Evolutionary genetics is important for the understanding of HIV biology
Retroviruses have been intimately associated with the evolution of vertebrates. In many instances, they have effectively integrated in the host genome in a permanent fashion. Lentiviruses, a subgroup of the retroviruses that includes the human immunodeficiency virus HIV-1, infect numerous primate species in nature. The host, and in particularly humans, are expected to have built a dedicated system to assure effective defense and a peaceful coexistance with these ubiquitous infectious agents. It is reasonable to think that a species adaptation to retroviruses during history will modulate the response to modern retroviral infections - for example the response of humans to HIV-1. Indeed there are considerable differences in disease cause by lentiviruses across primate species, and across humans. The identification of the genetic differences underpinning inter- or intraspecies differences in susceptibility would greatly help the understanding of basic mechanisms of pathogenesis. This project will use tools of comparative genomics, and the complete genomes of 9 primates to understand the evolutionary characteristics of genes involved in pathogen response. In a second phase, the study will characterized the mutation burden in human genes involved in pathogen response by exploiting the data from 1000Genomes - the international project that aims at the detailed understanding of the structure and variation of the human genome. Lastly, the project will aim at the functional characterization of selected candidate genes and at the reconstruction of the ancestral states of host genes as well as of endogenous retroviruses integrated in the human genome. This work will generate a detailed annotation of the human genome in the context of evolution and of response to lentiviruses. Candidate genes will then be evaluate for a role in HIV-1 disease, and human variation in those genes will be assessed in their contribution to interindividual differences in susceptibility to infection and disease.