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The duplicated deacetylases Sir2 and Hst1 subfunctionalized by acquiring complementary inactivating mutations
1Department of Biochemistry, Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina 27708, USA.
Molecular and Cellular Biology
|June 22, 2011
Summary
Gene duplication allows protein families to diversify. Researchers found that yeast deacetylases Sir2 and Hst1 acquired distinct functions through complementary mutations in their interaction domains after gene duplication.
Area of Science:
- Molecular Biology
- Evolutionary Genetics
- Yeast Genetics
Background:
- Protein families evolve through gene duplication and diversification.
- The mechanisms by which duplicated genes acquire new functions are not fully understood.
- Investigating Saccharomyces cerevisiae deacetylases Sir2 and Hst1 provides insight into subfunctionalization.
Purpose of the Study:
- To characterize the functional divergence of duplicated deacetylase genes.
- To understand how Saccharomyces cerevisiae Sir2 and Hst1 acquired distinct functions.
- To examine the evolutionary paths of interaction domains in duplicated genes.
Main Methods:
- Comparative analysis of interaction domains between Saccharomyces cerevisiae Sir2 and Hst1.
- Utilized Kluyveromyces lactis Sir2 as a proxy for the ancestral deacetylase.
- Investigated the role of specific amino acid substitutions in disrupting interaction domains.
Main Results:
- Interaction domains for the Sir transcriptional silencing complex (ScSir2) and Sum1 repressor (ScHst1) were conserved.
- These interaction domains can be inactivated by simple amino acid substitutions.
- Sir2 and Hst1 subfunctionalized by accumulating complementary inactivating mutations.
Conclusions:
- Subfunctionalization of duplicated genes can occur through complementary inactivating mutations.
- Evolutionary retention and subsequent disruption of interaction domains play a key role in gene functional diversification.
- This study elucidates a mechanism for how duplicated genes acquire distinct roles in cellular processes.
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