Anthropology.net

Last week at the Royal Society in London, research was presented suggesting that Neandertals not only interbred with H. sapiens sapiens, but that their genes were helpful to modern people moving out of Africa.

This pioneering study was led by Peter Parham of Stanford University, and was only possible after the draft genome of H. neanderthalensis was published. The researchers looked at human leukocyte antigens (HLAs), genes important to the functioning of the immune system.

Different regions of the world are known to have unique HLAs, because different variations create specific disease resistances. It would have been advantageous for the earliest modern humans to breed with a species (or subspecies) already adapted to living in a different climate. Moderns could have picked up helpful genes that were already in existence from Neandertal populations, which would have possibly allowed their populations to expand more rapidly. Why wait for random mutation when you can interbreed with a people already successfully adapted to an area?

Neandertal Child Reconstruction

While only approximately 6% of the modern European genome was contributed from earlier hominins, around half of specific HLAs can be attributed to these earlier forms of people. As a form of further substantiation, Europeans have HLA variations present within the Neandertal genome not found in Africans. Interestingly, Asian populations today also have a variation not present anywhere else, which could indicate Denisovan (mystery Siberian hominin) admixture.

As if the draft sequence showing interbreeding was not enough last year– this study has raised the bar on the type of information we can hope to glean from looking at ancient DNA. There was a time when archaeology and anatomy were the only windows we had into our ancestral relatives. It will be exciting to see what is uncovered next.

By Matthew Magnani

Both Razib and Dienekes have put a posts about this new Current Biology paper, “Correlation between Genetic and Geographic Structure in Europe.” The authors of the paper compare the genetic make up of 2,514 individuals from Europe using the Affymetrix GeneChip Human Mapping 500K Array Set.

Correlation between Genetic and Geographic Structure in Europe

Always the over achiever of science blogging, Razib has dutifully labeled the populations on the graph. His modifications help better visualize the genetic similarities and differences among and between the European populations tested. And there are some interesting patterns. There’s a similarity among northern European populations as well as a similarity among southern European populations.

Fins tested are the least similar group to other European populations. Swedes and Spanish people are clearly different, while the Irish and British share a lot of admixture among the 500,000 SNPs tested. So what does that all mean? This result indicates that there is a genetic component to European ethnic groups.

Not entirely surprising, because in 2006, we saw the open access journal PLoS Genetics publish a typing of 5,000 SNPs among about 1,000 Europeans and European Americans. In that paper, the researchers were able to resolve the genetic differences between northern and southern European groups. Image below. Also, in January of this year I read and reviewed two papers that did similar tests, comparing 300,000 SNPs between approximately 4,198 European Americans. After some principal component analyses (PCA), there was a clear distinction between individuals with northern from southern European ancestry, as well as separation of Italian, Spanish, and Greek individuals from those of Ashkenazi Jewish ancestry.

European Population Substructure

PLoS Genetics has also recently published a similar paper, “Tracing Sub-Structure in the European American Population with PCA-Informative Marker,” which announces a purely computational method of identifying ancestry — one that doesn’t require a poll of the individuals’ identified ethnic background. The researchers analyzed 1,521 individuals for more than 300,000 SNPs across the entire genome.

While not as robust of a data set as the Current Biology paper, the authors were able to pluck out 200 ancestry informative SNPs that accurately predict fine structures in European American datasets, as identified by PCA. They did so by removing any redundant SNPs uncovered during the modeling process. Moreover, much of the genetic variation identified were between the northern and southern European ancestry groups.

Going back to the ‘is this surprising?’ point, in 1990, Barbujani et al. noted the delineation of northern and southern Europeans between the distribution of 63 allele frequences, in “Zones of sharp genetic change in Europe are also linguistic boundaries,” and attributed the language affiliation of European populations playing a major role in maintaining and probably causing genetic differences. Makes sense.

LAO, O., LU, T., NOTHNAGEL, M., JUNGE, O., FREITAGWOLF, S., CALIEBE, A., BALASCAKOVA, M., BERTRANPETIT, J., BINDOFF, L., COMAS, D. (2008). Correlation between Genetic and Geographic Structure in Europe. Current Biology DOI: 10.1016/j.cub.2008.07.049

Paschou, P., Drineas, P., Lewis, J., Nievergelt, C.M., Nickerson, D.A., Smith, J.D., Ridker, P.M., Chasman, D.I., Krauss, R.M., Ziv, E., Pritchard, J.K. (2008). Tracing Sub-Structure in the European American Population with PCA-Informative Markers. PLoS Genetics, 4(7), e1000114. DOI: 10.1371/journal.pgen.1000114

Two similar papers published the latest issues of Nature and Genome Research do high-resolution analyses of the structure of the human genome. They differ in methodology, but have some cool conclusions. The Nature paper, “Mapping and sequencing of structural variation from eight human genomes,” created libraries of 4 African, 2 Asian, and 2 European genomes. From these libraries they created thousands of clones to figure out if there are structural variations in genomes of these eight individuals from diverse geographic ancestry.

The Genome Research paper, “Scanning the human genome at kilobase resolution,” used ditag genome scanning (DGS) to analyze the human genome in high resolution. This method is really similar to serial analysis of gene expression (SAGE), in that genome is fragmented, each tag is ligated with a marker, and a sequencing technique (454 in this particular study) is used ultimately to determine the origin of the fragment in genome. The authors of this paper report that their method was strong enough to provides a kilobase resolution for studying genome structure. DGS is also highly specific and can cover a lot of the genome. Downstream applications of DGS are to validate assembled genomes but also to compare genome similarity and variation in normal populations.

Both methods are able to identify genomic abnormalities like insertions, inversions, deletions, and translocations, much better than current technologies. But why is this all important to anthropology? The Nature paper shows how they were able to find 525 new insertion sequences that are not present in the human reference genome. These new insertion sequences are shown to be variable in copy number between individuals, which ultimately make for 525 new ancestry inherited markers. Furthermore, when the authors of the Nature paper sequenced their clones they were able to find an additional 261 structural variants which reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome.

One last point, most ancestry inherited markers have been SNPs, but more recent research on the human genome has shown, however, that larger-scale differences like the copy number variations (CNVs) and others screened in these two papers, may account for a great deal of genetic variation among individuals.

Got race?

Kidd, J.M., Cooper, G.M., Donahue, W.F., Hayden, H.S., Sampas, N., Graves, T., Hansen, N., Teague, B., Alkan, C., Antonacci, F., Haugen, E., Zerr, T., Yamada, N.A., Tsang, P., Newman, T.L., Tüzün, E., Cheng, Z., Ebling, H.M., Tusneem, N., David, R., Gillett, W., Phelps, K.A., Weaver, M., Saranga, D., Brand, A., Tao, W., Gustafson, E., McKernan, K., Chen, L., Malig, M., Smith, J.D., Korn, J.M., McCarroll, S.A., Altshuler, D.A., Peiffer, D.A., Dorschner, M., Stamatoyannopoulos, J., Schwartz, D., Nickerson, D.A., Mullikin, J.C., Wilson, R.K., Bruhn, L., Olson, M.V., Kaul, R., Smith, D.R., Eichler, E.E. (2008). Mapping and sequencing of structural variation from eight human genomes. Nature, 453(7191), 56-64. DOI: 10.1038/nature06862

Chen, J., Kim, Y.C., Jung, Y., Xuan, Z., Dworkin, G., Zhang, Y., Zhang, M.Q., Wang, S.M. (2008). Scanning the human genome at kilobase resolution. Genome Research DOI: 10.1101/gr.068304.107

I welcome the news of the 1,000 human genome project that was announced a couple days ago eagerly.  It is a really ambitious effort that will involve sequencing (parts of) the genomes of at least a thousand people from around the world to create the most detailed and useful picture to date of human genetic variation.

As sweep of Gene Expression points out, the project won’t be actually sequencing the genomes of 1,000 people. Rather, six individuals from two families, will get their entire genomes sequenced. 180 different people, from European, Chinese, Japanese, and Nigerian populations will get a more shallow sequence. And then the rest will be sequenced in all of the known protein-coding regions from 1000-2000 genes in over 1000 people. Here are the populations that will be sampled,

“Yoruba in Ibadan, Nigeria; Japanese in Tokyo; Chinese in Beijing; Utah residents with ancestry from northern and western Europe; Luhya in Webuye, Kenya; Maasai in Kinyawa, Kenya; Toscani in Italy; Gujarati Indians in Houston; Chinese in metropolitan Denver; people of Mexican ancestry in Los Angeles; and people of African ancestry in the southwestern United States. “

Much of the press is misinforming people, saying the actually genomes of 1,000 people will be sequenced. That’s a monumental and costly effort, even with the advances we have in sequencing technology. But the data will be invaluable because it will provide a lot of resolution in genetic variation from over 1,000 people. I can’t wait to see what they figure out in three years time. In the mean time, I guess book marking the project’s page, 1000genomes.org, and checking in once in a while to see the progress wouldn’t be a bad idea!

The breakthrough of 2007, as announced by AAAS, the nonprofit organization that publishes Science, is human genetic variation. Human genetic variation has been studied for quite sometime and the primary reason to study genetic variation in humans is to discover and describe the linkage of genes to many human diseases. This is an increasingly powerful motivation in light of our growing understanding of the contribution that genes make to the development of diseases such as cancer, heart disease, etc.

In 2007, we saw many publications in very prestigious journals that used genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease, and I think that’s where the AAAS felt motivated to call human genetic variation the breakthrough of the year. May of 2007, Nature ran a paper where the sample size was around 17,000 and in June, Science published a paper with around 13,00 samples!

But the limelight’s not all in medicine. The impact of human genetic variation in anthropology is just as fascinating. For the last 30 or so years, we have gotten a glimpse of what genetic variation has to offer in helping anthropology; and I hope we can all appreciate (ahem, Martin) that we have another tool in our belt to help us understand human migrations and population structures. With some of the first theoretical papers coming out in ’70′s, I’ve appreciated how fast the field has progressed and how much resolution we now have to understand migratory patterns and the genetic composition of ethnic groups.

For example, in the late ’90′s, we read how Y chromosome sequences tend to be more localized geographically than those of mtDNA. This is an important study for anthropology. Why? The difference seen between female and male migration rates, tells us of human behaviors… women move away from their homes and into the male mate’s natal household far more often than the reverse scenario. Genetic data like this documents us many human populations practiced patrilocal residence, which is a term anyone well versed in socio-cultural anthropology would know by heart. There are a few populations that operate(d) with an opposite social system, such as the Chaco Canyon people, the Nair in Kerala, India, and the Mosou in southern China. But these populations aren’t the norm. For the most part human populations have been paternal and this genetic data supplements the ethnographic, archaeological, and historical data.

In 2007, several human genetic studies told us of how the Americas were peopled. One study analyzed single nucleotide polymorphisms (SNPs) from around 46 different populations within the Americas and Asia to tell us that people camped out in Beringia for a while before making it down to North America and then South America. SNPs are a form of genetic variation, in that a SNP is the difference of one base pair in the same location between two or more alleles.

In late 2007, we also saw a boom in personal genome products from the corporate sector. These products, such as kits from 23andMe, deCODEme, Family Tree DNA, dna.ancestry.com, etc. screen for SNPs to tell us our propensity for some heritable diseases but also our ethnic background. If you’re curious, Mark Fletcher of Wingedpig discussed his results from 23andMe, Myles Axton of Nature Genetics shared his deCODEme results at Free Association, and Megan Smolenyak put up a 17 minute screencast discussion of her husband’s deCODEme results.

Not everyone trusts these sorts of studies. For example, Meredith Small said DNA testing is a scam… and like Martin, argues that our genetic composition/variation can not ultimately tell us who we are. They say that personal identity is not found between base pairs of long sequences. Rather, identityis more effectively found in who humans have associated with, what culture(s) humans followed and are following, what humans do in their daily lives. As an someone trained in archaeology, I can see why Martin sees it this way. He even says his primary expertise is in studying material cultural, a product of human society and culture. As a cultural anthropologist, I can also see why Meredith Small is touting up the we are people… social beings. With their foundations in the social and cultural aspect of anthropology I’m not surprised that they are defending identity and ethnicity as social.

But ethnicity is not entirely social, there definitely is a biological component to ethnicity. The biological component of ethnicity can be seen in the similar phenotype of an ethnic group. Without being too offensive, I think we can all agree that the shape of the eyes of people from China or Japan have a characteristic shape that differ from other ethnicities. Furthermore, for anyone with a background in forensic anthropology, shovel shaped incisors indicate native American decent. Honing in on the genetic aspect of race, in 1997, a Nature paper demonstrated that around ~40% of Jewish males who shared an oral tradition of being Cohanim, also shared a unique set of SNP called the Cohen Modal Haplotype which is on the Y chromosome. Tracing this haplotype, we see it is also present in Italian, Lemba, and Kurdish populations which tells us of integration patterns.

There’s plenty of other haplotypes and genetic markers that help identify backgrounds. Large projects such as the HapMap and National Geographic Genographic projects are collecting data and resolving more haplotypes and genetic markers that can be used in a wide variety of applications. In one situation that comes to my mind, we saw how the unique mtDNA composition of a man named Yu Hong matched the normal composition of Europeans. This genetic evidence correlated with the archaeological evidence helped fulfill our understanding of Yu Hong’s identity.

Ultimately, humans can be classified into groups based on our biological traits, both phenotypically and genetically. Just like we can classify groups based on their cultural traits, such as the style of an artifact, the linguistic similarities. It is not wrong to classify people into groups. It is wrong how people interpret these classifications and apply them, and it is just as wrong for people to shun away any discussion of classifying people!

So, I am surprised that Martin said ethnic essentialism is a thing of the past. It is not a thing of the past. Despite the reductionism shown by the American Anthropological Association’s understanding race project, discussions of ethnic essentialism are a very active and modern aspect within anthropology. Recently, we had our own lively and very informative discussion on race. I hope it to always be an active discussion too. I hope it never stops because it is a very important part of practicing science… to be inquisitive and open. We should always be questioning and investigating. And just because there was a popular movement to eradicate the concept of race decades ago, I don’t think we should dust off our hands and call the debate resolved. I hope that he will once recognize his comment reflects a level of ignorance; in their own way Martin and Small are effectively bullying away any re-evaluation of the biological basis for race because they live by the mantra that “it is an outdated way of thinking.”

Hat tip to Razib.

The web is abuzz over a new publication in PLoS Genetics about a single main migration across Bering Strait. From what I can tell, this new paper, “Genetic Variation and Population Structure,” coincides with a recent publication in PLoS One that sampled mtDNA and figured out people moved in waves, but first they spent some time in Beringia.

Both of these papers use microsattelites or SNPs in genes from native American populations to answer the question, did a small population from Siberia trek across the Bering Strait land bridge some 12,000 years ago and give rise to the native peoples of North and South America? Or did people come from other parts of Asia or Polynesia, arriving in multiple times, at several places on the two continents, by sea as well as by land, in successive migrations that began as early as 30,000 years ago?

To answer this question, the authors picked out 678 markers in the DNA of present-day members of 29 Native American populations across North, Central and South America. They also analyzed data from two Siberian groups. The figure to your right is from the publication, which illustrates who and where the populations sampled are from.

They figured out that a unique genetic variant, which is part of a noncoding region, is widespread in Native Americans across both American continents and it originated in Siberia. This implies that the first populations came into the Americas came from a single migration or multiple waves from a single source. This rules out the possibility that people came in waves of migrations from different sources. The following graph documents this:

Furthermore, the genetic diversity, as well as genetic similarity is very close to the Siberian groups tested. This supplements to existing archaeological and genetic evidence that the ancestors of native North and South Americans came by the northwest route.

Additional findings that are also interesting are that populations in the Andes and Central America are genetically similar. And populations from western South America showed more genetic variation than populations from eastern South America. And to appease the linguists out there, the populations more similar linguistically were also more similar genetically. Pretty cool, huh?

Anyways, please check out Blaine Bettinger, a.k.a, the Genetic Genealogist’s and Yann‘s posts on this, as well as my old post about the waves from Beringia, which collaborates with this finding.