Relationships between Molecular Clock Deviations, Interactions, and Selection in Human mtDNA Haplogroups

Interactions between sites, selection and population effects, and other effects such as methylation of CpG groups all violate molecular clock assumptions, yet the molecular clock works surprisingly well. This study explores the relationship between these effects and the molecular clock, and seeks to understand the implications of these results in the context of recent studies of human mtDNA involving migration, environmental selection pressure, and other similar efforts. We present a maximum likelihood Poisson regression to the human mtDNA phylogenetic tree modeling a molecular clock, together with a similar computation of nonsynonymous to synonymous substitutions on each node, and their deviation from expectation determined from the entire phylogenetic tree. We show that the observed deviating nodes shows significant overlap between molecular clock counts and synonymous to nonsynonymous substitutions, primarily in leaf nodes and deep within the L-clades. This establishes connections between a mtDNA molecular clock model and prior studies also reporting deviations of nonsynonymous to synonymous substitution ratios between northern and temperate climes, but, at the finer level of analysis, we show that some of the groups of clades lumped by environment in previous studies are actually heterogeneous in their deviations, tending not to support environmental selection. This indicates that simple models of variation in rates fails to capture underlying systematic interactions between sites as well as other events that promote mutations, and that Poisson regression can be applied to identify clades marked by such deviations.