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ENVIRONMENT-DEPENDENT CAUSES AND CONSEQUENCES OF MUTATION IN SACCHAROMYCES CEREVISIAE

Environmental effects on mutation have been documented for many years but have
concentrated on agents that directly interact with DNA. Mutation research in its early
history investigated a variety of more mundane environmental factors at levels that
inhibited biological function and attempted to characterize their mutagenicity. This
thesis revisits these old questions armed with more modern methods. It consists of one
review chapter and three experimental chapters. The review chapter proposes that
biological organization itself acts to direct mutation pressure, and that many mutations
are context dependent within this organization. Experimentally, I performed an
approximately 1,500-generation mutation accumulation (MA) experiment using the
budding yeast Saccharomyces cerevisiae as an evolutionary genetic model. This thesis
investigates the rates and distribution of effects of new mutations on fitness when they
accumulate under a moderate salt stress. The first experimental section describes the
production of the MA lines, measures the diploid fitness traits mitotic growth rate and
sporulation, and uses changes in fitness among replicate lines to infer mutation
parameters affecting these traits. Mutation rate estimates for these traits were roughly
doubled in the salt stress treatment. The proportion of beneficial mutations was high
for mutations affecting sporulation in both MA treatments but zero for growth rate.
Measurements of haploid viability and haploid growth rate on strains derived from the
diploid MA lines were used to infer mutation parameters. Mutation rates affecting
haploid growth were ten-fold higher in our salt-line derivatives than those derived from
the non-stress treatment. Variance component analysis identified a large fraction of
genetic variation arising from differences among haploids within the same tetrad. This
component was significantly larger in the salt MA treatment than the non-stress
treatment. MA lines were subjected to a novel weak-acid stress. Mutation rate
estimates were 38-fold higher in the salt MA treatment when lines were tested under
acid stress. Cross-environmental genetic correlation for growth in acid stress versus
standard media was significantly different between the two MA treatments suggesting
that both MA environment and test environment are important factors when considering
mutational effects on fitness.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:NSHD.ca#10222/14821
Date18 April 2012
CreatorsKozela, Christopher Paul
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish

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