  Molecular dynamics simulations were used to determine the binding affinities
between between the hormone 17 beta-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 beta isoforms, ER beta 1
and ER beta 2, and the recent whole genome duplication in the ancestral
salmonid created two ER alpha isoforms, ER alpha 1 and ER alpha 2. The
objective of our computational studies is to provide insight into the
underlying evolutionary pressures on these isoforms. For the ER alpha subtype
our results show that E2 binds preferentially to ER alpha 1 over ER alpha 2.
Tests of lineage specific dN/dS ratios indicate that the ligand binding domain
of the ER alpha 2 gene is evolving under relaxed selection relative to all
other ER alpha genes. Comparison with the highly conserved DNA binding domain
suggests that ER alpha 2 may be undergoing neofunctionalization possibly by
binding to another ligand. By contrast, both ER beta 1 and ER beta 2 bind
similarly to E2 and the best fitting model of selection indicates that the
ligand binding domain of all ER beta genes are evolving under the same level of
purifying selection, comparable to ER alpha 1.

Biological Physics;Computational Physics;Biomolecules