Abstract
Various structural and functional constraints govern the evolution of protein sequences. As a result, the relative rates of amino acid replacement among sites within a protein can vary significantly. Previous large-scale work on Metazoan (Animal) protein sequence alignments indicated that amino acid replacement rates are partially driven by a complex interaction among three factors: intrinsic disorder propensity; secondary structure; and functional domain involvement. Here, we use sequence-based predictors to evaluate the effects of these factors on site-specific sequence evolutionary rates within four eukaryotic lineages: Metazoans; Plants; Saccharomycete Fungi; and Alveolate Protists. Our results show broad, consistent trends across all four Eukaryote groups. In all four lineages, there is a significant increase in amino acid replacement rates when comparing: (i) disordered vs. ordered sites; (ii) random coil sites vs. sites in secondary structures; and (iii) inter-domain linker sites vs. sites in functional domains. Additionally, within Metazoans, Plants, and Saccharomycetes, there is a strong confounding interaction between intrinsic disorder and secondary structure—alignment sites exhibiting both high disorder propensity and involvement in secondary structures have very low average rates of sequence evolution. Analysis of gene ontology (GO) terms revealed that in all four lineages, a high fraction of sequences containing these conserved, disordered-structured sites are involved in nucleic acid binding. We also observe notable differences in the statistical trends of Alveolates, where intrinsically disordered sites are more variable than in other Eukaryotes and the statistical interactions between disorder and other factors are less pronounced.
Highlights
Nucleotide substitutions within protein-coding genes can produce downstream changes within the sequences of their translated expression products.protein molecular evolution entails the replacement of amino acid residues at various positions within a protein’s primary structure over time
Brown et al [8] found that proteins with long intrinsically disordered regions (IDRs) tend to experience higher overall levels of amino acid replacement than ordered proteins
22,395 (87%) of these clusters were suitable for downstream phylogenetic inference and site-wise evolutionary rate inference
Summary
Nucleotide substitutions within protein-coding genes can produce downstream changes (amino acid replacements) within the sequences of their translated expression products (proteins). Protein molecular evolution entails the replacement of amino acid residues at various positions (sites) within a protein’s primary structure (sequence) over time. The relative rates of amino acid replacement may vary significantly among sequence sites, and accounting for rate heterogeneity greatly increases the accuracy of phylogenetic reconstruction based on molecular evolutionary models [1]. This phenomenon has attracted considerable research examining the relationship between protein structure/function and site-specific rates of protein sequence evolution (see Echave et al [2] for a review). Brown et al [8] found that proteins with long intrinsically disordered regions (IDRs) tend to experience higher overall levels of amino acid replacement than ordered proteins
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