Abstract
BackgroundThe 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 FindingsHere 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/SignificanceThe 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.
Highlights
The gene microcephalin or MCPH1 is a critical regulator of brain size
In the hypervariable region 1 (HVR-I) region, 106 out of 120 clone sequences were Neanderthal-specific and showed the same motif previously reported for the Monti Lessini (MLS) sample [8] (Table 1, Figure S1); the remaining 14 clones shared a modern human motif that matched with the profile obtained from one lab members, and the one (LL) who handled the samples most recently (Table 1, Figure S1)
Our data show that the vast majority of clones amplified from the MLS Neanderthal extract contain the ancestral allele of MCPH1
Summary
The gene microcephalin or MCPH1 is a critical regulator of brain size. In humans, homozygosis for loss-of-function mutations in this gene causes a condition known as primary microcephaly, characterized by a severe reduction in brain volume (3- to 4fold) and by a retention of the overall neuroarchitecture, without evident defects outside of the brain [1]. Microcephalin has been proposed as the target of positive selection in the evolutionary lineage leading from ancestral primates to humans [2] This observation, coupled with the fact that this gene is a critical regulator of brain size, suggests that the molecular evolution of microcephalin may have contributed to the phenotypic evolution of the human brain [2]. 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
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