Genomewide association of skin color in South Asians

I liked this paper quite a lot. It looked at natural variation in skin color among people from South Asia. (see abstract below)
What they did is looked at 1.6 million SNPs in the individuals in the top 20% of skin darkness versus individuals in the bottom 20% in skin darkness.
Razib has an extensive post on this paper. I'm going to follow the FAQ format that John Hawks sometimes uses (only two questions here, though):

Why this is new and exciting?
According to the authors this is the first genome wide association study on skin pigmentation They focus on subjects who come from a somewhat localized population or set of populations (India, Pakistan, Bangladesh, Sri Lanka), but that have a wide range of skin darkness. One potential caveat is that the subjects live in the UK, thereby minimizing degree of skin darkness, especially given that the researchers use points of measurement that are not all that sun-hidden (forearm and just above the elbow).

So what does it say about the genetics of skin color?
They find the usual suspects (TYR, SLC24A5, and SLC45A2). This can be surprising or unsurprising depending on how you look at it. First it highlights that the effect of SLC24A5 (associated with light skin color in Europeans but not Asians) extends all the way to South Asia. This could be interpreted in several ways. The fact that they find only three genes with strong associations is intriguing, and the fact that SLC24A5 accounts for 30% of skin color variation confirms earlier studies and may highlight once again that skin color may not be controlled by all that many loci... Although, the authors mention that this is likely an underestimate because of reduced power due to the Bonferroni correction.
Lastly, they also state that the "contributions of these polymorphisms to skin pigmentation were found to be independent and additive across genes,"

A Genomewide Association Study of Skin Pigmentation in a South Asian Population

Renee P. Stokowski, P. V. Krishna Pant, Tony Dadd, Amelia Fereday, David A. Hinds, Carl Jarman, Wendy Filsell, Rebecca S. Ginger, Martin R. Green, Frans J. van der Ouderaa, and David R. Cox

The American Journal of Human Genetics, volume 81 (2007), page 000

We have conducted a multistage genomewide association study, using 1,620,742 single-nucleotide polymorphisms to systematically investigate the genetic factors influencing intrinsic skin pigmentation in a population of South Asian descent. Polymorphisms in three genes SLC24A5, TYR, and SLC45A2 yielded highly significant replicated associations with skin-reflectance measurements, an indirect measure of melanin content in the skin. The associations detected in these three genes, in an additive manner, collectively account for a large fraction of the natural variation of skin pigmentation in a South Asian population. Our study is the first to interrogate polymorphisms across the genome, to find genetic determinants of the natural variation of skin pigmentation within a human population.

Neandertals also need their vitamin D

Both Neandertals that they sequenced had a version of MC1R that is not found among modern humans (at least 3,700 of them). This variant is likely to have led to lighter skin/hair. It looks like this will be coming out in Science soon.

A Melanocortin 1 Receptor Allele Suggests Varying Pigmentation Among Neanderthals

Carles Lalueza-Fox, Holger Römpler, David Caramelli, Claudia Stäubert, Giulio Catalano, David Hughes, Nadin Rohland, Elena Pilli, Laura Longo, Silvana Condemi, Marco de la Rasilla, Javier Fortea, Antonio Rosas, Mark Stoneking, Torsten Schöneberg, Jaume Bertranpetit, Michael Hofreiter

The melanocortin 1 receptor (MC1R) regulates pigmentation in humans and other vertebrates. Variants of MC1R with reduced function are associated with pale skin color and red hair in humans primarily of European origin. We amplified and sequenced a fragment of the MC1R gene (mc1r) from two Neanderthal remains. Both specimens have a mutation not found in ~3,700 modern humans. Functional analyses show that this variant reduces MC1R activity to a level that alters hair and/or skin pigmentation in humans. The impaired activity of this variant suggests that Neanderthals varied in pigmentation levels, potentially to the scale observed in modern humans. Our data suggest that inactive MC1R variants evolved independently in both modern humans and Neanderthals.

War promotes altruism and vice-versa

I'll have to take a closer look at how they come up with "conditions likely to have been experienced by late Pleistocene and early Holocene humans" when I have more time... other than that, this seems to make intuitive sense.

The Coevolution of Parochial Altruism and War

Jung-Kyoo Choi and Samuel Bowles

Science 26 October 2007 ; 318:636-640

Abstract: Altruism—benefiting fellow group members at a cost to oneself—and parochialism—hostility toward individuals not of one's own ethnic, racial, or other group—are common human behaviors. The intersection of the two—which we term "parochial altruism"—is puzzling from an evolutionary perspective because altruistic or parochial behavior reduces one's payoffs by comparison to what one would gain by eschewing these behaviors. But parochial altruism could have evolved if parochialism promoted intergroup hostilities and the combination of altruism and parochialism contributed to success in these conflicts. Our game-theoretic analysis and agent-based simulations show that under conditions likely to have been experienced by late Pleistocene and early Holocene humans, neither parochialism nor altruism would have been viable singly, but by promoting group conflict, they could have evolved jointly.

Social Inequality and Health

This was the hook:

Intriguing parallels between civil servant and nonhuman primate hierarchies suggest that highly stratified societies foster health inequalities. Determining how social differences translate into chronic disease remains a challenge, but neuroendocrine pathways appear to play a role.

to a short paper in PLoS Biology that was part of a "Collection on Poverty"
First of all, what happened to Romania, Slovakia and Croatia in their logo below? Is this a prediction of global warming's effect on the Black Sea and the Mediterranean?This paper focused on: how do we explain health inequalities with respect to the stress and changes in endocrine pathways caused by being at the bottom of the social ladder? I'm happy that they referenced Sapolsky and the parallels with other primate hierarchies and measures of cortisol, but I feel that they could have referenced more of the literature on the effect of skin color and racial discrimination on job attainment and health problems, for example. Most of what they talk about in this paper is the inverse gradient between disease related traits and social level. When risk factors are controlled for, (or attempted to control for), they still find that 2/3 of the gradient remains unexplained. Interestingly they find that cancer mortality does not follow that same inverse gradient. Also, interestingly, the risk associated with stress from low status was greater in females.
Since, after controlling for behavioral factors and general obesity they still find much of the gradient unexplained, they transition into their discussion:

That behavior-related factors did not provide a full explanation for the social gradient in metabolic syndrome is consistent with the operation of direct psychosocial and neuroendocrine pathways linking lower social status to CHD risk

...In contrast to this social “embodiment” perspective, it has been argued that biological integrity, in the form of inherited advantage, is the real cause of social inequalities in health.Cognitive function is a high-level expression of this property, and analysis of the changes in test scores over the first ten years of life in a population-based study (the 1970 Birth Cohort) emphasizes the importance of environmental influences. Cognitive performance was first measured at 22 months of age. Children who ranked low at baseline rose through the ranks if their parents were affluent, and conversely, children who ranked high at baseline fell back if their parents were poor. By age seven, the two groups had crossed over in the rankings, whereas children who had both high initial test scores and high social class parents remained near the top of the ranking, and vice versa [8]. These and numerous other findings suggest for the majority of those born without congenital disease, and regardless of the endowment of health capital, a poor early socioeconomic environment is likely to undermine development and later health prospects.

then the author goes on to discuss the lessons to be learned from work by R. Sapolsky on baboons:

This correlation matches the proposition of the late Per Bjorntorp that activity of the hypothalamic-pituitary-adrenal axis links psychosocial factors to metabolic syndrome [11]. Further, Sapolsky provided an example of the physiological effects of hierarchy, free of confounding by smoking and alcohol consumption, both of which influence HDL cholesterol levels.

So can we measure "stress"?

Many questions remain. The quest for a universal stress biomarker, the Holy Grail of “stress biology,” may be a vain enterprise, but with respect to obesity, diabetes, and cardiovascular disease, metabolic syndrome proves to be a useful construct.

I guess they think that metabolic syndrome is a good measure since they find that it is affected only a little by behavioral factors and general obesity.
Finally, props to the author for including info on this study on the effects of football (the real football) results on mortality rates - when you experience stress via your national team's loss in a major tournament:

Box 1. The Power of Mind-Body Interaction: Knockout Stress Triggers Cardiovascular Death among Soccer FansMortality among adults 45 years or over in Holland on 22 June 1996—the day the Dutch football team was eliminated from the European championship—was compared with the 5 days before and after the match and in the same period in 1995 and 1997. Coronary and stroke mortality was increased in men on the day of the match (relative risk 1.51, 95% confidence interval 1.08–2.09). No clear rise in mortality was observed for women (1.11, confidence interval 0.80–1.56). Among men, approximately 14 excess cardiovascular deaths occurred on the day of the match [19].

The paper ends with this juicy outlook into future research possibilities:

More feasibly with the newly available high-throughput genotyping technology, we plan to harness Mendel's second law—nature's randomization—to compare stress hyper-responders with their more even-tempered counterparts. By comparing the lifelong effects of genotype with observed phenotype, we have the potential to break the confounding intrinsic to conventional epidemiology, to clarify what is cause and what is effect.

HapMap II, untaggable SNPs, recombination hotspots and the future

so like I said in the previous post, 2 million additional SNPs were typed in the four HapMap populations, and the findings were reported in the latest Nature issue.
In that paper, they go over some of the patterns they find regarding, untaggable SNPs, recombination hotspots, and discuss some of the related ongoing and future genotyping efforts.
One of their main findings is the relatively high proportion of SNPs that are untaggable (in regions of high recombination, for example):

Despite the SNP density of the Phase II HapMap, there are high-frequency SNPs for which no tag can be identified. Among high-frequency SNPs (MAF 0.2), we marked as untaggable SNPs to which no other SNP within 100 kb has an r² value of at least 0.2. In Phase II, approximately 0.5–1.0% of all high-frequency SNPs are untaggable and the proportion in YRI is approximately twice as high as in the other panels.

so are these SNPs untaggable due to high local recombination rates?: (answer: yes, probably)

Over 50% of all untaggable SNPs lie within 1 kb of the centre of a detected recombination hotspot and over 90% are within 5 kb. Because only 3–4% of all SNPs lie within 1 kb from the centre of a detected recombination hotspot (16% are within 5 kb), this constitutes a marked enrichment and implies that at least 10% of all SNPs within 1 kb of hotspots are untaggable. The implication for association mapping is that when a region of interest contains a known hotspot it may be prudent to perform additional sequencing within the hotspot. Many of the variants identified in this manner will be untaggable SNPs that should be genotyped directly in association studies.

They also discuss something that I've always wondered about. What determines where recombination takes place? According to them, some of the leading ideas are specific DNA motifs that influence hotspot location and some other things about the sequence including locations of genes - so, in other words, it seems that no one really knows for sure.
According to the authors:

The Phase II HapMap provides the resolution to separate these influences

What they find:

Within the transcribed region of genes there is a marked decrease in the estimated recombination rate. However, 5' of the transcription start site is a peak in recombination rate with a corresponding local increase in the density of hotspot motifs. This region also shows a marked increase in G+C content, reflecting the presence of CpG islands in promoter regions. There is also an asymmetry in recombination rate across genes, with recombination rates 3' of transcribed regions being elevated (as are motif density and G+C content) compared to regions 5' of genes. Studies in yeast have previously suggested an association between promoter regions and recombination hotspots³⁹. Our results suggest a significant, although weak, relationship between promoters and recombination in humans. Nevertheless, the vast majority of hotspots in the human genome are not in gene promoters. The association may reflect a general association between regions of accessible chromatin and crossover activity.

They then examine if recombination happens more around some types of genes. They use the Panther database of gene ontology to classify the genes and see if there are any noticeable patterns, and they find some interesting ones:

Average recombination rates vary more than sixfold among such gene classes (Fig. 5b), with defence and immunity genes showing the highest rates (1.9 cM Mb-1) and chaperones showing the lowest rates (0.3 cM Mb-1). Gene functions associated with cell surfaces and external functions tend to show higher recombination rates (immunity, cell adhesion, extracellular matrix, ion channels, signalling) whereas those with lower recombination rates are typically internal to cells (chaperones, ligase, isomerase, synthase). Controlling for systematic differences between gene classes in base composition and gene clustering, the differences between groups remain significant. We also find that the density of hotspot-associated DNA motifs varies systematically among gene classes and that variation in motif density explains over 50% of the variance in recombination rate among gene functions.

and then they briefly discuss the interesting evolutionary implications: namely that highly conserved gene functions are "protected" from recombination, while those involved in defnese and immunity from the everchanging outside world are more likely to be shuffled around...makes sense, I suppose.

...hotspots may be selected against in some highly conserved parts of the genome. In regions exposed to recurrent selection (for example, from changes in environment or pathogen pressure) it is plausible that recombination may be selected for. However, because the fine-scale structure of recombination seems to evolve rapidly, it will be important to learn whether patterns of recombination rate heterogeneity among molecular functions are conserved between species.

They go on to discuss some of the ongoing related projects: basically more populations, and more forms of variation:

NHGRI collection has cell lines for the following populations that they are currently hoping to get HapMap-style SNP genotypes on: (some of the populations are interesting and the website has interesting descriptions of them, such as the Gujarati Indians in Houston)

Maasai in Kinyawa, Kenya
Yoruba in Ibadan, Nigeria
Han Chinese in Beijing, China
Japanese in Tokyo, Japan
Luhya in Webuye, Kenya
Chinese in Metropolitan Denver, CO, USA
Gujarati Indians in Houston, TX, USA
Toscani in Italia
Mexican Ancestry in Los Angeles, CA, USA
African Ancestry in SW USA

Why don't they do this with the CEPH panel instead?
There are also people looking at CNVs on the original HapMap samples,... and then at some point, whole genome sequencing on these samples.
At some point I'll get to the selection paper.

John Hawks on the FoxP2 in Neandertals

John Hawks came up with a FAQ on the recent finding that Neandertals (or at least the two they got DNA from) had the same version of FoxP2 as us.
He raises some interesting points. First is this the best strategy vis-a-vis getting the most info out of a precious DNA resource. What other genes would be interesting to look at?
The FAQ goes on to questions about what we know about the role of FoxP2 in language, what we know about whether Neanderthals were capable of speech.
Then..., I like this question:

We all know that the Neandertal genome is riddled with contamination from modern humans. Isn't the null hypothesis that we have a modern human sequence here because it is a modern human?

According to John, we shouldn't worry too much:

For this study, Krause et al. (2007) developed a test of nuclear DNA contamination: they identified seven gene variants that differ between the recovered Vindija Vi 33.16 nuclear genome and all known living humans. In other words, these are human-derived mutations that are absent from the only known Neandertal nuclear genome. Then, they probed the El Sidrón bones for these sites. They found only the ancestral form in their extracts of both bones -- presumably because no human contaminants were present in their samples.

he then goes on to discuss vasious timing issues. I started getting lost at this point. He does this in the context of the possibility of this being an example of introgression: i.e. the Neandertals got this version of FoxP2 via mating with humans. I guess you could picture a really talkative "modern human" female mating with a grunting Neandertal male. Or it could be a case of introgression the other way around (Neadertals into moderns):

So, considering that the El Sidrón samples both share the human-derived amino acid substitutions on the same haplotype as modern humans, complete with all the high-frequency derived SNPs, it seems almost certain that the gene introgressed into Neandertals from modern humans.

Or, there's one other option. One of the El Sidrón bones includes a relatively rare (in humans) ancestral SNP allele at one of those linked sites where the derived allele is at very high frequency in humans. One explanation: the selected mutation arose in Neandertals and introgressed into other humans. That would explain why this Neandertal didn't have a SNP variant on its FoxP2 haplotype that later became very common in humans: Neandertals had the new FoxP2 first.

I had a hard time following the reasoning throughout his post (mainly due to my unfamiliarity with all the intricacies, and due to time limitations), but thanks, John, for breaking it down so thoroughly for us.

HapMap part deux

There's a lot of stuff going on right now, but I thought this was the most important. The HapMap project came out with their genotypes for another 2 million SNPs (so now they're up to 3 million SNPs) in their four populations (really three, it could be argued). In the latest Nature they lay out all their findings, including the ones about tests of positive selection.
In a report called "So similar, yet so different" by Erika Check Hayden, she discusses how we're finding a lot more genetic diversity between humans than previously thought:

• Venter diploid genome
• CNVs
• SNPs in this HapMap go-round

here's a snippet about those SNPs:

... in the updated HapMap, 1% of the more than 3 million SNPs that have now been analysed cannot be grouped with their neighbours to mark identical chunks of DNA. These 'untaggable SNPs' reveal parts of the genome that vary greatly between people. “These untaggable SNPs are completely doing their own thing,” McVean says. “It's not a high percentage of SNPs, but it's still a lot of them.”

...then, this great snippet. The second paragraph is pretty interesting, and very related to the research that I've been doing.

Scientists are now obtaining DNA from seven more populations with African, Asian and European ancestry that could help explain the origin of the mystery SNPs. They are also discussing a massive new bout of sequencing in an international project involving Chinese, British and US funders that would use new technologies to sequence the genomes of 1,000 individuals. Along with the two individual genome sequences already released4, these data will fuel a field that is set to explode over the next year: the hunt for genetic signatures that discriminate between smaller and smaller groups.

“The HapMap data can clearly tell you whether you are African or Chinese, but the question becomes, how far can you take that?” asks population geneticist Carlos Bustamante from Cornell University in Ithaca, New York. “Can you predict whether somebody comes from one village or another? We are going to see all kinds of stuff we would never have imagined was possible.”

I'll say what I can about the positive selection paper part of all this in a future post.

Sun exposure, vitamin D, and breast cancer

Here's a study looking at the relationship between amount of sun exposure and breast cancer in a diverse sample of Whites, Hispanics, and African Americans Lighter skinned people who have a lot of sun exposure have lower rates of breast cancer. They did not find any "protective" effect of sun exposure on breast cancer among women with darker constitutive skin pigmentation: their short explanation:

"It is possible that, in more heavily pigmented persons, the sun exposure index usedin this study is a less sensitive measure of past sun exposure and/or that, in these women, such exposure generated less vitamin D (51)."

51. Harris SS. Vitamin D and African Americans. J Nutr (2006) 136:1126–9

They also looked at whether there were any associations with three polymorphisms in the Vitamin D receptor gene, but didn't find any.

Sun Exposure, Vitamin D Receptor Gene Polymorphisms, and Breast Cancer Risk in a Multiethnic Population.

John EM, Schwartz GG, Koo J, Wang W, Ingles SA.Northern California Cancer Center, Fremont, CA.

Am J Epidemiol. 2007 Oct 12; [Epub ahead of print]

Considerable evidence indicates that vitamin D may reduce the risk of several cancers, including breast cancer. This study examined associations of breast cancer with sun exposure, the principal source of vitamin D, and vitamin D receptor gene (VDR) polymorphisms (FokI, TaqI, BglI) in a population-based case-control study of Hispanic, African-American, and non-Hispanic White women aged 35-79 years from the San Francisco Bay Area of California (1995-2003). In-person interviews were obtained for 1,788 newly diagnosed cases and 2,129 controls. Skin pigmentation measurements were taken on the upper underarm (a sun-protected site that measures constitutive pigmentation) and on the forehead (a sun-exposed site) using reflectometry. Biospecimens were collected for a subset of the study population (814 cases, 910 controls). A high sun exposure index based on reflectometry was associated with reduced risk of advanced breast cancer among women with light constitutive skin pigmentation (odds ratio = 0.53, 95% confidence interval: 0.31, 0.91). The association did not vary with VDR genotype. No associations were found for women with medium or dark pigmentation. Localized breast cancer was not associated with sun exposure or VDR genotype. This study supports the hypothesis that sunlight exposure reduces risk of advanced breast cancer among women with light skin pigmentation.

Primate bipedalism: who, when, why

For those of you interested in primate bipedality, there's a paper out in PLoS One titled:
Homeotic Evolution in the Mammalia: Diversification of Therian Axial Seriation and the Morphogenetic Basis of Human Origins
by Aaron G. Filler
The paper is pretty complex, and I didn't bother trudging through all the analyses of spine organization, but the news summary of the paper is a convenient shortcut to understanding the possible implications:

"This research pushes back the date for the origins of bipedalism roughly 15 million years, to before the last common ancestor of humans, chimps, gorillas and orangutans, as well as lesser apes such as gibbons. The results match up with recent findings that suggest upright walking might have started before humanity's ancestors even left the trees."

Baboons, social intelligence, and large brain size

Since I have some background in human evolutionary ecology, I am interested in why humans have such big brains. There are several hypotheses out there for what ecological factors drive large brain size, some of which I've discussed on this blog.
In an article by Nick Wade in the NYT about the social smarts of baboons, he and Dr. Seyfarth give their opinion:

It is far from clear why humans acquired a strong theory of mind faculty and baboons did not. Another difference between the two species is brain size. Some biologists have suggested that the demands of social living were the evolutionary pressure that enhanced the size of the brain. But the largest brains occur in chimpanzees and humans, who live in smaller groups than baboons.

But both chimps and humans use tools. Possibly social life drove the evolution of the primate brain to a certain point, and the stimulus of tool use then took over. Use of tools would have spurred communication, as the owner of a tool explained to others how to use it. But that requires a theory of mind, and Dr. Cheney and Dr. Seyfarth are skeptical of claims that chimpanzees have a theory of mind, in part because the experiments supporting that position have been conducted on captive chimps. “It’s bewildering to us that none of the people who study ape cognition have been motivated to study wild chimpanzees,” Dr. Cheney said.

“Baboons provide you with an example of what sort of social and cognitive complexity is possible in the absence of language and a theory of mind,” she said. “The selective forces that gave rise to our large brains and our full-blown theory of mind remain mysterious, at least to us.”

Eye on DNA

If you're interested in all things DNA, I recommend you take a look at the Eye on DNA blog. Some of the posts in the past week have been pretty interesting.

Inactivation of the human version of genes involved in olfaction and skin

Inactivation of MOXD2 and S100A15A by Exon Deletion during Human Evolution

Yoonsoo Hahn, Sangkyun Jeong, Byungkook Lee

Molecular Biology and Evolution 2007 24(10):2203-2212

Abstract: We devised a bioinformatics method for systematic identification of putative human-specific exon-deletion mutations that occurred after the divergence of human and chimpanzee and experimentally verified 2 of the predicted mutations in MOXD2 and S100A15A genes. MOXD2 gene encodes a monooxygenase that is highly conserved in mammals and is mostly expressed in the olfactory epithelium in mouse. The presence of a deletion of the last 2 exons and a polymorphic nonsense mutation in exon 6 suggests that MOXD2 gene is inactive in humans. S100A15A is a member of the S100 family of calcium-binding proteins, the mouse ortholog of which is expressed during epidermal maturation. Human S100A15A gene is likely to be inactive because the start codon–bearing exon is deleted in human. We propose that modification or inactivation of MOXD2 and S100A15A genes have contributed to the loss of certain smell sense in humans and to the development of human skin.

Genetic vs. Language diversity

This one looks good. The main thing here is that they do their analysis of genetic diversity vs. geographic/language diversity at a very fine scale. They find a strong relationship between language (as measured by cognates: words with a common origin) and genetics (Y chromosome lineages). They do this on Sumba, the island in the south central area of Indonesia, just south of Flores

Coevolution of languages and genes on the island of Sumba, eastern Indonesia

J. Stephen Lansing, Murray P. Cox, Sean S. Downey, Brandon M. Gabler, Brian Hallmark, Tatiana M. Karafet, Peter Norquest , John W. Schoenfelder , Herawati Sudoyo , Joseph C. Watkins, and Michael F. Hammer

PNAS Published online before print October 3, 2007

Abstract: Numerous studies indicate strong associations between languages and genes among human populations at the global scale, but all broader scale genetic and linguistic patterns must arise from processes originating at the community level. We examine linguistic and genetic variation in a contact zone on the eastern Indonesian island of Sumba, where Neolithic Austronesian farming communities settled and began interacting with aboriginal foraging societies 3,500 years ago. Phylogenetic reconstruction based on a 200-word Swadesh list sampled from 29 localities supports the hypothesis that Sumbanese languages derive from a single ancestral Austronesian language. However, the proportion of cognates (words with a common origin) traceable to Proto-Austronesian (PAn) varies among language subgroups distributed across the island. Interestingly, a positive correlation was found between the percentage of Y chromosome lineages that derive from Austronesian (as opposed to aboriginal) ancestors and the retention of PAn cognates. We also find a striking correlation between the percentage of PAn cognates and geographic distance from the site where many Sumbanese believe their ancestors arrived on the island. These language–gene–geography correlations, unprecedented at such a fine scale, imply that historical patterns of social interaction between expanding farmers and resident hunter-gatherers largely explain community-level language evolution on Sumba. We propose a model to explain linguistic and demographic coevolution at fine spatial and temporal scales.

Annual Review of Anthropology

There's a few interesting reviews in this issue (and they're open access):

Evolutionary Medicine

Wenda R. Trevathan

Biological anthropologists have been contributing to what is now referred to as evolutionary medicine for more than a half century, although the phrase itself began to be widely used only in the early 1990s. Three topics in which anthropological contributions have been especially significant include nutrition, reproductive health, and chronic disease. A major focus in nutrition and reproduction is the health consequences of evolved biology in the context of contemporary diets, lifestyles, and contraceptive practices seen in industrialized nations. Contributions from anthropology include efforts to assess and redefine the concept of “normal” in health indicators, emphasis on developmental processes in addition to proximate and ultimate forces affecting health, and enhancement of understanding of contemporary health disparities. Evolutionary medicine is a highly interdisciplinary field, and anthropologists have played important roles in directing attention not only to evolutionary processes but also to sociocultural and sociopolitical effects on human health.

Genomic Comparisons of Humans and Chimpanzees

Ajit Varki and ­David L. Nelson

The genome consists of the entire DNA present in the nucleus of the fertilized embryo, which is then duplicated in every cell in the body. A draft sequence of the chimpanzee genome is now available, providing opportunities to better understand genetic contributions to human evolution, development, and disease. Sequence differences from the human genome were confirmed to be 1% in areas that can be precisely aligned, representing 35 million single base-pair differences. Some 45 million nucleotides of insertions and deletions unique to each lineage were also discovered, making the actual difference between the two genomes 4%. We discuss the opportunities and challenges that arise from this information and the need for comparison with additional species, as well as population genetic studies. Finally, we present a few examples of interesting findings resulting from genome-wide analyses, candidate gene studies, and combined approaches, emphasizing the pros and cons of each approach.

Genetic Basis of Physical Fitness

Hugh Montgomery and ­Latif Safari

Environmental stimuli interact with common genetic variants to determine individual characteristics including physical performance: 80% of variation in arm eccentric flexor strength and grip strength may be genetically determined. However, many physical characteristics and physiological processes determine physical performance, and each is regulated by a large number of genes: strong genetic influences on maximum exertional oxygen uptake, heart size, lean mass, skeletal muscle growth, and bone mineral density have all been described. To date few variants strongly influencing global performance have been identified. One such is the presence (Insertion, I allele) rather than absence (Deletion, D allele) of a DNA segment in the gene encoding angiotensin-converting enzyme (ACE): The I allele has been associated with fatigue resistance/endurance, and the D-allele with strength gain.

The Genetic Reinscription of Race
Nadia Abu El-Haj

Critics have debated for the past decade or more whether race is dead or alive in “the new genetics”: Is genomics opening up novel terrains for social identities or is it reauthorizing race? I explore the relationship between race and the new genetics by considering whether this “race” is the same scientific object as that produced by race science and whether these race-making practices are animated by similar social and political logics. I consider the styles of reasoning characteristic of the scientific work together with the economic and political rationalities of neo-liberalism, including identity politics as it meets biological citizenship. I seek to understand why and how group-based diversity emerges as an object of value—something to be studied and specified, something to be fought for and embraced, and something that is profitable—in the networks that sustain the world of (post)genomics today.

Signature of selection in genes that underlie schizophrenia

I've always been intrigued by this hypothesis for disorders such as schizophrenia, autism, and William's syndrome: "genetic liability to schizophrenia has evolved as a secondary consequence of selection for human cognitive traits" or "maladaptive by-product of adaptive changes during human evolution"
... but I'm not sure yet how to interpret the significance of what they've found here.

Adaptive evolution of genes underlying schizophrenia

Bernard Crespi, Kyle Summers, Steve Dorus

Proc. Roy. Soc. B. Volume 274, Number 1627 / November 22, 2007

Abstract: Schizophrenia poses an evolutionary-genetic paradox because it exhibits strongly negative fitness effects and high heritability, yet it persists at a prevalence of approximately 1% across all human cultures. Recent theory has proposed a resolution: that genetic liability to schizophrenia has evolved as a secondary consequence of selection for human cognitive traits. This hypothesis predicts that genes increasing the risk of this disorder have been subject to positive selection in the evolutionary history of humans and other primates. We evaluated this prediction using tests for recent selective sweeps in human populations and maximum-likelihood tests for selection during primate evolution. Significant evidence for positive selection was evident using one or both methods for 28 of 76 genes demonstrated to mediate liability to schizophrenia, including DISC1, DTNBP1 and NRG1, which exhibit especially strong and well-replicated functional and genetic links to this disorder. Strong evidence of non-neutral, accelerated evolution was found for DISC1, particularly for exon 2, the only coding region within the schizophrenia-associated haplotype. Additionally, genes associated with schizophrenia exhibited a statistically significant enrichment in their signals of positive selection in HapMap and PAML analyses of evolution along the human lineage, when compared with a control set of genes involved in neuronal activities. The selective forces underlying adaptive evolution of these genes remain largely unknown, but these findings provide convergent evidence consistent with the hypothesis that schizophrenia represents, in part, a maladaptive by-product of adaptive changes during human evolution.

Dog genetics

Science has a story about the use of domestic dog breeds to understand the genetic basis for various behavioral, morphological, and disease related traits.

The Geneticist's Best Friend
Elizabeth Pennisi
Science 21 September 2007: Vol. 317. no. 5845, pp. 1668 - 1671

Many dog breeds are like large inbred families, and many times have known genealogies, so that each breed is, as Elaine Ostrander describes it, "like a mini Iceland or Finland". Along with Carlos Bustamante, they are developing the dog equivalent of HapMap: CANMAP (didn't see it online yet)

By the way, Science has several other papers on dog genetics:
Genetic Evidence for an East Asian Origin of Domestic Dogs
Genetic Structure of the Purebred Domestic Dog
A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs
and cognition:
Man's Best Friend(s) Reveal the Possible Roots of Social Intelligence

I think there is a lot of potential here... it sounds like European scientists are leading the effort. One of my favorite examples is the foxes in Russia who were bred to be docile and at the same time developed a lighter coat. I'm not sure exactly what's going on there but it seems to be uncovering some kind of pleiotropy: the genetics of behavior somehow linked to the genetics of coat color.