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

Maoz Gelbart; Adi Stern

We have previously developed the RASER tool to identify sites that display change in the rate of 63 evolution along a given branch of a phylogenetic tree (see example in Figure 1) to rate deceleration events, as they likely indicate a gain of function in a protein. In Figure 2 we 87 mapped the percent of rate shifts in each protein observed in each lineage, corresponding to 88 different virus speciation events. While rate deceleration distribution patterns differed between 89 the different lineages (see Figure 2 and Supplementary Table 1), one common theme was that 90 all prominent branches underwent a significant portion of their rate deceleration events in the 91 Env protein. The next two common rate decelerating proteins were Gag and Pol identified in all 92 four highlighted branches, which is expected given that together with Env these are the longest 93 proteins in HIV/SIV. When controlling for protein size (as in Table 1 ), a different pattern 94 emerged: Vpu seems to have undergone a disproportionate portion of rate deceleration events, 95 in particular in the branch leading to group M. In general, the rate deceleration patterns for the 96 non-structural proteins seemed to be branch-specific: In the branch leading to SIVgor and group 97 The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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 groups M and O. This may indicate a relaxation of prior constraint as the SIV allele was 120 maintained in many HIV-1 sequences. 121 research into the origins of the HIV-1 pandemic and its sources identified several major 126 adaptation events of HIV-1 to its human host. These events include adapting to cellular 127 variations such as differences in host receptor CD4; overcoming host innate immune restriction 128 factors such as Tetherin (BST-2) and APOBEC3G; and of course, evasion from the adaptive 129 immune system [16, [20] [21] [22] [23] [24] [25] . We therefore sought to evaluate whether the proposed rate shifts 130 agree with the known adaptation events. 131