the accumulation of loci under IASC as compared to the autosomes. Although numerous studies have been conducted to test this hypothesis, they provided conflicting results and, so far, no study attempted to map loci under IASC at the genome-wide level. Here, we propose a new methodological framework designed to detect loci under IASC using high-density genetic data. Using this method on HapMap III, a human genome-wide SNP dataset, we identify SNPs showing significant differences in allelic frequencies between the sexes, a signature expected to be observed at loci undergoing IASC. Our results show that the X chromosome contains more signal of IASC than any other chromosome. Moreover, we find that genes showing a signature of IASC are preferentially involved in the determination of traits known to be sexually dimorphic in humans, including external appearance, metabolism and immune system. We also detect genes involved in developmental processes and regulation of gene expression, which is consistent with an ongoing process of IASCs resolution. Furthermore, we find an extreme signal of differentiation between the sexes in a region containing a chromatin insulator binding site, a structure that mediates long-range genomic interactions and therefore affects epigenetic status and gene expression. Our results demonstrate the existence of unresolved IASCs in humans, and suggest their implication in the evolution of human sexual dimorphisms.

SMBE 2014: Genome-wide ancestry patterns in Easter Islanders suggest a pre-European admixture event with Native Americans

Genome-wide ancestry patterns in Easter Islanders suggest a pre-European admixture event with Native Americans

José-Víctor Moreno-Mayar* ¹, Andaine Seguin-Orlando*¹, Morten Rasmussen¹, Erik Thorsby², Simon Rasmussen³, Eske Willerslev¹, Anna-Sapfo Malaspinas^1
1Centre for GeoGenetics. University of Copenhagen, Copenhagen, Denmark, ²Institute of Immunology. Oslo University Hospital. University of Oslo, Oslo, Norway, ³Center for Biological Sequence Analysis. Technical University of Denmark, Kongens Lyngby, Denmark

Easter Island (Rapanui) in Polynesia is one of the most isolated places in the world inhabited by humans. Archaeological and genetic evidence point to a first colonization by Polynesians from the West around 1200 AD. The possibility of an admixture event with Native Americans, before the island was discovered by Europeans in 1722, has been raised due to archaeological and single locus genetic evidence. This evidence, although suggestive of a potential contact, remains inconclusive. In this study we investigate whether such an event happened by generating genome-wide data from Easter Islanders.

We have generated genome-wide data for 10 unrelated reputedly non-admixed Easter Islanders. By using non-parametric multidimensional statistics and clustering methods, we show genome-wide patterns consistent with both Native American and European admixture. We infer local Polynesian, Native American and European ancestry tracts and compare their length distributions to those expected under different demographic history models. We find more support for a model with Native American admixture event that predates a European admixture event. By masking the European and Native American ancestry tracts, we reconstruct the recent history of the Easter Island population compared to other existing genotyped Oceanic populations. These results provide additional detailed insight into the demographic history of Polynesian islanders revealing an outstanding event in recent human history.

SMBE 2014: Whole genome sequencing of an Ashkenazi Jewish reference panel supports population-targeted personal genomics and illuminates Jewish and European origins

Whole genome sequencing of an Ashkenazi Jewish reference panel supports population-targeted personal genomics and illuminates Jewish and European origins

Shai Carmi ¹, Ken Hui², Ethan Kochav¹, Xinmin Liu¹, James Xue¹, Fillan Grady¹, Saurav Guha^{3 ,5}, Kinnari Upadhyay⁶, Danny Ben-Avraham⁶, Semanti Mukherjee^{3 ,4}, B. Monica Bowen², Tinu Thomas⁷, Joseph Vijai⁷, Nir Barzilai⁶, Ariel Darvasi⁸, Kenneth Offit⁷, Susan Bressman⁹, Laurie Ozelius⁵, Inga Peter⁵, Judy Cho², Harry Ostrer⁶, Gil Atzmon⁶, Lorraine Clark¹, Todd Lencz^{3 ,4}, Itsik Pe'er^1
1Columbia University, New York, NY, USA, ²Yale University, New Haven, CT, USA, ³The Feinstein Institute, Manhasset, NY, USA, ⁴The Zucker Hillside Hospital, Glen Oaks, NY, USA, ⁵Icahn School of Medicine at Mount Sinai, New York, NY, USA, ⁶Albert Einstein College of Medicine, New York, NY, USA, ⁷Memorial Sloan Kettering Cancer Center, New York, NY, USA, ⁸The Hebrew University of Jerusalem, Jerusalem, Israel, ⁹Beth Israel Medical Center, New York, NY, USA

The Ashkenazi Jewish (AJ) population is a genetic isolate, close to European and Middle-Eastern populations. AJ experienced a severe medieval bottleneck followed by rapid expansion, leading to genetic diversity patterns conducive to powerful disease mapping. Here, we report the high-depth sequencing of 128 complete genomes of AJ controls. Compared to a European reference panel, our AJ panel is 47% richer in novel variants and 8-fold more effective at filtering benign variants, a necessary step for interpreting AJ clinical genomes. Our panel improves the accuracy of imputation of AJ SNP arrays by 28%, and covers with long, identical-by-descent segments at least one haplotype in ≈67% of the genome of any other AJ individual. Reconstruction of recent AJ history from such segments confirms and quantifies a recent bottleneck of merely ≈350 individuals. Further modeling of ancient histories for AJ and European populations using their joint allele frequency spectrum determines AJ to be an admixture of European (50% of ancestry) and likely Middle-Eastern (50%) origins. This composition facilitates inferring that the split between the two ancestral populations occurred as recently as ≈21 kya, suggesting a predominantly near-Eastern source for the repopulation of Europe at the end of the Last Glacial Maximum.

SMBE 2014: Evidence for different mutation rates across human populations

Evidence for different mutation rates across human populations

Ron Do, David Reich
Department of Genetics, Harvard Medical School, Boston, USA

Although mutation rates (per base pair) have clearly changed across primate evolution, many analyses continue to assume that all present-day human populations have the same mutation rates. Recently, William Amos analyzed 1000 Genomes Project and Complete Genomics sequences and found evidence of significantly higher divergence rates on African than on non-African lineages since separation (W. Amos, PLoS One 4, e63048). The detected pattern was strongest in genomic regions of high polymorphism rate, a pattern that the author hypothesized was due to ‘heterozygote instability’, whereby gene conversion events surrounding heterozygous sites increase the mutation rate. To further test this observation, we measured the relative accumulation of mutations in lineages drawn from two different populations, using 25 deep genome sequences generated according to the same experimental protocol using the Illumina technology. We carried out pairwise comparisons of five sub-Saharan African (Dinka, Mandenka, Mbuti, San, Yoruba) and eight Non-African populations (Australian, Dai, French, Han, Karitiana, Mixe, Papuan, Sardinian) on all divergent sites.  We observed statistically significant differences in the relative accumulation of mutations for many pairs of African and Non-African populations. Among the strongest differences is significantly more lineage-specific mutations in Mbuti than in Han Chinese (R=1.044, standard error (SE) =0.0015).  On average, we observed about 1% more mutations on African lineages compared to Non-African lineages. We also observed some significant differences across non-African populations, with the Han Chinese who have experienced extreme expansions in population size associated with agriculture having more mutations than the Karitiana, a hunter-gatherer population from Amazonia who did not experience such expansions (R=1.015, SE=0.0014).  The results are consistent across both European and African segments of the human reference sequence, so are not an artifact of reference sequence bias. Taken together, these results support the view that per-base pair mutation rates may be dynamically and substantially changing across humans.

Identification of mutation rate polymorphism from genome-wide haplotype data

Cathal Seoighe
National University of Ireland Galway, Galway, Connaught, Ireland

The rate of germline mutation is known to vary significantly between species, but, as yet there are few examples of intra-specific mutation rate polymorphisms. Recent advances in sequencing technologies have enabled direct measurement of the human germline mutation rate for the first time from parent-offspring trios and one large-scale study in the Icelandic population reported that most of the variance in the rate of de novo mutation was the result of paternal age. Here we devise a strategy to infer mutation rate polymorphisms from derived allele profiles and apply this approach to human haplotype data from the one thousand genomes project. We demonstrate using coalescent simulations that a mutation that increases the rate of germline mutation is likely to result in a distinctive pattern of derived alleles in the genomic region in linkage disequilibrium with the affected locus. This signature is characterized by a number of haplotypes with a locally high proportion of derived alleles, against a background in which most of the haplotypes have a typical proportion of derived alleles. We searched for this signature in the one thousand genomes haplotype data and found a striking candidate close to a human histone deacetylase (HDAC2), which has been reported to be involved in the DNA damage response. The signature was found only in haplotypes of African or African-American origin and is consistent with the presence of a low-frequency allele with a significant impact on the germline mutation rate that has persisted for a large number of generations.