The protein domains of vertebrate species in which selection is more effective have greater intrinsic structural disorder

Abstract

The effectiveness of selection varies among species. It is often estimated by means of an 'effective population size' based on neutral polymorphism, but this is confounded in complex ways with demography. The strength of codon bias more directly pertains to how well adaptation at many sites can be maintained in the face of deleterious mutations, but past metrics that compare codon bias across species are confounded by among-species variation in %GC content and/or amino acid composition. Here we propose a new Codon Adaptation Index of Species (CAIS) that corrects for both confounders. Unlike previous metrics, CAIS yields the expected relationship with adult vertebrate body mass. As an example of the use of CAIS, we ask whether protein domains evolve lower intrinsic structural disorder (ISD) when present in more exquisitely adapted species, as expected given that ISD is higher in eukaryotic proteomes than prokaryotic proteomes. Using phylogenetically corrected linear models, we find, contrary to expectations, that the ISD of a given protein domain evolves to be higher when in well-adapted species. This effect is stronger in young protein domains but is also present in ancient domains.

Universal and taxon-specific trends in protein sequences as a function of age

“…There is no significant change in ISD over "ancient" pfams (those that emerged prior to the last eukaryotic common ancestor (LECA), which is estimated to have existed around 2101 MYA). This does not mean that ISD is static; for example, the same domain in more exquisitely adapted vertebrates has higher ISD (Weibel et al 2020).…”

Differential retention of Pfam domains creates long-term evolutionary trends

“…While the evolution of amino acid frequencies can be rapid enough to keep pace with changes in nucleotide composition (Brbić et al 2015), epistatic effects might lead to significant deceleration beyond a certain point (Vieira-Silva and Rocha 2008). Vertebrate species with higher effective population size tend to evolve higher ISD (Weibel et al 2020), which is the opposite direction to what would be needed to produce the phylostratigraphy trends under the assumption that most ancestral lineages had high population size. While ISD was not directly assessed, long-term directional trends in amino acid frequencies via descent with modification have been inferred during early evolution (Groussin, Boussau, and Gouy 2013), as well as during the more recent evolution of cold tolerance (Fontanillas et al 2017; Lecocq et al 2021).…”

The effectiveness of selection in a species affects the direction of amino acid frequency evolution

“…By estimating N e from neutral genetic diversity, Lynch and Conery (2003) used the nearly neutral theory to explain why species with smaller effective population sizes have more bloated genomes. Species with large effective population sizes also show stronger selective preferences among synonymous codons than those with small population sizes (Akashi, 1996; Galtier et al, 2018; Subramanian, 2008; Weibel et al, 2020). Here we ask whether differences among species in amino acid frequencies can also be explained by the nearly neutral theory of evolution, and if so, what this tells us about the biophysical basis of intrinsic selective preferences.…”

“…We compare recent fluxes in rodent vs. in primate lineages, as we know that selection is more effective in the former (Eőry et al, 2010; Halligan et al, 2010; Keightley et al, 2005), corresponding to much larger census population sizes with greater neutral genetic diversity (Phifer-Rixey et al, 2012; Tenesa et al, 2007). Second, we use a recently developed metric, the Codon Adaptation Index of Species (CAIS; Weibel et al, 2020), to quantify how the effectiveness of selection influences outcomes across a broader range of vertebrate species, i.e. we ask whether this metric predicts amino acid frequencies.…”

“…Our second approach looks at a broader range of vertebrate species, and scores outcomes (in the form of amino acid frequencies) rather than process (identifying and counting specific substitutions as in our first, flux approach). We relate amino acid frequencies to a species’ effectiveness of selection, measuring the latter by the Codon Adaptation Index of Species (CAIS; Weibel et al, 2020). CAIS is a measure of a species’ codon bias that has been corrected for the %GC content of the species and calculated with respect to a standardized set of amino acid frequencies.…”