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

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 approximately 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.

Trichoplax, the simplest known animal, contains an estrogen-related receptor but no estrogen receptor: Implications for estrogen receptor evolution

“…ERRs are still not fully understood [9,15,16,19,21] Trichoplax, which is considered to be the simplest metazoan [28,29] and of three lophotrochozoans: Capitella, a segmented worm, Helobdella, a leech and Lottia, a snail.…”

“…As a result, the ERR belongs to the orphan receptor group [5,6] in the nuclear receptor family of transcription factors [7][8][9][10].…”

Steroid metabolism in cnidarians: Insights from Nematostella vectensis

“…ER homologs have been identified in molluscs, but the mollusc ER does not bind estrogen and is constitutively active in cell-based assays (Keay et al, 2006). ERs have not been identified in the sequenced genomes of echinoderms, insects, nematodes, or N. vectensis (Bertrand et al, 2004;Enmark and Gustafsson, 2001;Goldstone et al, 2006;Howard-Ashby et al, 2006, Reitzel and Tarrant, submitted;Sluder et al, 1999); however, exogenous estrogens have been shown to affect reproduction in C. elegans and corals (Custodia et al, 2001;Tarrant et al, 2004). Thus, estrogens may bind to another nuclear receptor in these organisms or function through a different pathway.…”

The evolution of the ligand/receptor couple: A long road from comparative endocrinology to comparative genomics

“…This influence is well illustrated by a recent analysis of NR genes distribution and phylogeny in metazoans in which are compared the scenarios implied by the Ecdysozoan or Coelomata hypothesis on the evolutionary history of nuclear receptors (Bertrand et al, 2004). The use of alternative topologies of the metazoan tree (as the Coelomata hypothesis used for the analysis of the Forkhead family; Carlsson and Mahlapuu, 2002) may affect the conclusions drawn relative to the ancestry and evolution of specific genes.…”