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.


Marvin D. said...

Autism: The Eusocial Hominid Hypothesis


ASDs (autism spectrum disorders) are hypothesized as one of many adaptive human cognitive variations that have been maintained in modern populations via multiple genetic and epigenetic mechanisms. Introgression from "archaic" hominids (adapted for less demanding social environments) is conjectured as the source of initial intraspecific heterogeneity because strict inclusive fitness does not adequately model the evolution of distinct, copy-number sensitive phenotypes within a freely reproducing population.

Evidence is given of divergent encephalization and brain organization in the Neanderthal (including a ~1520 cc cranial capacity, larger than that of modern humans) to explain the origin of the autism subgroup characterized by abnormal brain growth.

Autism and immune dysfunction are frequently comorbid. This supports an admixture model in light of the recent discovery that MHC alleles (genes linked to immune function, mate selection, neuronal "pruning," etc.) found in most modern human populations come from "archaic" hominids.

Mitochondrial dysfunction, differential fetal androgen exposure, lung abnormalities, and hypomethylation/CNV due to hybridization are also presented as evidence.

Reuel said...

The link goes to a website with big claims, including that MHC/HLA class I is required for "normal" brain development. However, humans and other animals without functioning immune systems, i.e., no class I or no class II or no innate immune response, seem behaviorally and intellectually normal. This apparently refutes any dependence of brain development on the immune system.