Functional Divergence of the Nuclear Receptor NR2C1 As a Modulator of Pluripotentiality During Hominid Evolution

Overview

Journal Genetics

Publisher Oxford University Press

Specialty Genetics

Date 2016 Apr 15

PMID 27075724

Citations 11

Authors

Jennifer L Baker

Katherine A Dunn

Joseph Mingrone

Bernard A Wood

Beverly A Karpinski

Chet C Sherwood

Derek E Wildman

Thomas M Maynard

Joseph P Bielawski

Affiliations

Soon will be listed here.

Abstract

Genes encoding nuclear receptors (NRs) are attractive as candidates for investigating the evolution of gene regulation because they (1) have a direct effect on gene expression and (2) modulate many cellular processes that underlie development. We employed a three-phase investigation linking NR molecular evolution among primates with direct experimental assessment of NR function. Phase 1 was an analysis of NR domain evolution and the results were used to guide the design of phase 2, a codon-model-based survey for alterations of natural selection within the hominids. By using a series of reliability and robustness analyses we selected a single gene, NR2C1, as the best candidate for experimental assessment. We carried out assays to determine whether changes between the ancestral and extant NR2C1s could have impacted stem cell pluripotency (phase 3). We evaluated human, chimpanzee, and ancestral NR2C1 for transcriptional modulation of Oct4 and Nanog (key regulators of pluripotency and cell lineage commitment), promoter activity for Pepck (a proxy for differentiation in numerous cell types), and average size of embryological stem cell colonies (a proxy for the self-renewal capacity of pluripotent cells). Results supported the signal for alteration of natural selection identified in phase 2. We suggest that adaptive evolution of gene regulation has impacted several aspects of pluripotentiality within primates. Our study illustrates that the combination of targeted evolutionary surveys and experimental analysis is an effective strategy for investigating the evolution of gene regulation with respect to developmental phenotypes.

Citing Articles

Cadmium activation of wild-type and constitutively active estrogen receptor alpha.

Psaltis J, Wang Q, Yan G, Gahtani R, Huang N, Haddad B Front Endocrinol (Lausanne). 2024; 15:1380047.

PMID: 39184142 PMC: 11341946. DOI: 10.3389/fendo.2024.1380047.

Diversity and Evolution of Frog Visual Opsins: Spectral Tuning and Adaptation to Distinct Light Environments.

Schott R, Fujita M, Streicher J, Gower D, Thomas K, Loew E Mol Biol Evol. 2024; 41(4).

PMID: 38573520 PMC: 10994157. DOI: 10.1093/molbev/msae049.

Adaptive Evolution of the OAS Gene Family Provides New Insights into the Antiviral Ability of Laurasiatherian Mammals.

Liu G, Wu X, Shang Y, Wang X, Zhou S, Zhang H Animals (Basel). 2023; 13(2).

PMID: 36670749 PMC: 9854896. DOI: 10.3390/ani13020209.

Genomic evidence of adaptive evolution in the reptilian SOCS gene family.

Xia T, Zhang L, Sun G, Yang X, Zhang H PeerJ. 2021; 9:e11677.

PMID: 34221740 PMC: 8236234. DOI: 10.7717/peerj.11677.

Contrast-FEL-A Test for Differences in Selective Pressures at Individual Sites among Clades and Sets of Branches.

Kosakovsky Pond S, Wisotsky S, Escalante A, Magalis B, Weaver S Mol Biol Evol. 2020; 38(3):1184-1198.

PMID: 33064823 PMC: 7947784. DOI: 10.1093/molbev/msaa263.

References

Gruppuso P, Bienieki T, FARIS R . The relationship between differentiation and proliferation in late gestation fetal rat hepatocytes. Pediatr Res. 1999; 46(1):14-9. DOI: 10.1203/00006450-199907000-00003. View

Niwa H, Miyazaki J, Smith A . Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet. 2000; 24(4):372-6. DOI: 10.1038/74199. View

Wasserman W, Palumbo M, Thompson W, Fickett J, Lawrence C . Human-mouse genome comparisons to locate regulatory sites. Nat Genet. 2000; 26(2):225-8. DOI: 10.1038/79965. View

Bourguet W, Germain P, Gronemeyer H . Nuclear receptor ligand-binding domains: three-dimensional structures, molecular interactions and pharmacological implications. Trends Pharmacol Sci. 2000; 21(10):381-8. DOI: 10.1016/s0165-6147(00)01548-0. View

Mcbrearty S, Brooks A . The revolution that wasn't: a new interpretation of the origin of modern human behavior. J Hum Evol. 2000; 39(5):453-563. DOI: 10.1006/jhev.2000.0435. View

Whelan S, Goldman N . A general empirical model of protein evolution derived from multiple protein families using a maximum-likelihood approach. Mol Biol Evol. 2001; 18(5):691-9. DOI: 10.1093/oxfordjournals.molbev.a003851. View

Thornton J . Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions. Proc Natl Acad Sci U S A. 2001; 98(10):5671-6. PMC: 33271. DOI: 10.1073/pnas.091553298. View

Robinson-Rechavi M, Carpentier A, Duffraisse M, Laudet V . How many nuclear hormone receptors are there in the human genome?. Trends Genet. 2001; 17(10):554-6. DOI: 10.1016/s0168-9525(01)02417-9. View

Yang Z, Swanson W . Codon-substitution models to detect adaptive evolution that account for heterogeneous selective pressures among site classes. Mol Biol Evol. 2001; 19(1):49-57. DOI: 10.1093/oxfordjournals.molbev.a003981. View

10.

Boiani M, Eckardt S, Scholer H, McLaughlin K . Oct4 distribution and level in mouse clones: consequences for pluripotency. Genes Dev. 2002; 16(10):1209-19. PMC: 186284. DOI: 10.1101/gad.966002. View

11.

Yang Z, Nielsen R . Codon-substitution models for detecting molecular adaptation at individual sites along specific lineages. Mol Biol Evol. 2002; 19(6):908-17. DOI: 10.1093/oxfordjournals.molbev.a004148. View

12.

Kent W, Sugnet C, Furey T, Roskin K, Pringle T, Zahler A . The human genome browser at UCSC. Genome Res. 2002; 12(6):996-1006. PMC: 186604. DOI: 10.1101/gr.229102. View

13.

Hu Y, Shyr C, Che W, Mu X, Kim E, Chang C . Suppression of estrogen receptor-mediated transcription and cell growth by interaction with TR2 orphan receptor. J Biol Chem. 2002; 277(37):33571-9. DOI: 10.1074/jbc.M203531200. View

14.

Katoh K, Misawa K, Kuma K, Miyata T . MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Res. 2002; 30(14):3059-66. PMC: 135756. DOI: 10.1093/nar/gkf436. View

15.

Chang B, Jonsson K, Kazmi M, Donoghue M, Sakmar T . Recreating a functional ancestral archosaur visual pigment. Mol Biol Evol. 2002; 19(9):1483-9. DOI: 10.1093/oxfordjournals.molbev.a004211. View

16.

Lee Y, Lee H, Chang C . Recent advances in the TR2 and TR4 orphan receptors of the nuclear receptor superfamily. J Steroid Biochem Mol Biol. 2002; 81(4-5):291-308. DOI: 10.1016/s0960-0760(02)00118-8. View

17.

Forsberg R, Christiansen F . A codon-based model of host-specific selection in parasites, with an application to the influenza A virus. Mol Biol Evol. 2003; 20(8):1252-9. DOI: 10.1093/molbev/msg149. View

18.

Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K . The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. 2003; 113(5):631-42. DOI: 10.1016/s0092-8674(03)00393-3. View

19.

Anisimova M, Nielsen R, Yang Z . Effect of recombination on the accuracy of the likelihood method for detecting positive selection at amino acid sites. Genetics. 2003; 164(3):1229-36. PMC: 1462615. DOI: 10.1093/genetics/164.3.1229. View

20.

Gaucher E, Thomson J, Burgan M, Benner S . Inferring the palaeoenvironment of ancient bacteria on the basis of resurrected proteins. Nature. 2003; 425(6955):285-8. DOI: 10.1038/nature01977. View