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The composition and evolution of C. elegans behavioural genetic architectures

Periodic Reporting for period 1 - EvolBehavGenArch (The composition and evolution of C. elegans behavioural genetic architectures)

Berichtszeitraum: 2018-09-03 bis 2020-09-02

The maintenance of genetic diversity in the face of neutral and non-neutral processes that continually erode it is one of the longstanding puzzles of biology. Natural selection shapes the genetic variation provided by mutation, segregation and recombination to (generally) improve fitness, but it is often difficult to obtain measures of fitness and genetic variation in the interesting, but uncontrolled, natural environments in which we find organisms. A related question is the heritable basis of phenotypic variance. Knowing the genetic architectures of well-defined traits – the number and type of loci that contribute to phenotypic variance, and the distribution and conditionality of their effects – is central to our general understanding of evolutionary processes, and for our ability to predict phenotypes of interest in agriculture and medicine. In this context, the genetic basis of behavioural variation is particularly fascinating and poorly understood.

Caenorhabditis elegans is an exceptional model system with which to tackle these problems, and experimental evolution provides exceptional power to dissect genetic architectures of well-defined behavioural traits and their dynamic properties under controlled conditions.

The proposed research aimed to advance our understanding of how trait correlations shape the distribution of genetic variance, and reveal the composition and evolution of behavioural genetic architectures shaped by natural selection.
We expanded the C. elegans Multiparent Experimental Evolution genetic resource, a collection of more than 750 recombinant inbred lines, and the replicated outbred populations from which they were derived, now spanning more than 240 generations of adaptation to lab conditions. Large collections of genomic and phenotypic data were generated, curated, analysed, and made available to the community in the process through existing open access repositories and a new website. A preprint was submitted, and this work is under review.

We measured the locomotion of individuals, from an equivalent of 42 days imaging in total over 2012 to 2019, and analysed the genetic structuring of multiple traits through evolution. We found first that populations rapidly attained a new optimum value of trait combinations during domestication to the new environment. Subsequently, we found that the structure of traits evolves, despite stasis at the level of individual trait means, and that evolution under our constant environment occurs mainly through many alleles with small effects. A preprint was submitted, and this work is under review.

By testing for association between genetic markers and trait variance, we also found a small number of loci with moderate additive and epistatic effects on some individual traits. One such allele is a loss-of-function mutation introduced in the genetic background of the C. elegans reference strain, N2, that we discovered. This allele modifies the effects of natural genetic variation on the locomotion and shape of CeMEE RILs, and the effects of classical cuticle mutations that have been extensively studied since the introduction of C. elegans as a model genetic system. A preprint was submitted, and this work has been peer reviewed.

Reorientation of some activity due to the pandemic resulted in a study on population genomics of a related species, also capable of reproducing by hermaphrodite self-fertilisation, C. tropicalis. This study implicated balancing selection across a global range in the maintenance of genetic diversity, despite a very high rate of selfing relative to C. elegans. We also generated foundational genetic and genomic resources for this species, furthering comparative biology in the genus. A preprint was submitted, which has now been accepted for publication.
An improved understanding of the evolution of multiple traits and the genetic basis of behaviour in simple biological systems. Generation of permanent genetic and phenotypic resources for two species for use by the Caenorhabditis research community.
Reconstructed founder haplotypes in CeMEE recombinant inbred lines
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