10.5061/DRYAD.BG3G3
Baker, Jennifer L.
George Washington University
Dunn, Katherine A.
Dalhousie University
Mingrone, Joseph
Dalhousie University
Wood, Bernard A.
George Washington University
Karpinski, Beverly A.
George Washington University
Sherwood, Chet C.
George Washington University
Wildman, Derek E.
Maynard, Thomas M.
George Washington University
Bielawski, Joseph P.
Dalhousie University
Data from: Functional divergence of the nuclear receptor NR2C1 as a
modulator of pluripotentiality during hominid evolution
Dryad
dataset
2017
testicular receptor 2 (TR2) pluripotentiality
hominid evolutionary survey
Nr2c1
ancestral gene reconstruction (AGR)
testicular receptor 2 (TR2)
Codon models
2017-01-06T15:32:29Z
2017-01-06T15:32:29Z
en
https://doi.org/10.1534/genetics.115.183889
227925 bytes
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CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
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.
NR alignmentsNR
alignmentspaml_files_for_dryad.zipStructural_partitionsStructural_partitions4cat_structural_partitions.zip