Computational study of evolutionary selection pressure on rainbow trout estrogen receptors

Abstract

Molecular dynamics simulations were used to determine the binding affinities between the hormone 17β-estradiol (E2) and different estrogen receptor (ER) isoforms in the rainbow trout, Oncorhynchus mykiss. Previous phylogenetic analysis indicates that a whole genome duplication prior to the divergence of ray-finned fish led to two distinct ERβ isoforms, ERβ1 and ERβ2, and the recent whole genome duplication in the ancestral salmonid created two ERα isoforms, ERα1 and ERα2. The objective of our computational studies is to provide insight into the underlying evolutionary pressures on these isoforms. For the ERα subtype our results show that E2 binds preferentially to ERα1 over ERα2. Tests of lineage specific dN/dS ratios indicate that the ligand binding domain of the ERα2 gene is evolving under relaxed selection relative to all other ERα genes. Comparison with the highly conserved DNA binding domain suggests that ERα2 may be undergoing neofunctionalization possibly by binding to another ligand. By contrast, both ERβ1 and ERβ2 bind similarly to E2 and the best fitting model of selection indicates that the ligand binding domain of all ERβ genes are evolving under the same level of purifying selection, comparable to ERα1. © 2010 Shyu et al.