Cryptic genetic variation in a heat shock protein modifies the outcome of a mutation affecting epidermal stem cell development in C. elegans

A fundamental question in medical genetics is how the genetic background modifies the phenotypic outcome of mutations. We address this question by focusing on the seam cells, which display stem cell properties in the epidermis of Caenorhabditis elegans . We demonstrate that a putative null mutation...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications 2021-05, Vol.12 (1), p.3263-3263, Article 3263
Main Authors: Koneru, Sneha L., Hintze, Mark, Katsanos, Dimitris, Barkoulas, Michalis
Format: Article
Language:English
Subjects:
14
14/63
38
38/32
42/89
45
631/208/135
631/208/2490
631/208/480
Amino acids
Caenorhabditis elegans
Cell fate
Deletion
Epidermis
Gene mapping
Genetic diversity
Genetics
Genotype & phenotype
Heat shock proteins
Humanities and Social Sciences
multidisciplinary
Mutation
Nematodes
Phenotypes
Quantitative trait loci
Science
Science (multidisciplinary)
Signaling
Stem cells
Transcription factors
Wnt protein
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A fundamental question in medical genetics is how the genetic background modifies the phenotypic outcome of mutations. We address this question by focusing on the seam cells, which display stem cell properties in the epidermis of Caenorhabditis elegans . We demonstrate that a putative null mutation in the GATA transcription factor egl-18 , which is involved in seam cell fate maintenance, is more tolerated in the CB4856 isolate from Hawaii than the lab reference strain N2 from Bristol. We identify multiple quantitative trait loci (QTLs) underlying the difference in phenotype expressivity between the two isolates. These QTLs reveal cryptic genetic variation that reinforces seam cell fate through potentiating Wnt signalling. Within one QTL region, a single amino acid deletion in the heat shock protein HSP-110 in CB4856 is sufficient to modify Wnt signalling and seam cell development, highlighting that natural variation in conserved heat shock proteins can shape phenotype expressivity. How the genetic background modifies the expression of mutations is a key question that is addressed in this study in the context of seam cell development in Caenorhabditis elegans isolates. One amino acid deletion in a conserved heat shock protein is sufficient to shape phenotype expressivity upon mutation of a GATA transcription factor.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-23567-1