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The genetics of gene expression in a Caenorhabditis elegans multiparental recombinant inbred line population.

ABSTRACT: Studying genetic variation of gene expression provides a powerful way to unravel the molecular components underlying complex traits. Expression quantitative trait locus (eQTL) studies have been performed in several different model species, yet most of these linkage studies have been based on the genetic segregation of two parental alleles. Recently, we developed a multiparental segregating population of 200 recombinant inbred lines (mpRILs) derived from four wild isolates (JU1511, JU1926, JU1931, and JU1941) in the nematode Caenorhabditis elegans. We used RNA-seq to investigate how multiple alleles affect gene expression in these mpRILs. We found 1789 genes differentially expressed between the parental lines. Transgression, expression beyond any of the parental lines in the mpRILs, was found for 7896 genes. For expression QTL mapping almost 9000 SNPs were available. By combining these SNPs and the RNA-seq profiles of the mpRILs, we detected almost 6800 eQTLs. Most trans-eQTLs (63%) co-locate in six newly identified trans-bands. The trans-eQTLs found in previous two-parental allele eQTL experiments and this study showed some overlap (17.5-46.8%), highlighting on the one hand that a large group of genes is affected by polymorphic regulators across populations and conditions, on the other hand, it shows that the mpRIL population allows identification of novel gene expression regulatory loci. Taken together, the analysis of our mpRIL population provides a more refined insight into C. elegans complex trait genetics and eQTLs in general, as well as a starting point to further test and develop advanced statistical models for detection of multiallelic eQTLs and systems genetics studying the genotype-phenotype relationship.

SUBMITTER: Snoek BL

PROVIDER: S-EPMC8496280 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe nematode Caenorhabditis elegans has been extensively used to explore the relationships between complex traits, genotypes, and environments. Complex traits can vary across different genotypes of a species, and the genetic regulators of trait variation can be mapped on the genome using quantitative trait locus (QTL) analysis of recombinant inbred lines (RILs) derived from genetically and phenotypically divergent parents. Most RILs have been derived from crossing two parents from globally distant locations. However, the genetic diversity between local C. elegans populations can be as diverse as between global populations and could thus provide means of identifying genetic variation associated with complex traits relevant on a broader scale.ResultsTo investigate the effect of local genetic variation on heritable traits, we developed a new RIL population derived from 4 parental wild isolates collected from 2 closely located sites in France: Orsay and Santeuil. We crossed these 4 genetically diverse parental isolates to generate a population of 200 multi-parental RILs and used RNA-seq to obtain sequence polymorphisms identifying almost 9000 SNPs variable between the 4 genotypes with an average spacing of 11 kb, doubling the mapping resolution relative to currently available RIL panels for many loci. The SNPs were used to construct a genetic map to facilitate QTL analysis. We measured life history traits such as lifespan, stress resistance, developmental speed, and population growth in different environments, and found substantial variation for most traits. We detected multiple QTLs for most traits, including novel QTLs not found in previous QTL analysis, including those for lifespan and pathogen responses. This shows that recombining genetic variation across C. elegans populations that are in geographical close proximity provides ample variation for QTL mapping.ConclusionTaken together, we show that using more parents than the classical two parental genotypes to construct a RIL population facilitates the detection of QTLs and that the use of wild isolates facilitates the detection of QTLs. The use of multi-parent RIL populations can further enhance our understanding of local adaptation and life history trade-offs.

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The genetics of gene expression in a Caenorhabditis elegans multiparental recombinant inbred line population.

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