Understanding the evolutionary implications of gene duplications and mechanisms of their maintenance in long-term evolutionary timescales

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5m

Speaker

Subrata Mishra (Affiliation )

Description

Gene duplications have been proven to introduce variation by providing basic genetic material mainly those with adaptive functions. The pervasive choice of evolutionary pathway in the form of duplications in all three domains of life , including mammals, plants, yeast, bacteria, and archaea has been observed by analysis of their respective genomes. The significance of gene duplication can be gauged from the fact that a large percent of genes in a species are duplicates (A. thaliana and C. elegans have 65% and 49% respectively). Despite being an extremely important mode of bringing about evolutionary change, we have limited understanding of how gene duplication becomes adaptive. This is primarily due to a lack of an experimental system to study aspects of gene duplication. We seek to design evolution experiments where the fate of the duplicate genes can be tracked in real-time. The yeast Saccharomyces cerevisiae is an excellent model system to ask this question. The organism underwent a WGD event, and extant variants have over 500 gene duplicates, serving different functions towards cellular physiology. One such pair of duplicate genes is present in the GAL regulon, which encodes for genes responsible for galactose utilization. Two major components of the Gal switch, GAL3p, a signal transducer and GAL1p, a galactokinase arose after a duplication event. Prior to the WGD event, these two functions were carried out by a single bifunctional protein. K. lactis,another yeast species which did not undergo a WGD event, functions with a single bifunctional protein performing both kinase and inducer functions. Why such a duplication was not seen for the same protein in K.lactis could be a consequence of the environment conditions in which the organism evolved. However, to what extent was the duplication event an adaptive necessity, or was it simply one of the many possible adaptive solutions is not well understood. We use mathematical modeling of the GAL network in S. cerevisiae to design experiments to understand post-duplication divergence in real-time. Based on inputs from the model, we evolve S. cerevisiae populations in high, moderate, low, and fluctuating levels of galactose concentrations. The starting genotype of the ancestral strains is (a) two copies of the signal transducer GAL3, (b) two copies of the galactokinase GAL1, (c) two copies of the K. lactis bifunctional GAL1 (d) two copies of GAL1 with mitigated kinase and signal transducing activities. Additionally, control experiments with only a single copy of each of the three genes were also performed. Long-term, our goal is to use the GAL system in S. cerevisiae as a model system to study real-time kinetics of gene duplication and diversification.

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