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Title: Natural variation in lifespan and stress responses in Caenorhabditis elegans
Author: Stastna, Jana J.
ISNI:       0000 0004 6350 7765
Awarding Body: Canterbury Christ Church University
Current Institution: Canterbury Christ Church University
Date of Award: 2016
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Wild animals are adapted to survive in different niches and therefore represent a great source for natural variation studies. Mapping of complex traits in model organisms has, for some time been constrained by low genetic variation of laboratory cultured strains. Although informative, this approach is fairly limiting. Recently, research in many model species has benefited from the creation of multi-parental crosses derived from wild-caught strains. Studying natural genetic variation using this approach allows for a better understanding of gene function as allelic interactions in divergent genetic backgrounds play important roles in determining complex traits. Such an approach was notably missing in Caenorhabditis elegans research. To remedy this, a new 4-parental recombination inbred line (RIL) panel that is representative of genotypically distinct groups of C. elegans isolates and distinct from the canonical N2 strain has been created. In this thesis I have used C. elegans, that has a short lifespan, high fecundity and wide array of genetic and genomic resources, to investigate variation in lifespan, its related traits and in the response to dietary restriction (DR). My specific aims were to further characterise a number of previously isolated lifespan QTLs, and to analyse lifespan and stress resistance in a new panel of 4-parent RILs. This work has discovered that the effect of DR on lifespan in C. elegans varies between genotypes and that such differences are seen in introgression lines (ILs), RILs and in wild isolates. A wide review of the literature on DR shows support for the view that genotype-specific effects on lifespan are widespread and that for some genotypes DR can be deleterious. I have also discovered that the newly created 4- parental panel of RILs contains significant, ecologically relevant, variation in lifespan and in stress resistance, that lifespan and stress resistance; are not correlated in these lines, and that this can be used to identify quantitative trait loci (QTLs) controlling this variation. Importantly, some of these QTLs cannot be explained by known lifespan regulating genes. Furthermore, the analyses revealed that the cold stress resistance in C. elegans is related to the control of translation, that the major QTLs detected in the RILs cannot be a consequence of genes known to be involved in cold stress resistance and that one may be a consequence of variation in eftu- 2 a part of the translation machinery. These results highlight the importance of exploring various genetic backgrounds in quantitative genetics and present a wider picture of the genetic interactions that are likely to be happening in the wild.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QL Zoology