Genetic and epigenetic regulation of the cell wall glycoproteins, Flo10p and Flo11p, generate phenotypic variation in S. cerevisiae

Many organisms, in response to selective pressures imposed by their environment, have evolved mechanisms that allow them to generate phenotypic variation. Such phenotypic variation can result from genetic regulation, in which changes in DNA sequence produce the variant phenotype, or epigenetic regulation, in which there are no changes in DNA sequence associated with the variant phenotype. This doctoral thesis describes the identification and analysis of novel phenotypic variation among populations of the bakers' yeast, Saccharomyces cerevisiae. This phenotypic variation, most easily identified as a switching between smooth and wrinkled colony morphologies, involves changes in several adhesive and morphological phenotypes. Experiments reveal that this phenotypic switch is the result of both genetic and epigenetic regulation. The genetic component of this phenotypic variation involves mutation at either of the two yeast Ras-GAP encoding genes, IRA] and IRA2. The IRA genes are hot spots for mutation, as loss-of-function mutations at these genes are much more frequent than mutations at other loci (- 10-6). Several factors regulate the genetic stability of these genes, including DNA double-strand break (DSB) repair pathways. Genetic analysis demonstrates that both homologous recombination (HR) and non-homologous end-joining (NHEJ) pathways of DSB repair maintain genetic stability at the IRA loci. Since these pathways specifically process a DSB substrate, this suggests that directed DSB formation may be the initiating event for IRA+ to ira- switching. ira- mutations activate transcription of the yeast cell wall glycoprotein genes, FLOO0 and FLO11, producing the variant adhesive and morphological phenotypes described above.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2003

Author dc:creator

• Halme, Adrian Jones, 1971-

Advisor dc:contributor.advisor

• Gerald R. Fink.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/29942

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/29942