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Comparative Study
. 2008 May;8(3):297-301.
doi: 10.1016/j.meegid.2008.01.004. Epub 2008 Jan 18.

Molecular evolution of the prostate cancer susceptibility locus RNASEL: evidence for positive selection

Kyle Summers  1 , Bernard Crespi
Affiliations
Comparative Study

Molecular evolution of the prostate cancer susceptibility locus RNASEL: evidence for positive selection

Kyle Summers et al. Infect Genet Evol. 2008 May.

Abstract

Recent research implicates viral infection as a factor that may contribute to the risk of prostate cancer. Allelic variation at the RNASEL locus is associated with the risk of infection by a newly discovered retrovirus called XMRV, and with hereditary risk of prostate cancer. This evidence suggests that the RNASEL locus has undergone antagonistic coevolution with the retrovirus over evolutionary time. If this is the case, then both the RNASEL locus and the retrovirus should show evidence of positive selection. Here we use molecular-evolutionary methods to investigate the prediction that the RNASEL locus will exhibit evidence of positive selection. We find evidence that positive selection has acted on this locus over evolutionary time. We further find, using a Bayesian estimation procedure, that Asp541Glu, which was found to be associated with prostate cancer risk in Caucasians in a recent meta-analysis, shows an elevated probability of positive selection. Previous studies provide evidence for rapid evolution of the infection-mediating gag gene in the XMRV retrovirus. Taken together, these results suggest that antagonistic coevolution may have occurred between a specific host locus involved in immune defense (RNASEL) and a viral pathogen. In turn, genetic variation associated with this apparent coevolution may influence susceptibility to prostate cancer.

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