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Title: Epistatic contributions promote the unification of incompatible models of neutral molecular evolution
We introduce a model of amino acid sequence evolution that accounts for the statistical behavior of real sequences induced by epistatic interactions. We base the model dynamics on parameters derived from multiple sequence alignments analyzed by using direct coupling analysis methodology. Known statistical properties such as overdispersion, heterotachy, and gamma-distributed rate-across-sites are shown to be emergent properties of this model while being consistent with neutral evolution theory, thereby unifying observations from previously disjointed evolutionary models of sequences. The relationship between site restriction and heterotachy is characterized by tracking the effective alphabet dynamics of sites. We also observe an evolutionary Stokes shift in the fitness of sequences that have undergone evolution under our simulation. By analyzing the structural information of some proteins, we corroborate that the strongest Stokes shifts derive from sites that physically interact in networks near biochemically important regions. Perspectives on the implementation of our model in the context of the molecular clock are discussed.  more » « less
Award ID(s):
1943442
PAR ID:
10199532
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
Proceedings of the National Academy of Sciences
Volume:
117
Issue:
11
ISSN:
0027-8424
Page Range / eLocation ID:
5873 to 5882
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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