A multi-parent recombinant inbred line population ofCaenorhabditis elegansenhances mapping resolution and identification of novel QTLs for complex life-history traits

Abstract

25 Local populations of the bacterivorous nematode Caenorhabditis elegans can be genetically 26 almost as diverse as global populations. To investigate the effect of local genetic variation on 27 heritable traits, we developed a new recombinant inbred line (RIL) population derived from 28 four wild isolates. The wild isolates were collected from two closely located sites in France: 29 Orsay and Santeuil. By crossing these four genetically diverse parental isolates a population 30 of 200 RILs was constructed. RNA-seq was used to obtain sequence polymorphisms 31 identifying almost 9000 SNPs variable between the four genotypes with an average spacing 32 of 11 kb, possibly doubling the mapping resolution relative to currently available RIL panels. 33The SNPs were used to construct a genetic map to facilitate QTL analysis. Life history traits, 34 such as lifespan, stress resistance, developmental speed and population growth were 35 measured in different environments. For most traits substantial variation was found, and 36 multiple QTLs could be detected, including novel QTLs not found in previous QTL analysis, 37 for example for lifespan or pathogen responses. This shows that recombining genetic 38 variation across C. elegans populations that are in geographical close proximity provides 39 ample variation for QTL mapping. Taken together, we show that RNA-seq can be used for 40 genotyping, that using more parents than the classical two parental genotypes to construct a 41 RIL population facilitates the detection of QTLs and that the use of wild isolates permits 42 analysis of local adaptation and life history trade-offs.43 44Determining how genotype-phenotype relationships are controlled is at the heart of genetics. 45Understanding how the relationships between traits, genotypes and environments are controlled is 46 also crucial for traits relevant to the evolved context of the species [1, 2]. The identification and 47 characterization of allelic variants associated with complex traits has been a major challenge in 48 plant and animal breeding as well as disease genetics. Many complex traits vary in a continuous 49 way across different genotypes of a species. It is this phenotypic variation that can be mapped to 50 the genome using quantitative trait locus (QTL) analysis. Standard QTL mapping for many 51 different species is based on recombinant inbred lines (RILs) derived from a cross between two 52 genetically and phenotypically divergent parents. One of the many species that has extensively 53 been used for exploring the genetics of complex traits is the bacterivorous nematode 54 Caenorhabditis elegans [3, 4]. 55Genetic diversity between C. elegans populations on a local scale can be almost as diverse 56 as on a global scale, with genetically distinct populations occurring within a few kilometers 57 distance [5-9] and it is likely that both local adaptation and local competition between genotypes 58 are critical for the species [1, 2, 10]. Most inbred mapping populations of C. elegans were derived 59 from two glo...