Evolutionary rate shifts suggest species-specific adaptation events in HIV-1 and SIV

Maoz Gelbart; Adi Stern

Our results indeed suggest an evolutionary rate shift event in Gag30 yet are not 209 conclusive about the branches in which the rate shift happened. This is likely since this site 210 displays a "content shift" rather than a strong "rate shift" (elaborated in the discussion). 211 Understanding the molecular changes in a pathogen when adapting to infect a new host species 214 is of high importance. To the best of our knowledge, our study represents the first large-scale 215 approach to detect adaptation events in the transition from non-human primates to humans, 216 and relies on a robust phylogenetic modeling approach. We discovered many lineage-specific 217 adaptation-like events in many proteins of HIV-1, SIVgor and SIVcpzpts, and have reported sites 218 in where groups M and O suggested to undergone parallel rate shifts. The majority of sites 219 . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/190769 doi: bioRxiv preprint undergoing rate deceleration were found in the Env protein; when correcting for protein size, 220 the relatively highest number of rate decelerating were found in proteins that adapted to host 221 restriction factors. Accordingly, we suggest that the major common barrier for a host species 222 jump is composed of both the entry stage and the stage where the virus must overcome the first 223 barrier of cellular defenses. Our results further support a differential model of adaptation: 224 groups M and O underwent adaptation in different proteins, and when adaptation occurred at 225 similar sites, the amino-acid was different in both groups. This model is supported by the fact 226 that activity of group M and O proteins are indeed different (e.g., Vpu), and by the fact that each 227 group originated from an SIV from a different primate. 228