Relative Rates of Evolution in the Coding and Control Regions of African mtDNAs

Abstract

Reduced median networks of African haplogroup L mitochondrial DNA (mtDNA) sequences were analyzed to determine the pattern of substitutions in both the noncoding control and coding regions. In particular, we attempted to determine the causes of the previously reported (Howell et al. 2004) violation of the molecular clock during the evolution of these sequences. In the coding region, there was a significantly higher rate of substitution at synonymous sites than at nonsynonymous sites as well as in the tRNA and rRNA genes. This is further evidence for the operation of purifying selection during human mtDNA evolution. For most sites in the control region, the relative rate of substitution was similar to the rate of neutral evolution (assumed to be most closely approximated by the substitution rate at 4-fold degenerate sites). However, there are a number of mutational hot spots in the control region, approximately 3% of the total sites, that have a rate of substitution greater than the neutral rate, at some sites by more than an order of magnitude. It is possible either that these sites are evolving under conditions of positive selection or that the substitution rate at some sites in the control region is strongly dependent upon sequence context. Finally, we obtained preliminary evidence for "nonideal" evolution in the control region, including haplogroup-specific substitution patterns and a decoupling between relative rates of substitution in the control and coding regions.

Clock debate: when times are a-changin': Time dependency of molecular rate estimates: tempest in a teacup

“…An important aspect that really deserves further investigation is that the pattern of synonymous and non-synonymous coding-region mutations does not appear to be uniform across different levels of the mtDNA phylogeny (Elson et al, 2004;Kivisild et al, 2006b;Howell et al, 2007). Evidence seems to point to the presence of purifying selection, in that young terminal branches show a relative excess of non-synonymous mutations.…”

“…Careful bookkeeping of a large number of reliable complete mtDNA sequences sampled across all major sections of the mtDNA phylogeny is indispensable for any progress in our understanding of the mutational process. A distinction between several categories of sites and mutations (Howell et al, 2007;Ingman and Gyllensten, 2007) is mandatory before any sort of time dependence of estimated rates can be formulated and evaluated.…”

Molecular clock debate: Time dependency of molecular rate estimates for mtDNA: this is not the time for wishful thinking

“…Instead, here, we focus on purifying (negative) selection and its consequences for the rate of sequence evolution. While purifying selection operates at the level of the germline (Stewart et al, 2008), it does not act instantaneously, and, instead, a substantial proportion of slightly deleterious mutations are lost continuously from the mtDNA gene pool over a prolonged period of time (Elson et al, 2004;Kivisild et al, 2006;Howell et al, 2007;Elson et al, submitted for publication). As a result of this selection acting throughout the human mtDNA phylogenetic tree, relatively more mutations have been lost in older branches (for example, mtDNAs from Africans) than in younger branches (for example, mtDNAs from Europeans).…”

“…There is a conundrum, because, according to standard population genetic models, drift tends to minimize or diminish the effects of purifying selection. (d) It is remarkable that the mtDNA control and coding regions do not appear to have evolved in lockstep (Howell et al, 2007), and the reasons for this 'decoupling' warrant investigation.…”

The Number of Albatross (Diomedeidae) Species

“…Furthermore, Christidis & Boles [9: 87] stated that Burg & Croxall [19] compared their data with other studies examining control region divergences in avian species and subspecies, but again these comparisons are limited in their instructiveness because different parts of the control region evolve at markedly different rates. (see also Howell et al [27], dealing with relative rates of evolution in the coding and control regions of African human DNA). Burg & Croxall [21] targeted a small, rapidly evolving section of the control region, but compared their results with some other studies that sampled complete or near complete control regions, including both highly conserved and variable regions.…”