Abstract
We use first principles of population genetics to model the evolution of proteins under persistent positive selection (PPS). PPS may occur when organisms are subjected to persistent environmental change, during adaptive radiations, or in host–pathogen interactions. Our mutation–selection model indicates protein evolution under PPS is an irreversible Markov process, and thus proteins under PPS show a strongly asymmetrical distribution of selection coefficients among amino acid substitutions. Our model shows the criteria (where ω is the ratio of nonsynonymous over synonymous codon substitution rates) to detect positive selection is conservative and indeed arbitrary, because in real proteins many mutations are highly deleterious and are removed by selection even at positively selected sites. We use a penalized-likelihood implementation of the PPS model to successfully detect PPS in plant RuBisCO and influenza HA proteins. By directly estimating selection coefficients at protein sites, our inference procedure bypasses the need for using ω as a surrogate measure of selection and improves our ability to detect molecular adaptation in proteins.
Highlights
Understanding how natural selection acts on molecular sequences has long been a pursuit of evolutionary biology
The values of Fi,j,k are drawn from random distributions to produce sharp amino acid profiles as in real proteins
Mutation-selection models of codon substitution have been successfully used to study the distribution of selection coefficients in proteins (Rodrigue et al, 2010; Tamuri et al, 2014), to detect selection shifts during adaptation (Parto and Lartillot, 2017), shifting balance (Jones et al, 2016), and to understand protein evolution given structural constraints (Youssef et al, 2020)
Summary
Understanding how natural selection acts on molecular sequences has long been a pursuit of evolutionary biology. For a sample of protein-coding sequences from various species, the ratio between the number of substitutions at non-synonymous sites (which are under selection) and at synonymous sites (which are under weak or no selection) should approximately follow the dynamics of Eq 1 (Nielsen and Yang, 2003). This ratio, commonly known as ω = dN /dS, is widely used as a test of molecular adaptation in proteins, with ω > 1, ω = 1, and ω < 1 interpreted as evidence of molecular adaptation (positive selection), neutral evolution, and purifying selection respectively
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