Human Molecular Evolutive Rate, Time Dependency and Transient Polymorphism Effects Viewed Through Ancient and Modern Mitochondrial DNA Genomes.

Human evolutionary genetics gives a chronological framework to interpret the human history. It is based on the molecular clock hypothesis that suppose a straightforward relationship between the pace of the mutation rate and the evolutive rate with independence of other factors as demography dynamics. Analyzing ancient and modern human complete mitochondrial genomes we constate here that, along the time, the evolutive rate can be significantly slower or faster than the average germline mutation rate confirming a time dependence effect mainly attributable to changes in the effective population size of the human populations, with an exponential growth in recent times. We also detect that transient polymorphisms play a slowdown role in the evolutive rate deduced from haplogroup intraspecific trees. Finally, we propose the use of the most evolved lineages within haplogroups as a practical approach to correct these molecular clock mismatches.

The Out of East Asia model versus the African Eve model of modern human origins in light of ancient mtDNA findings

The first molecular model of modern human origins published in 1983 had the mtDNA phylogenetic tree rooted in Asia. This model was subsequently overlooked and superseded by the African Eve model in 1987 that was premised on the unrealistic infinite site assumption and the now failed molecular clock hypothesis. We have recently developed a new framework of molecular evolution, the maximum genetic diversity (MGD) hypothesis, which has in turn led us to discover a new model of modern human origins with the roots of uniparental DNAs placed in East Asia. While the African mtDNA Eve model has haplotype N as ancestral to R, our Asia model places R as the ancestor of all. We here examined ancient mtDNAs from the literature focusing on the relationship between N and R. The data showed that all three oldest mtDNAs were R with the 45000 year old Ust-Ishim a basal type and the two ~40000 year old samples sub-branch of R. Among the numerous mtDNAs of 39500-30000 year old, most were R subtype U and only two were N samples, the 39500 year old Oase1 and the 34425 year old Salkhit. These N types are basal and hence likely close to the root of N. These ancient DNA findings suggest that basal R is ~5000 years older than basal N, thereby confirming the East Asia model and invalidating the African Eve model.

Genetic equidistance at the nucleotide level

The genetic equidistance phenomenon was first discovered in 1963 by Margoliash and shows complex taxa to be all approximately equidistant to a less complex species in amino acid percentage identity. The result has been mis-interpretated by the ad hoc universal molecular clock hypothesis, and the much overlooked mystery was finally solved by the maximum genetic diversity hypothesis (MGD). Here, we studied 15 proteomes and their coding DNA sequences (CDS) to see if the equidistance phenomenon also holds at the CDS level. We performed DNA alignments for a total of 5 groups with 3 proteomes per group and found that in all cases the outgroup taxon was equidistant to the two more complex taxa species at the DNA level. Also, when two sister taxa (snake and bird) were compared to human as the outgroup, the more complex taxon bird was closer to human, confirming species complexity rather than time to be the primary determinant of MGD. Finally, we found the fraction of overlap sites where coincident substitutions occur to be inversely correlated with CDS conservation, indicating saturation to be more common in less conserved DNAs. These results establish the genetic equidistance phenomenon to be universal at the DNA level and provide additional evidence for the MGD theory.

The Genetic Equidistance Phenomenon at the Proteomic Level

The field of molecular evolution started with the alignment of a few protein sequences in the early 1960s. Among the first results found, the genetic equidistance result has turned out to be the most unexpected. It directly inspired the ad hoc universal molecular clock hypothesis that in turn inspired the neutral theory. Unfortunately, however, what is only a maximum distance phenomenon was mistakenly transformed into a mutation rate phenomenon and became known as such. Previous work studied a small set of selected proteins. We have performed proteome wide studies of 7 different sets of proteomes involving a total of 15 species. All 7 sets showed that within each set of 3 species the least complex species is approximately equidistant in average proteome wide identity to the two more complex ones. Thus, the genetic equidistance result is a universal phenomenon of maximum distance. There is a reality of constant albeit stepwise or discontinuous increase in complexity during evolution, the rate of which is what the original molecular clock hypothesis is really about. These results provide additional lines of evidence for the recently proposed maximum genetic diversity (MGD) hypothesis.