Mechanisms of protein evolution

Abstract

How do proteins evolve? How do changes in sequence mediate changes in protein structure, and in turn in function? This question has multiple angles, ranging from biochemistry and biophysics to evolutionary biology. This review provides a brief integrated view of some key mechanistic aspects of protein evolution. First, we explain how protein evolution is primarily driven by randomly acquired genetic mutations and selection for function, and how these mutations can even give rise to completely new folds. Then, we also comment on how phenotypic protein variability, including promiscuity, transcriptional and translational errors, may also accelerate this process, possibly via "plasticity-first" mechanisms. Finally, we highlight open questions in the field of protein evolution, with respect to the emergence of more sophisticated protein systems such as protein complexes, pathways, and the emergence of pre-LUCA enzymes.

Single-cell RNA sequencing analysis of shrimp immune cells identifies macrophage-like phagocytes

“…However, invertebrates have experienced a long evolution in a diversified environment, which has led to the fact that invertebrate immunity is extremely complex and immune cell typing in various invertebrates seems quite different ( Supplementary file 10 ). Fortunately, proteins seem to have evolved at a much slower rate ( Jayaraman et al, 2022 ), and cell-specific functional proteins are therefore the key to define cell subsets. Thus, in this study, we compared shrimp immune cell marker genes with their human homologs to identify evolutionary traces of innate immune cells between invertebrates and vertebrates ( Supplementary file 11 ).…”

Amino acid usage and tRNA expression underlies proteome adaptation inPlasmodium falciparum

“…A significant implication of our finding is the demonstration of a global selection sweep that affected the primary sequences of many proteins but may not necessarily impart a functional advantage. Although functional selection and neutral drift are believed to be the main drivers of protein evolution 54,55 , this study suggests that many non-functional missense mutations can be under positive selection for their regulatory effect, which are otherwise manifested as neural drift 55 . This adds new perspectives to the understanding of genome and protein evolution, such as on the thesis of adaptive mutation bias and on the frequent occurrence of low complexity regions in P. falciparum genome 2,46,54 .…”

“…Although functional selection and neutral drift are believed to be the main drivers of protein evolution 54,55 , this study suggests that many non-functional missense mutations can be under positive selection for their regulatory effect, which are otherwise manifested as neural drift 55 . This adds new perspectives to the understanding of genome and protein evolution, such as on the thesis of adaptive mutation bias and on the frequent occurrence of low complexity regions in P. falciparum genome 2,46,54 . This finding also draws attention to the limitation of studying translation dynamics by considering only codon usage bias, since in addition to codonidentity, AA-identity can also be a prominent factor evolved to influence translation.…”

Ancient loss of catalytic selenocysteine spurred convergent adaptation in a mammalian oxidoreductase

“…Mutations in these evolutionary constrained active sites typically reduce catalytic activity (Carter & Wells, 1988; Loeb et al, 1989; Rennell et al, 1991), a proxy for fitness in enzymes, and are consequently often deleterious. Still, when such mutations do occur and persist, they allow observation of mutational trajectories that either recover the rate of catalysis (Gromer et al, 2003) or open new protein functions (Jayaraman et al, 2022; Jensen, 1976). These trajectories, however, are limited by the enzyme’s sequence, as epistasis favours mutations whose interactions with other residues compensate for catalytic loss or advance alternative properties, with pleiotropy further limiting trajectories that improve one enzymatic property but compromise another (Storz, 2016; Weinreich et al, 2006).…”