Neanderthals had ancestral Microcephalin gene

Evans et al. had previously proposed that the derived MCPH1 allele had entered the modern human gene pool by Neandertals. This paper tests this by looking at a 50,000 year BP Neandertal, finding them to have the ancestral allele, thus weakening the case for introgression.

The authors write:

Evans and colleagues proposed that haplogroup D originated from a lineage separated from modern humans for 1.1 million years and introgressed into the human gene pool by 37,000 years ago, probably from a Neanderthal stock [4].

However, simulation approaches have shown that two key hypotheses of this model, namely positive selection and admixture, can be relaxed as long as Eurasia was settled from an African population that was both subdivided and under expansion [5]. Interestingly, variation in neurocranial geometry have recently suggested significant levels of geographic structure among early modern humans from Africa [6]. In addition, no direct empirical evidence supports a third key component of the model, ie. that Neanderthals carried alleles of the D haplogroup.

This is a great paper in view of the recent controversy about modern human-Neandertal admixture. I have been on the skeptic camp, and this certainly strengthens my African structure thesis.

Here is how the authors try to explain the deep divergence between the ancestral and derived haplotypes:

There is a broad agreement that the contribution of archaic Homo populations to the modern gene pool, if any, must have been very limited [33], [34]. Different lines of evidence concur to suggest that the dispersal of anatomically modern humans from Africa was accompanied by repeated founder effects [35]–[38]. If these founder effects were drastic, most or all gene genealogies should actually be shallow, and hence the occurrence of ancient splits would imply some degree of introgression from archaic human forms. However, different consequences would be expected if only mild founder effects occurred when anatomically modern humans moved out of Africa. Under these conditions, gene trees would have a strong random component, and a certain fraction thereof, even in the absence of selection, would show two highly divergent major lineages [39]. The likelihood of finding gene genealogies with a very old common ancestor and very differentiated lineages would be even higher if the source African population was subdivided and structured genetically before dispersal, which is what most studies clearly suggest [40]–[43]. These theoretical considerations are actually matched by consistent results in simulation studies [5], [34], [44] and by variation in neurocranial geometry, suggesting significant levels of geographic structure among early modern humans from Africa [6].

One more piece of evidence in favor of the idea that seemingly archaic DNA in modern Eurasians is not due to the more fashionable "Neandertal introgression" but to ancient African population structure.

PLoS ONE 10.1371/journal.pone.0010648

The Microcephalin Ancestral Allele in a Neanderthal Individual

Martina Lari et al.

Background
The high frequency (around 0.70 worlwide) and the relatively young age (between 14,000 and 62,000 years) of a derived group of haplotypes, haplogroup D, at the microcephalin (MCPH1) locus led to the proposal that haplogroup D originated in a human lineage that separated from modern humans >1 million years ago, evolved under strong positive selection, and passed into the human gene pool by an episode of admixture circa 37,000 years ago. The geographic distribution of haplogroup D, with marked differences between Africa and Eurasia, suggested that the archaic human form admixing with anatomically modern humans might have been Neanderthal.

Methodology/Principal Findings
Here we report the first PCR amplification and high- throughput sequencing of nuclear DNA at the microcephalin (MCPH1) locus from Neanderthal individual from Mezzena Rockshelter (Monti Lessini, Italy). We show that a well-preserved Neanderthal fossil dated at approximately 50,000 years B.P., was homozygous for the ancestral, non-D, allele. The high yield of Neanderthal mtDNA sequences of the studied specimen, the pattern of nucleotide misincorporation among sequences consistent with post-mortem DNA damage and an accurate control of the MCPH1 alleles in all personnel that manipulated the sample, make it extremely unlikely that this result might reflect modern DNA contamination.

Conclusions/Significance
The MCPH1 genotype of the Monti Lessini (MLS) Neanderthal does not prove that there was no interbreeding between anatomically archaic and modern humans in Europe, but certainly shows that speculations on a possible Neanderthal origin of what is now the most common MCPH1 haplogroup are not supported by empirical evidence from ancient DNA.

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