genetic drift & genome architecture

Koonin EV 2009 Darwinian evolution in the light of genomics. Nucl Acids Res 37:1011-1034.

• Kimura and others realized that mutations that were (nearly) neutral at the time of fixation were not indifferent to evolution
• such mutations comprised the pool of variation that can be tapped into by natural selection under changed conditions
• a phenomenon that could be potentially important for macroevolution

• expression level or, more precisely, the rate of translational events is indeed the dominant determinant of the sequence evolution rate
• the MIM hypothesis could additionally explain the rather puzzling but consistent and strong positive correlation between the rates of evolution in synonymous and non-synonymous positions (dN and dS, respectively) of protein-coding sequences
• this correlation is likely to be a consequence of the slow evolution in both classes of sites in highly expressed genes which, in the case of synonymous sites, is likely to be caused by selection for codons that minimize mistranslation

• the primary driving force of purifying selection might not be the maintenance of a biological function but rather prevention of non-specific deleterious effects of a misfolded protein