Patterns of evolution of host proteins involved in retroviral pathogenesis

Millan Ortiz,Raquel Martinez,Henrik Kaessmann,Amalio Telenti,Gabriela Bleiber

doi:10.1186/1742-4690-3-11

Abstract

BackgroundEvolutionary analysis may serve as a useful approach to identify and characterize host defense and viral proteins involved in genetic conflicts. We analyzed patterns of coding sequence evolution of genes with known (TRIM5α and APOBEC3G) or suspected (TRIM19/PML) roles in virus restriction, or in viral pathogenesis (PPIA, encoding Cyclophilin A), in the same set of human and non-human primate species.Results and conclusionThis analysis revealed previously unidentified clusters of positively selected sites in APOBEC3G and TRIM5α that may delineate new virus-interaction domains. In contrast, our evolutionary analyses suggest that PPIA is not under diversifying selection in primates, consistent with the interaction of Cyclophilin A being limited to the HIV-1M/SIVcpz lineage. The strong sequence conservation of the TRIM19/PML sequences among primates suggests that this gene does not play a role in antiretroviral defense.

Highlights

Evolutionary analysis may serve as a useful approach to identify and characterize host defense and viral proteins involved in genetic conflicts
Both genes were shown to have been shaped by positive selection, which led to the rapid fixation of adaptive amino acid replacement substitutions
To assess the potential of an evolutionary approach to identify further primate genes/proteins involved in virus defense, we analyzed coding sequence evolution of two additional genes, TRIM19 (PML) and PPIA, and reassessed the selective signatures of TRIM5α and APOBEC3G in a common set of primates, representing 40 million years of evolution [7]

Summary

Results and conclusion

This analysis revealed previously unidentified clusters of positively selected sites in APOBEC3G and TRIM5α that may delineate new virus-interaction domains. Our evolutionary analyses suggest that PPIA is not under diversifying selection in primates, consistent with the interaction of Cyclophilin A being limited to the HIV-1M/SIVcpz lineage. The strong sequence conservation of the TRIM19/PML sequences among primates suggests that this gene does not play a role in antiretroviral defense

Background

Yang Z

Goodman M

12. Yang Z

29. Telenti A