RT Journal Article
SR Electronic
T1 Epistasis and physico-chemical constraints contribute to spatial clustering of amino acid substitutions in protein evolution
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.05.237594
DO 10.1101/2020.08.05.237594
A1 Andrew M. Taverner
A1 Logan J. Blaine
A1 Peter Andolfatto
YR 2020
UL http://biorxiv.org/content/early/2020/08/05/2020.08.05.237594.abstract
AB The causes of rate variation among sites within proteins are as yet poorly understood. Here, we compare the spatial autocorrelation of non-synonymous substitutions among species within diverse phylogenetic groups: Saccharomyces, Drosophila, Arabidopsis, and primates. Across these taxa, we find that amino acid substitutions exhibit excess clustering that extends over a 20-30 codon length (10-20 Angstrom distance) scale. We show that these substitutions cluster more strongly and exhibit compensatory dynamics within species lineages but exhibit patterns of convergent evolution between lineages. We evaluate a simple model of thermodynamic constraints on protein folding and conclude that it is unable to recapitulate the observed spatial clustering of substitutions. While pairs of substitutions with the strongest epistasis tend to spatially cluster in these simulations, the magnitude and length scale are smaller than that observed in real data. Additionally, we show that the pattern of convergent substitution is also not expected under this model, suggesting it is likely caused by factors other than these simple thermodynamic constraints. Our results support a prevalent role for epistasis and convergent evolution in shaping protein evolution across the tree of life.Competing Interest StatementThe authors have declared no competing interest.