Computational Study of Evolutionary Selection Pressure on Rainbow Trout Estrogen Receptors

Molecular dynamics simulations were used to determine the binding affinities between the hormone 17[Image: see text]-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 ER[Image: see text] isoforms, ER[Image: see text] and ER[Image: see text], and the recent whole genome duplication in the ancestral salmonid created two ER[Image: see text] isoforms, ER[Image: see text] and ER[Image: see text]. The objective of our computational studies is to provide insight into the underlying evolutionary pressures on these isoforms. For the ER[Image: see text] subtype our results show that E2 binds preferentially to ER[Image: see text] over ER[Image: see text]. Tests of lineage specific [Image: see text]N/[Image: see text]S ratios indicate that the ligand binding domain of the ER[Image: see text] gene is evolving under relaxed selection relative to all other ER[Image: see text] genes. Comparison with the highly conserved DNA binding domain suggests that ER[Image: see text] may be undergoing neofunctionalization possibly by binding to another ligand. By contrast, both ER[Image: see text] and ER[Image: see text] bind similarly to E2 and the best fitting model of selection indicates that the ligand binding domain of all ER[Image: see text] genes are evolving under the same level of purifying selection, comparable to ER[Image: see text].