AN IMPROVED METRIC OF CODON ADAPTATION SHOWS SELECTION FOR DISORDER IN VERTEBRATE PROTEIN DOMAINS

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.