Bioinformatický seminár

Tue 30 Apr. 2013, 17:20

Title: Michael S. Breen et al. (2012) Epistasis as the primary factor in molecular evolution
Speaker: Katka Juríková

The main forces directing long-term molecular evolution remain obscure. A sizable
fraction of amino-acid substitutions seem to be fixed by positive selection, but 
it is unclear to what degree long-term protein evolution is constrained by
epistasis, that is, instances when substitutions that are accepted in one
genotype are deleterious in another. Here we obtain a quantitative estimate of
the prevalence of epistasis in long-term protein evolution by relating data on
amino-acid usage in 14 organelle proteins and 2 nuclear-encoded proteins to their
rates of short-term evolution. We studied multiple alignments of at least 1,000
orthologues for each of these 16 proteins from species from a diverse
phylogenetic background and found that an average site contained approximately
eight different amino acids. Thus, without epistasis an average site should
accept two-fifths of all possible amino acids, and the average rate of amino-acid
substitutions should therefore be about three-fifths lower than the rate of
neutral evolution. However, we found that the measured rate of amino-acid
substitution in recent evolution is 20 times lower than the rate of neutral
evolution and an order of magnitude lower than that expected in the absence of
epistasis. These data indicate that epistasis is pervasive throughout protein
evolution: about 90 per cent of all amino-acid substitutions have a neutral or
beneficial impact only in the genetic backgrounds in which they occur, and must
therefore be deleterious in a different background of other species. Our findings
show that most amino-acid substitutions have different fitness effects in
different species and that epistasis provides the primary conceptual framework to
describe the tempo and mode of long-term protein evolution.