Presented By: Department of Computational Medicine and Bioinformatics DCMB
DCMB Tools and Technology Seminar by Yang Li
“Navigability of thousands of adaptive landscapes of RNA and protein expressions by trans-regulatory mutations”
Abstract
Gene expression evolution relies on regulatory mutations. Past studies suggested that optimizing gene expression by positive selection on cis-regulatory mutations is relatively easy because the corresponding adaptive landscapes are quite smooth. To what extent gene expression can be optimized via trans-regulatory mutations is, however, unknown. Analyzing the transcriptomes and proteomes of 16 yeast strains carrying all combinations of four auxotrophic mutations, we respectively construct 5,923 and 446 adaptive landscapes of mRNA and protein expressions where neighboring genotypes differ by a trans-regulatory mutation. We find that mRNA expression is less optimizable by trans-regulatory mutations than by cis-regulatory mutations due to a lower fraction of open adaptive paths via trans- than cis-changes, which may partially explain why trans-regulatory changes are rarer than cis-regulatory changes in gene expression evolution. Interestingly, the adaptive landscapes of protein expressions are substantially less rugged and thereby more navigable than those of mRNA expressions due to post-transcriptional buffering effects, suggesting that, for protein-coding genes, the evolvability of gene expression is even higher than the current estimate from adaptive landscapes of mRNA expressions. This high evolvability may have contributed to the prominence of gene expression changes as a mechanism of evolutionary adaptation.
About the DCMB Tools & Technology Seminar Series
The DCMB Tools and Technology Seminar Series is held in Medical Science Building 1 (MS1), Room 4B700, each Thursday at 12pm EST. Each seminar highlights a computational tool, technology, or methodology that is under development or in current use and is of special interest to DCMB and University researchers. Presenters are U-M researchers and students.
These seminars are live-streamed and recorded and made available for future viewing via the DCMB YouTube Channel
Gene expression evolution relies on regulatory mutations. Past studies suggested that optimizing gene expression by positive selection on cis-regulatory mutations is relatively easy because the corresponding adaptive landscapes are quite smooth. To what extent gene expression can be optimized via trans-regulatory mutations is, however, unknown. Analyzing the transcriptomes and proteomes of 16 yeast strains carrying all combinations of four auxotrophic mutations, we respectively construct 5,923 and 446 adaptive landscapes of mRNA and protein expressions where neighboring genotypes differ by a trans-regulatory mutation. We find that mRNA expression is less optimizable by trans-regulatory mutations than by cis-regulatory mutations due to a lower fraction of open adaptive paths via trans- than cis-changes, which may partially explain why trans-regulatory changes are rarer than cis-regulatory changes in gene expression evolution. Interestingly, the adaptive landscapes of protein expressions are substantially less rugged and thereby more navigable than those of mRNA expressions due to post-transcriptional buffering effects, suggesting that, for protein-coding genes, the evolvability of gene expression is even higher than the current estimate from adaptive landscapes of mRNA expressions. This high evolvability may have contributed to the prominence of gene expression changes as a mechanism of evolutionary adaptation.
About the DCMB Tools & Technology Seminar Series
The DCMB Tools and Technology Seminar Series is held in Medical Science Building 1 (MS1), Room 4B700, each Thursday at 12pm EST. Each seminar highlights a computational tool, technology, or methodology that is under development or in current use and is of special interest to DCMB and University researchers. Presenters are U-M researchers and students.
These seminars are live-streamed and recorded and made available for future viewing via the DCMB YouTube Channel