Saturday, March 31, 2012

Monkey’s Uncle? Your HLA might be Neanderthal

Humans’ genomes are extremely similar to those of other primates because the species diverged relatively recently, approximately 6 million years ago in the case of our nearest cousins, Chimpanzees. Modern humans and Denisovans separated 250,000 years ago (10,000 generations). With the recent sequencing of extinct, ancient hominids, such as Neanderthals and their Denisovan relatives, it was realized that up to 6% of the genomes of humans now in Europe and Asia derive from these older lineages.

HLA genes are by far the most polymorphic within the human genome, with thousands of variants (alleles). Here, investigators first identified one particular HLA allele, HLA-B*73:01, as being more similar to homologous Chimpanzee alleles than other human HLA-B alleles. This allele diverged from other HLA-B alleles 16 million years ago, before the separation of humans and Chimps, and was lost from the majority of modern humans. Its reappearance in the human genome was most likely, they reckoned, a result of “introgression”, introduction from ancient humans such as Neanderthal. An alternative model, which computer simulations indicate is 100 times less probable, is that this allele came out of Africa late

They also simply “typed” (sequenced and matched) the most important HLA loci, HLA-A, -B and –C from 1 Denisovan and 2 Neanderthal subjects. Surprisingly, most of these archaic HLA alleles were identical to common HLA types of modern humans. HLA-A2, the most widespread allele at the HLA-A locus, was shared with and might have been acquired from Denisovans. Putative archaic HLA-A alleles are now more common in China and Europe than in Africa (Figure, from fig. 4d). The authors conclude that although a small minority of our genomes overall derived from archaic humans, about half of our HLA was acquired through interbreeding between modern humans migrating out of Africa and locally established archaic humans. These archaic alleles conferred fitness in the new environment, e.g., pathogen and allergen resistance, and so outcompeted and displaced previous human HLA alleles.

The shaping of modern human immune systems by multiregional admixture with archaic humans. Abi-Rached et al. Science. 2011 Oct 7;334(6052):89-94.