MCPH1 gene could have a Neanderthal origin.

Evidence that the adaptive allele of the brain size gene microcephalin introgressed into Homo sapiens from an archaic Homo lineage
Patrick D. Evans*,†,‡, Nitzan Mekel-Bobrov*,†,‡, Eric J. Vallender*,†,‡, Richard R. Hudson§, and Bruce T. Lahn*,†,¶ 2006

At the center of the debate on the emergence of modern humans and their spread throughout the globe is the question of whether archaic Homo lineages contributed to the modern human gene pool, and more importantly, whether such contributions impacted the evolutionary adaptation of our species. A major obstacle to answering this question is that low levels of admixture with archaic lineages are not expected to leave extensive traces in the modern human gene pool because of genetic drift. Loci that have undergone strong positive selection, however, offer a unique opportunity to identify low-level admixture with archaic lineages, provided that the introgressed archaic allele has risen to high frequency under positive selection. The gene microcephalin (MCPH1) regulates brain size during development and has experienced positive selection in the lineage leading to Homo sapiens. Within modern humans, a group of closely related haplotypes at this locus, known as haplogroup D, rose from a single copy ≈37,000 years ago and swept to exceptionally high frequency (≈70% worldwide today) because of positive selection. Here, we examine the origin of haplogroup D. By using the interhaplogroup divergence test, we show that haplogroup D likely originated from a lineage separated from modern humans ≈1.1 million years ago and introgressed into humans by ≈37,000 years ago. This finding supports the possibility of admixture between modern humans and archaic Homo populations (Neanderthals being one possibility). Furthermore, it buttresses the important notion that, through such adminture, our species has benefited evolutionarily by gaining new advantageous alleles. The interhaplogroup divergence test developed here may be broadly applicable to the detection of introgression at other loci in the human genome or in genomes of other species.

I think this would really need someone to test the Neanderthal DNA they’ve got to confirm this.  But according to John Hawkes this copuld prove tricky.

5 responses to “MCPH1 gene could have a Neanderthal origin.

  1. I find somewhat odd that an allele that is widespread among all humans save Sud-Saharan Africans would be Neanderthal in origin. Per the rapid coastal migration model, most “Eurasians” (wide meaning of the term) would not have got any contact with Neanderthals then and there is no reason to think that an introgressed gene picked upon migraion to West Eurasia would have easily become so widespread among East Asians or even Australian Aboriginals.

    The only reasonable explanation (if the gene is actually Neanderthal) could be that the rapid coastal migration model is partly wrong and that “Eurasian” founding parents would have first lived for a while side by side with Neanderthals in West Asia before being displaced into India precisely by Neanderthal expansion into West and Central Asia.

    Not impossible, IMHO. But the simplest explanation is that MCPH1 is just an OOA founder effect. There’s no reason, except gratuitous speculation, to think it is a Neanderthal introgression anyhow.

    As demonstrated by Mekel-Bobrov et al, 2007 (doi:10.1093/hmg/ddl487), the adaptative value of MCPH1, as well as that of ASPM, both hyped by some people not long ago, seems null. But the rebuttal did not get so much attention, probably because it did not help to support “Neanderthal introgression” hypothesis nor racial supremacy discourses.

    It is probably just a founder effect.

  2. You got Neanderthals right into Siberia, so that would account for the 70% frequency in the world population; it probably just missed out the SS Africans and Australoids.

  3. Latest on MCPH1 et al.

    Recently-derived variants of brain-size genes ASPM, MCPH1, CDK5RAP and BRCA1 not associated with general cognition, reading or language

    Timothy C. Bates et al.


    Derived changes in genes associated with primary microcephaly (MCPH) have been suggested to be “currently sweeping to fixation” i.e., increasing in frequency in most populations, with the likely outcome that the derived allele will completely displace the ancestral allele over time. Possible causes for this sweep include effects on human reasoning and language. Here we test the hypothesis that these derived alleles are associated with current variation in spoken or written language and related traits. The association of derived alleles of the ASPM, MCPH1, CDK5RAP2 and BRCA1 genes was tested against well-validated measures of dyslexia, specific language impairment, working memory, IQ, and head-size in a family-based association study of over 1776 subjects from 789 families of twins. No evidence for association was found for any gene to any trait. The results strongly did not support the hypothesis that derived alleles in MCPH-related genes are related to the evolution of human language or cognition.

    Results were compatible with the alternate hypothesis, suggesting that adaptations in these genes associated with a dramatic increase in brain size have long since reached fixation and are now maintained by stabilizing selection.

  4. “The only reasonable explanation (if the gene is actually Neanderthal) could be that the rapid coastal migration model is partly wrong”.

    I’m sure I don’t need to remind you of my views on that, Luis. As Mathilda said, “You got Neanderthals right into Siberia”. I’ve expanded on my views regarding the coastal route on in the Australian origins post if you’re interested.

  5. Well, I can’t say much more. The results are somewhat contradictory but the overall impression is that the alelles are neutral or nearly so. I am glad that you posted also the other studies, as this way it’s best reflected the different sides of the debate.

    You got Neanderthals right into Siberia, so that would account for the 70% frequency in the world population; it probably just missed out the SS Africans and Australoids.

    I am not aware that Australoids are missing this widespread Eurasian gene, the papers only mention Sud-Saharans. I may be missing something though.

    In any case the max. range of Neanderthals, including Altai (the Siberian region that represents the easternmost range of this species) approaches pretty well (maybe excluding Iran) the prehistorical range of West Eurasians, aka Caucasoids. The East Asian expansion in Central Asia (and Altai should be included in this region for anthropological purposes) seems to be quite recent, beginning with the Turkic expansion some 2000 yeas ago.

    The Neanderthal range does not seem to explain the distribution of this alelle among non-Caucasian Eurasians, unless maybe it was such an excellent gene that it introgressed massively into all populations that had minimal contanct with West Eurasians.

    I see no reason to exclude Sud-Saharan Africans from this logic nor to include Australian Aborigines. Regarding Sud-Saharan Africa, contact has existed across the Sahara, along the Nile and through the Red Sea and in some areas of the Sahel West Eurasian clades are important. And these contacts are at least as important as the ones that existed with East Asiaa nd should account for any adaptative gene having penetrated into Tropical Africa at least as much as into East Asia; the lactase persistence genes are a good example of West Eurasian originated introgression of a truly adaptative gene, and these are at least as important in Tropical Africa as they are in East Asia, if not more.

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