Evolutionary Genomics of Nuclear Receptors: From Twenty-Five Ancestral Genes to Derived Endocrine Systems

TLDR

Bilaterian animals possess complex endocrine systems regulated by nuclear receptors—transcription factors for steroids, retinoids, and other hormones—that share a common protein organization. The study aims to chart bilaterian nuclear hormone receptor evolution by characterizing all nuclear receptor genes in nine animal genomes and using phylogenetic analysis to date the events from an ancestral gene to current diversity. The authors identified nuclear receptor genes in nine animal genomes and searched expressed sequence tags from key lineages lacking genomes, then performed phylogenetic analysis. They found approximately 25 nuclear receptor genes in Urbilateria, with differential gene loss and duplication shaping lineage-specific repertoires, and that major receptors such as steroid and thyroid hormone receptors were already present in Urbilateria.

Abstract

Bilaterian animals are notably characterized by complex endocrine systems. The receptors for many steroids, retinoids, and other hormones belong to the superfamily of nuclear receptors, which are transcription factors regulating many aspects of development and homeostasis. Despite a diversity of regulatory mechanisms and physiological roles, nuclear receptors share a common protein organization. To obtain the broad picture of bilaterian nuclear hormone receptor evolution, we have characterized the complete set of nuclear receptor genes from nine animal genome sequences and analyzed it in a phylogenetic framework. In addition, expressed sequence tags from key lineages with no available genome sequence were also searched. This allows us to date the evolutionary events that led from an ancestral nuclear receptor gene, in an early metazoan, to present day diversity. We show that there were ∼25 nuclear receptor genes in Urbilateria, the ancestor of bilaterians, at which point the fundamental diversity of the subfamily was already established. Surprisingly, differential gene loss played an important role in the evolution of different nuclear receptor sets in bilaterian lineages. The nuclear receptor distribution was also shaped by periods of gene duplication, essentially in vertebrates, as well as a lineage-specific duplication burst in nematodes. Our results imply that the genes for major receptors such as steroid receptors or thyroid hormone receptors were present in Urbilateria.