Looking for Darwin in all the wrong places: the misguided quest for positive selection at the nucleotide sequence level

Abstract

Recent years have seen an explosion of interest in evidence for positive Darwinian selection at the molecular level. This quest has been hampered by the use of statistical methods that fail adequately to rule out alternative hypotheses, particularly the relaxation of purifying selection and the effects of population bottlenecks, during which the effectiveness of purifying selection is reduced. A further problem has been the assumption that positive selection will generally involve repeated amino-acid changes to a single protein. This model was derived from the case of the vertebrate major histocompatibility complex (MHC), but the MHC proteins are unusual in being involved in proteinprotein recognition and in a co-evolutionary process of pathogens. There is no reason to suppose that repeated amino-acid changes to a single protein are involved in selectively advantageous phenotypes in general. Rather adaptive phenotypes are much more likely to result from other causes, including single amino-acid changes; deletion or silencing of genes or changes in the pattern of gene expression.

Pleistocene divergence across a mountain range and the influence of selection on mitogenome evolution in threatened Australian freshwater cod species

“…Reduced selective constraint on OXPHOS mitochondrial genes could be the result of relaxed metabolic constraints in the milder climate east of the GDR and/or reduced effectiveness of selection owing to reductions in effective population size associated with historical population bottlenecks (Hughes, 2007). In addition, lack of strong evidence of positive selection using the CODEML method may reflect low power because of relatively recent divergence of the coastal species and associated low polymorphism (Melo-Ferreira et al, 2014).…”

“…Whilst amino acid replacements in complex I (ND genes) tend to have minor effects on functional properties of amino acids, amino acid replacements in complex IV (COX genes) tend to have disproportionate effects on fitness, making COX genes typically the most highly conserved in the mitogenome (Zhang and Broughton, 2013). Although sites showing signatures of episodic positive selection detected in the Mary River cod may represent false positives that are in fact deleterious but not (yet) removed by selection because of low effective population size, investigation of candidate sites and adaptive processes in Mary River cod seems warranted (Hughes, 2007).…”

Distinguishing the effects of selection from demographic history in the genetic variation of two sister passerines based on mitochondrial–nuclear comparison

“…Whether the distribution of genetic variation is best explained by neutral or selective forces has fueled an extended debate in evolutionary biology (Hughes, 2007;Hahn, 2008). The neutral theory predicts that most genetic variants have few or no effects on fitness, and thus genetic variation is a function of mutation rate and population size (Kimura, 1983).…”

mtDNA haplotypes differ in their probability of being eliminated by a mass die-off in an abundant seabird

“…Fitness effects of small differences among mtDNA haplotypes have to be confirmed by independent data (Hughes, 2007). Experimental and field studies that assess differences in physiological performance between carriers of only slightly different mtDNA haplotypes under varying environmental conditions will be essential to validate our findings.…”