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

Abstract

The nearly neutral theory of molecular evolution posits variation among species in the effectiveness of selection. In an idealized model, the census population size determines both this minimum magnitude of the selection coefficient required for deleterious variants to be reliably purged, and the amount of neutral diversity. Empirically, an “effective population size” is often estimated from the amount of putatively neutral genetic diversity, and is assumed to also capture a species’ effectiveness of selection. The degree to which selection maintains preferred codons has the potential to more directly quantify the effectiveness of selection. However, 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 of codon bias, CAIS yields the expected relationship with adult vertebrate body mass. We demonstrate the use of CAIS correlations to show that the protein domains of more highly adapted vertebrate species evolve higher intrinsic structural disorder.

One million years of solitude: the rapid evolution of de novo protein structure and complex

“…This leads to a characteristic feature: a lack of stable tertiary structure when isolated, thus manifesting as intrinsically structural disorder (ISD) and extensive formation of intrinsic disordered regions (IDRs) or random coils. It is found that exquisitely adapted species contains more ISD domains (Weibel, et al 2023). ISD are also commonly found in proteins related to human genetic diseases (Midic, et al 2009; Vavouri, et al 2009).…”

Differential Retention of Pfam Domains Contributes to 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 et al 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

“…It is calculated with respect to a standardized set of amino acid frequencies and therefore, by construction, also avoids confounding with amino acid frequencies. Weibel et al (2024) found that high-CAIS species have higher proteome-wide intrinsic structural disorder, demonstrating the metric's utility for revealing how the effectiveness of selection shapes fundamental physical properties of macromolecules.…”

“…By estimating Ne 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 larger effective population sizes also show stronger synonymous codon usage bias due to selection (Akashi, 1996;Galtier et al, 2018;Subramanian, 2008;Weibel et al, 2024). Here we ask whether differences among species in amino acid frequencies can similarly 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 examine whether final proteome-wide amino acid frequenciesrather than rates of fluxare correlated with Ne. We quantify Ne using a recently developed metric, the Codon Adaptation Index of Species (CAIS; Weibel et al, 2024). CAIS captures the fraction of synonymous sites within the genome for which selection is able to overcome drift.…”