Phylogeny of vertebrate nuclear receptors--analysis of variance components in protein sequences.

Nuclear receptors (NR) constitute a large family of proteins and play a crucial role in regulating mineral metabolism and physiological homeostasis of various organ systems. The aim of this study was to elucidate whether the variance among NRs of estrogen, androgen and vitamin-D in various vertebrate species including humans is attributed to differences between the taxonomic groups within a specific receptor (i.e. between orthologous) or between the different proteins within the taxon (i.e. between paralogous genes). Published data on 57 protein sequences of the above NRs were used for phylogenetic analysis. The results showed that in DNA- and ligand-binding regions, 94% and 70% of variance is due to differences between the three proteins. However, in non-binding regions, 47% of the variance results from differences between the three paralogous proteins. Human sequences consistently clustered with their mammal orthologous within the three groups of NR sequences, clearly indicating that evolution of human sequences is not distinct from mammal sequence evolution.