The persistence of haploinsufficiency and its role in genome evolution

In diploid organisms there are two copies of every gene, one from each parent. While the majority of genes are robust to deletion of one of the two copies, a subset of genes remains highly dosage sensitive, causing a significant decrease in fitness when heterozygously deleted. These genes, known as haploinsufficient (HI) genes, are present in eukaryotic species from yeast to humans. Why haploinsufficiency persists over evolutionary time is not known. To answer this, I systematically tested two existing models of haploinsufficiency: 1) the dosage stabilizing hypothesis, which states that haploinsufficiency is caused by imbalances among protein complex members, and 2) the insufficient amounts hypothesis, which says that haploinsufficient gene products are limiting for growth. In this thesis I find that having a single extra copy of haploinsufficient genes was sufficient to cause a growth defect in Saccharomyces cerevisiae.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2020

Author dc:creator

• Morrill, Summer Ashlee.

Advisor dc:contributor.advisor

• Angelika Amon.

• Biology.

Statement dc:rights

• MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.

Licence dc:rights.uri

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

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/129024

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/129024