Fedonin, G. | Search bioRxiv

bioRxiv2022

Evidence for coordinated evolution at amino acid sites of SARS-CoV-2 spike

It is currently unclear why SARS-Cov-2 has adapted in a stepwise manner, with multiple beneficial mutations accumulating in a rapid succession at the origins of VOCs. Here, we searched for coordinated evolution of amino acid sites in the spike protein of SARS-Cov-2. We searched for concordantly evolving site pairs (CSP) for which changes at one site were rapidly followed by changes at the other site in the same lineage. We detected 46 sites which formed 45 CSP. Sites in CSP were closer to each other in the protein structure than random pairs, indicating that concordant evolution has a functional basis. Notably, site pairs carrying lineage defining mutations of the four VOCs that circulated before May 2021 are enriched in CSP, indicating that the origin of these VOCs could have been facilitated by positive epistasis. Additionally, we detected four discordantly evolving pairs of sites where mutations at one site unexpectedly rarely occurred on the background of a specific allele at another site, namely on the wild-type D at site 614 (for two pairs) or at derived Y in the site 501 (for two other pairs). Our findings hint that positive epistasis between accumulating mutations could have delayed the assembly of advantageous combinations of mutations comprising at least some of the VOCs.

evolutionary biology↗

bioRxiv2020

Episodic evolution of coadapted sets of amino acid sites in mitochondrial proteins

The rate of evolution differs between protein sites and changes with time. However, the link between these two phenomena remains poorly understood. Here, we design a phylogenetic approach for distinguishing pairs of amino acid sites that undergo coordinated evolution, i.e., such that substitutions at one site trigger subsequent substitutions at the other; and also pairs of sites that undergo discordant evolution, so that substitutions at one site impede subsequent substitutions at the other. We distinguish groups of amino acid sites that undergo coordinated evolution and evolve discordantly from other such groups. In mitochondrially encoded proteins of metazoans and fungi, we show that concordantly evolving sites are clustered in protein structures. Moreover, the substitution rates within individual concordant groups themselves change in the course of evolution, and phylogenetic positions of these changes are consistent between proteins, suggesting common selective forces underlying them. Author summaryEvolution in most protein sites is constrained by alleles in other sites, this phenomena is called epistasis. Generally, newly arisen allele, if it would not be lost, increases its fitness with time due to adaptive mutations occurred in other sites in the process called the entrenchment. Thus, we expect that the evolution of sites would be coordinated, such that mutations in sites rapidly follow each other on phylogenetic lineages. Indeed, we have observed such coordinated evolution of sites in five proteins encoded in the mitochondria genomes of metazoan and fungi. Unexpectedly, coordinated evolution is observed only for nearby sites on protein structures, such that each protein could be partitioned into several groups of concordantly evolving sites. Evolution of sites from different groups is discordant, i.e. their mutations repel each other into different phylogenetic lineages or clades. Thus, the proteins encoded in mitochondrial genome consist of the sort of structural blocks like elements of the LEGO kit. Some of them have functional specialization, e.g. some blocks are associated with interfaces between proteins composing respiratory complexes.

evolutionary biology↗