December 11, 2010

Early Homo mtDNA relic in the human nuclear genome

PLoS ONE 5(12): e14278. doi:10.1371/journal.pone.0014278

Genome Digging: Insight into the Mitochondrial Genome of Homo

Igor V. Ovchinnikov, Olga I. Kholina

A fraction of the Neanderthal mitochondrial genome sequence has a similarity with a 5,839-bp nuclear DNA sequence of mitochondrial origin (numt) on the human chromosome 1. This fact has never been interpreted. Although this phenomenon may be attributed to contamination and mosaic assembly of Neanderthal mtDNA from short sequencing reads, we explain the mysterious similarity by integration of this numt (mtAncestor-1) into the nuclear genome of the common ancestor of Neanderthals and modern humans not long before their reproductive split.

Principal Findings
Exploiting bioinformatics, we uncovered an additional numt (mtAncestor-2) with a high similarity to the Neanderthal mtDNA and indicated that both numts represent almost identical replicas of the mtDNA sequences ancestral to the mitochondrial genomes of Neanderthals and modern humans. In the proteins, encoded by mtDNA, the majority of amino acids distinguishing chimpanzees from humans and Neanderthals were acquired by the ancestral hominins. The overall rate of nonsynonymous evolution in Neanderthal mitochondrial protein-coding genes is not higher than in other lineages. The model incorporating the ancestral hominin mtDNA sequences estimates the average divergence age of the mtDNAs of Neanderthals and modern humans to be 450,000–485,000 years. The mtAncestor-1 and mtAncestor-2 sequences were incorporated into the nuclear genome approximately 620,000 years and 2,885,000 years ago, respectively.

This study provides the first insight into the evolution of the mitochondrial DNA in hominins ancestral to Neanderthals and humans. We hypothesize that mtAncestor-1 and mtAncestor-2 are likely to be molecular fossils of the mtDNAs of Homo heidelbergensis and a stem Homo lineage. The dN/dS dynamics suggests that the effective population size of extinct hominins was low. However, the hominin lineage ancestral to humans, Neanderthals and H. heidelbergensis, had a larger effective population size and possessed genetic diversity comparable with those of chimpanzee and gorilla.


aargiedude said...

Dienekes, I'm curious as to what populations you used to generate the file for your standard K=10, 692 samples, 36 population barplot of Eurasian samples. You said with r2 = 0.3 you obtained 177K SNPs. With r2 = 0.3 I got 155K SNPs. But I used all the 692 samples to generate When I used just a few populations, I got 176K SNPs.

Dienekes said...

I did all my pruning on the HGDP dataset of 940 individuals, as that has the broadest human coverage. I don't reprune from scratch every time I choose another subset of populations, hence all my (recent) analyses invariably use 177k SNPs. This helps things relatively comparable between them.