Saturday, November 12, 2011

Travels and meetings of ancient humans

Australians branched from Out-of-Africans long before Europeans and Asians diverged.

An interesting caveat to the Out-of-Africa origin for modern humans is that perhaps 4% of our genomes apparently comes from archaic humans these modern African emigrants encountered in Europe and Asia- the Neaderthals and a recently discovered more eastern relative of the Neanderthals, the Denisovans of the Altai mountains, a bit south of Novosibirsk, of whom a couple of bones and DNA are known, but not much else.

Which parts of our genomes? Well, a recent paper claims that up to 60% of some modern immunological genes stem from these archaic genomes, suggesting that pathogens encountered outside Africa may have been novel and subjected emigrating humans to selective pressure that the resident proto-humans had already mastered, genetically speaking.

The human leukocyte antigen (HLA) genes are an interesting group in several ways. Their function is to expose small bits of pathogen-derived proteins that the leukocyte (an antigen presenting cell) has been chewing on on its outside surface, so that other parts of the immune system (like killer T-cells) can "read" what this first line of defense is seeing and responding to. It is a very elegant system, finely balanced between over-active auto-immunity and prompt action against foreign pathogens.

No single (HLA) protein is ideally suited to hold and display the large variety of foreign proteins that the immune system may encounter, so we have three: HLA-A, -B, and -C. These proteins are additionally highly variable through human populations and vary quickly with evolution, as the pathogens we meet change quickly as well. It is highly beneficial to have different alleles of each gene from one's parents (i.e., be heterozygous), and women are thought to be able subconsciously to detect whether the men they are mating with have different HLA alleles from themselves. Wow!

This kind of selection is called "balancing" selection, where the optimal genetic population structure is not one ideal allele of one gene, (i.e. the "perfect", or evolutionarily "best" gene), but a diversity of different alleles. This theme is likely to be highly significant in psychological characteristics as well as immunological ones.

At any rate, one research group recently used the available DNA sequences from Neanderthals and their cousins, the Denisovan archaic humans, to determine that some of their HLA alleles are not closely related to anything found in Africa today, and yet make up a substantial portion in many non-African human populations. Which is to say that humans today outside of Africa obtained significant immunological diversity from their mating with these archaic humans.

HLA-A 11(Denisovan) Up to 48% of populations centered on South China and Papua New Guinea.
HLA-B 73(Denisovan) Up to 4% of people in west Asia, centered on Afghanistan.
HLA-B 07:02 (Neanderthal) Up to 17% of people centered on Britain and Scandinavia.
HLA-B 51:01 (Neanderthal) Up to 18% of people centered on Eastern Turkey.
HLA-C 12:02 (Denisovan) Up to 11% of populations centered on Mumbai and Japan.
HLA-C 15(Denisovan) Up to 19% of populations centered on Pakistan and northern Australia.
HLA-C 7:02 (Neanderthal) Up to 30% of populations centered on Moscow and south China.
HLA-C 16:02 (Neanderthal) Up to 5% of populations centered on Iran.

Geographic distribution of one archaic HLA human allele.

Once the recent African origin of modern humans became clear, many other questions arose- how, when, where, and who? Upon leaving Africa, which groups went where and when? A second paper gives quantitative evidence, from one partial Australian aboriginal genome sequence, that this group split off long before the Europeans and other Asians separated.

Geographically, one would suspect that, like the Native Americans and Polynesians, Aboriginal Australians would be at the end of the line of human divergence, separating at very late times from nearby groups in Southern Asia (model A). Morphologically, however, Aboriginal Australians don't fit this template at all, having closer resemblances with Africans than with the geographically intervening groups such as the Polynesians (model B).

The genetics bear out the latter story. These researchers used a museum sample of Aboriginal hair, apparently to evade problems of genetic contamination with Europeans, to sequence about 60% of one genome. They also sequenced three Han Chinese genomes and of course had numerous other genomes to work with by this point (about 1,220 individual sets of snp data).

The data took the form of snps- single base pair alterations/mutations from the common sequence that can be used forensically to track lineages, since descendents share the alterations of their ancestors than those of non-ancestors. All this data (14,000 snp sites) was thrown into a statistical program that spat out expected rates of snp identities under various lineage models.

The numerical differences / output are impossible for a non-expert to comment on, but they claim high statistical significance for their result that model B beats model A by a long shot. They also estimate the time from African/Australian divergence at 2750 generations, or about 70,000 years ago (using a generation time of ~27 years, apparently). In contrast, the European and Asian lineages diverged less than half as long ago, about 30,000 years ago. Indeed, this second divergence would seem to be an entirely different dispersal event that may have swept previously resident Australian-lineage peoples from all areas of Asia other than the far reaches of Papua New Guinea and Australia which become isolated about this time by rising sea levels. (And the Aeta in the Philippines.)

The global map they offer is:

Lastly, these scientists are also very excited by the possible mixing of Neanderthal or Denisovan genomes with those of the future Australians. Interestingly, they find the same degree of Neanderthal mixing in their Australian genome as in European and Asian genomes, indicating that, rather than mating with the final Neanderthal holdouts in Southern Europe, the mixing we observe genetically took place soon after the first migrations out of Africa.

For the Denisovan DNA, they find higher amounts of mixture (unspecified, but probably ~4%) in their Australian genome than in virtually any other group, indicating that this early migration had especially close contact with these archaic humans.

It is fascinating to see our origins come into clearer focus through the analysis of new data. Old conflicts like the early (regional speciation) versus late out-of-Africa theories are now definitively resolved, finding a bit of truth in both, but mostly favoring the later out-of-Africa theory. The travels of our ancestors, while hardly tracked with GPS, are slightly less obscure, indicating that native Australians have, in the words of these authors, "one of the oldest continuous population histories outside sub-Saharan Africa today", dating back roughly 50,000 years.

"If a country or region has no power to devalue, and if it is not the beneficiary of a system of fiscal equalisation, then there is nothing to stop it suffering a process of cumulative and terminal decline leading, in the end, to emigration as the only alternative to poverty or starvation."
  • And Krugman: "If you were part of the dialogue in the late 80s and early 90s, it became clear that the euro was best understood as a plot by Italian technocrats to get themselves German central bankers. This was not, it turns out, a good idea."

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