Abstract
Viruses interact with hundreds to thousands of proteins in mammals, yet adaptation against viruses has only been studied in a few proteins specialized in antiviral defense. Whether adaptation to viruses typically involves only specialized antiviral proteins or affects a broad array of virus-interacting proteins is unknown. Here, we analyze adaptation in ~1300 virus-interacting proteins manually curated from a set of 9900 proteins conserved in all sequenced mammalian genomes. We show that viruses (i) use the more evolutionarily constrained proteins within the cellular functions they interact with and that (ii) despite this high constraint, virus-interacting proteins account for a high proportion of all protein adaptation in humans and other mammals. Adaptation is elevated in virus-interacting proteins across all functional categories, including both immune and non-immune functions. We conservatively estimate that viruses have driven close to 30% of all adaptive amino acid changes in the part of the human proteome conserved within mammals. Our results suggest that viruses are one of the most dominant drivers of evolutionary change across mammalian and human proteomes.
Highlights
We excluded interactions identified by high-throughput experiments because we were concerned about a high rate of false positives (Mellacheruvu et al, 2013)
We further investigate the excess of adaptation for the specific VIPs of ten human viruses and in the 20 high level Gene Ontology (GO) categories with the most VIPs (Figure 4A and B)
In line with the McDonald-Kreitman test (MK test), we find that the excess of adaptation in mammals is robust to the potential confounding factors of expression at the RNA and protein levels, and to the number of host protein-protein interactions (Supplementary file 1H)
Summary
A number of proteins with a specialized role in antiviral defense have been shown to have exceptionally high rates of adaptation (Cagliani et al, 2011; Cagliani et al, 2012; Elde et al, 2009; Fumagalli et al, 2010; Kerns et al, 2008; Liu et al, 2005; Sawyer et al, 2004; Sawyer et al, 2005; Sawyer et al, 2007; Sironi et al, 2012; Vasseur et al, 2011). Very few cases of adaptation to viruses are known outside of fast evolving, specialized antiviral proteins Computational and systems biology Genomics and evolutionary biology eLife digest When an environmental change occurs, species are able to adapt in response due to mutations in their DNA. These mutations occur randomly, by chance some of them make the organism better suited to their new environment. Using our approach we reach an amino-acid level understanding of parallel adaptive evolution in aminopeptidase N in response to coronaviruses in a wide range of mammals
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