Extensive intraspecies cryptic variation in an ancient embryonic gene regulatory network
| Autor: | Pradeep M. Joshi, Emily R Mears, Cricket G. Wood, Thomas L. Turner, Kyle C. Chipman, Russell G. Snell, Yamila N. Torres Cleuren, Coco Emma Alma Al-Alami, Melissa R. Alcorn, Chee Kiang Ewe, Joel H. Rothman |
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| Rok vydání: | 2019 |
| Předmět: |
Gene regulatory network
Genome-wide association study Disease Progranulins 0302 clinical medicine GWAS Gene Regulatory Networks Biology (General) Caenorhabditis elegans Regulator gene 0303 health sciences General Neuroscience genotype-by-sequencing Intracellular Signaling Peptides and Proteins Wnt signaling pathway Gene Expression Regulation Developmental General Medicine Phenotype DNA-Binding Proteins medicine.anatomical_structure embryonic structures C. elegans Medicine Endoderm GRN Research Article animal structures QH301-705.5 Science Genomics Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences SKN-1 Phylogenetics medicine Animals cryptic variation Caenorhabditis elegans Proteins Gene development 030304 developmental biology General Immunology and Microbiology Genetic Variation Genetics and Genomics biology.organism_classification Embryonic stem cell Wnt Proteins Evolutionary biology Developmental biology 030217 neurology & neurosurgery Developmental Biology Transcription Factors |
| Zdroj: | eLife eLife, Vol 8 (2019) eLIFE |
| DOI: | 10.1101/628495 |
| Popis: | 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 C. elegans 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 vice-versa, 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. eLife digest Two people with the same disease, or who inherit the same genetic mutation, often show different symptoms or respond to medical treatments in different ways. This is because many traits are not the result of a single gene, but of several genes interacting with each other in complex ways to form networks that lead to many possible outcomes. Gene regulatory networks, which control how animals develop, change over evolutionary time to create the vast variety of different species that exist today. However, it is still unclear how mutations in these networks can occur without negatively impacting their activity, or how networks become rewired during evolution. To address these questions, Torres Cleuren et al. studied the gene regulatory network that controls the development of the gut across approximately 100 different strains of Caenorhabditis elegans, a widely studied nematode worm. This involved testing how switching off particular genes affected gut development in embryos of the worm. The experiments revealed that the first steps in the gene regulatory networks that control gut development vary drastically between the different wild strains of C. elegans. For example, in some of the strains, two genes known as skn-1 and mom-2 are essential for gut formation, whereas in others the gut often forms even when these genes are switched off. These results support the idea that some of the genes in the network can compensate for loss of others, explaining how mutations can accumulate without impacting the development of the embryo. The findings of Torres Cleuren et al. provide important insights into how gene regulatory networks can be rewired, with some components accumulating mutations and acquiring new roles, while others stay the same. |
| Databáze: | OpenAIRE |
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