Extensive intraspecies cryptic variation in an ancient embryonic gene regulatory network.

TitleExtensive intraspecies cryptic variation in an ancient embryonic gene regulatory network.
Publication TypeJournal Article
Year of Publication2019
AuthorsCleuren YNTorres, Ewe CKiang, Chipman KC, Mears ER, Wood CG, Al-Alami CEmma Alma, Alcorn MR, Turner TL, Joshi PM, Snell RG, Rothman JH
Date Published2019 08 15
KeywordsAnimals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, DNA-Binding Proteins, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Genetic Variation, Intracellular Signaling Peptides and Proteins, Progranulins, Transcription Factors, Wnt Proteins

Innovations in metazoan development arise from evolutionary modification of gene regulatory networks (GRNs). We report widespread cryptic variation in the requirement for two key regulatory inputs, SKN-1/Nrf2 and MOM-2/Wnt, into the endoderm GRN. While some natural isolates show a nearly absolute requirement for these two regulators, in others, most embryos differentiate endoderm in their absence. GWAS and analysis of recombinant inbred lines reveal multiple genetic regions underlying this broad phenotypic variation. We observe a reciprocal trend, in which genomic variants, or knockdown of endoderm regulatory genes, that result in a high SKN-1 requirement often show low MOM-2/Wnt requirement and suggesting that cryptic variation in the endoderm GRN may be tuned by opposing requirements for these two key regulatory inputs. These findings reveal that while the downstream components in the endoderm GRN are common across metazoan phylogeny, initiating regulatory inputs are remarkably plastic even within a single species.

Alternate JournalElife
PubMed ID31414984
PubMed Central IDPMC6754231
Grant List1R01HD082347 / NH / NIH HHS / United States
1R01HD081266 / NH / NIH HHS / United States
P40 OD010440 / OD / NIH HHS / United States
R01 HD081266 / HD / NICHD NIH HHS / United States
R01 HD082347 / HD / NICHD NIH HHS / United States