Hypomutable regions of yeast TFIIB in a unigenic evolution test represent structural domains
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Updated: Sep 26, 2026

Targeted in Situ Mutagenesis of Histone Genes in Budding Yeast
Published on: January 26, 2017
Xiao Zeng1, Dongyi Zhang, Michael Dorsey
1Division of Developmental Biology, Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Abstract:
As genome sequences of many organisms - including humans - are being decoded, there is a great need for genetic tools to analyze newly discovered genes/proteins. A 'unigenic evolution' approach has been previously proposed for dissecting protein domains, which is based on the assumption that functionally important regions of a protein may tolerate missense mutations less well than other regions. We describe a unigenic evolution analysis of general transcription factor IIB (TFIIB) - a protein that is well characterized both structurally and functionally - to better understand the molecular basis of this genetic approach. The overall distribution profile of hypomutable regions within yeast TFIIB correlates extremely well with the known compact structural domains, suggesting that the unigenic evolution approach can help reveal structural properties of a protein. We further show that a small region located immediately carboxyl-terminal to the zinc ribbon motif is functionally important despite its strong hypermutability. Our study further demonstrates the usefulness of the unigenic evolution approach in dissecting protein domains, but suggests that the mutability of different regions of a protein in such a test is determined primarily by their structural properties.
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