Evolutionary analysis of endogenous intronic retroviruses in primates reveals an enrichment in transcription binding sites associated with key regulatory processes.

Abstract

Endogenous retroviruses (ERVs) are the result of the integration of retroviruses into host DNA following germline infection. Endogenous retroviruses are made up of three main genes: gag, pol, and env, each of which encodes viral proteins that can be conserved or not. ERVs have been observed in a wide range of vertebrate genomes and their functions are associated with viral silencing and gene regulation. In this work, we studied the evolutionary history of endogenous retroviruses associated with five human genes (INPP5B, DET1, PSMA1, USH2A, and MACROD2), which are located within intron sections. To verify the retroviral origin of the candidates, several approaches were used to detect and locate ERV elements. Both orthologous and paralogous genes were identified by Ensembl and then analyzed for ERV presence using RetroTector. A phylogenetic tree was reconstructed to identify the minimum time point of ERV acquisition. From that search, we detected ERVs throughout the primate lineage and in some other groups. Also, we identified the minimum origin of the ERVs from the parvorder Catarrhini to the Homininae subfamily. With the data collected, and by observing the transcription factors annotated inside ERVs, we propose that these elements play a relevant role in gene expression regulation and they probably possess important features for tumorigenesis control.