Evolution is not uniform along protein sequences

Abstract

Amino acids evolve at different speeds within protein sequences, because their functional and structural roles are different. However, the position of an amino-acid within the sequence is not known to influence this evolutionary speed. Here we discovered that amino-acid evolve almost twice faster at protein termini than in their centre, hinting at a strong topological bias along the sequence length. We further show that the distribution of functional domains and of solvent-accessible residues in proteins readily explain how functional constrains are weaker at their termini, leading to the observed excess of amino-acid substitutions. Finally, we show that methods inferring sites under positive selection are strongly biased towards protein termini, suggesting that they may confound positive selection with weak negative selection. These results suggest that accounting for positional information should improve evolutionary models.

Gene protein sequence evolution can predict the rapid divergence of ovariole numbers inDrosophila

“…Fifth, while expression breadth, and thus tau (Yanai et al 2005), provides an effective proxy for gene pleiotropy (Mank and Ellegren 2009; Meisel 2011; Assis et al 2012; Whittle et al 2021), further studies of pleiotropy from analyses of gene protein connectivity networks (Kim et al 2007; Masalia et al 2017) among species within this clade may also provide insights the selection pressures affecting ovariole-related genes. As part of such studies, a valuable aspect may include evaluation of the position of amino acid substitutions with respect to degree of protein-folding and terminal regions (Echave et al 2016; Jumper et al 2021; Bricout et al 2022). Finally, an especially valuable route for further research includes studies in the Hawaiian Drosophila, an expansive taxonomic group that exhibits marked phenotypic diversity in sexual characteristics ranging from behaviours to ovariole numbers (Carson 1997; Singh and Singh 2014), (Sarikaya et al 2019).…”