Ligand binding was acquired during evolution of nuclear receptors

Abstract

We have characterized the adaptations of Helicobacter pylori to a rarely captured event in the evolution of its impact on host biology-the transition from chronic atrophic gastritis (ChAG) to gastric adenocarcinoma-and defined the impact of these adaptations on an intriguing but poorly characterized interaction between this bacterium and gastric epithelial stem cells. Bacterial isolates were obtained from a single human host colonized with a single dominant strain before and after his progression from ChAG to gastric adenocarcinoma during a 4-year interval. Draft genome assemblies were generated from two isolates, one ChAG-associated, the other cancer-associated. The cancer-associated strain was less fit in a gnotobiotic transgenic mouse model of human ChAG and better able to establish itself within a mouse gastric epithelial progenitorderived cell line (mGEP) that supports bacterial attachment. GeneChip-based comparisons of the transcriptomes of mGEPs and a control mouse gastric epithelial cell line revealed that, upon infection, the cancer-associated strain regulates expression of GEP-associated signaling and metabolic pathways, and tumor suppressor genes associated with development of gastric cancer in humans, in a manner distinct from the ChAG-associated isolate. The effects on GEP metabolic pathways, some of which were confirmed in gnotobiotic mice, together with observed changes in the bacterial transcriptome are predicted to support aspects of an endosymbiosis between this microbe and gastric stem cells. These results provide insights about how H. pylori may adapt to and influence stem cell biology and how its intracellular residency could contribute to gastric tumorigenesis. microbial pathogenesis ͉ intracellular bacteria ͉ genome sequencing ͉ functional genomics ͉ gnotobiotic mice

Co-evolution of steroidogenic and steroid-inactivating enzymes and adrenal and sex steroid receptors

“…Thus far, adrenal and sex steroid receptors have been found only in vertebrates (Baker, 2002a(Baker, , 2003. This is consistent with PCR analysis of DNA from phylogenetically diverse animals (Escriva et al 1997) and sequence analysis steroid receptors (Baker, 1997(Baker, , 2001b(Baker, , 2003Escriva et al, 2000), both of which conclude that adrenal and sex steroid receptors arose at the beginning of the vertebrate line.…”

“…Phylogenetic analysis of the adrenal and sex steroid receptors indicates that they arose by a series of gene duplications (Baker, 1997(Baker, , 2001b(Baker, , 2002bEscriva et al, 1997Escriva et al, , 2000Thornton, 2001). Analysis of the evolution of the ligand-binding domain indicates that the ER is the most ancient of the adrenal and sex steroid receptors (Baker, 2001b(Baker, , 2002bThornton 2001).…”

Molecular phylogeny of the ETS gene family

“…This contrasts with the pattern observed for Hox/HOM or nuclear receptor genes for which a clear increase in gene number from diploblastic grade animals to triploblastic coelomates has been observed, as exampli®ed for the Hox gene complex of nematodes containing only ®ve genes whereas the complex of Drosophila contains eight genes and the archetypal vertebrate complex 13 genes (reviewed in Averof, 1997). For nuclear receptors, it has been proposed that only two of the six described subfamilies were present in diploblastic Metazoans (Escriva et al, 1997;Laudet, 1997). The conservation in gene number for ETS family implies that each group of ETS genes should be found in each studied Metazoan.…”

Evolution of adrenal and sex steroid action in vertebrates: a ligand‐based mechanism for complexity

“…1) [5][6][7][8], which is a ligand-based based mechanism for regulating the interactions between networks of transcription factors [9][10][11], as well as directly regulating the transcription of specific genes. Receptors for these steroids have not been found in invertebrates.…”