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Evolution. Systematic humanization of yeast genes reveals conserved functions and genetic modularity
Aashiq H Kachroo1, Jon M Laurent1, Christopher M Yellman1
1Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
Science (New York, N.Y.)
|May 23, 2015
Summary
Essential gene functions are conserved across a billion years of evolution. Human genes can replace yeast genes, showing conserved functions are maintained in specific biological pathways.
Area of Science:
- Evolutionary biology
- Molecular genetics
- Genomics
Background:
- Understanding gene function conservation across vast evolutionary timescales is crucial for deciphering evolutionary principles.
- Investigating deep evolutionary divergence requires examining the functional compatibility of genes between species separated by significant evolutionary distances.
Purpose of the Study:
- To determine if genes retain ancestral functions over a billion years of evolution.
- To identify principles governing deep evolutionary divergence by assessing functional conservation.
- To explore the extent to which human genes can functionally replace essential yeast genes.
Main Methods:
- Replaced 414 essential yeast genes with their human orthologs.
- Assayed for complementation of lethal growth defects upon loss of yeast genes.
- Utilized computational simulations to confirm functional maintenance despite sequence divergence.
Main Results:
- Nearly half (47%) of essential yeast genes could be functionally replaced by their human orthologs.
- Gene replaceability was not solely predicted by sequence similarity or expression levels.
- Replaceability strongly depended on gene's involvement in specific biological modules or pathways, such as sterol biosynthesis versus DNA replication initiation.
Conclusions:
- Critical ancestral functions of many essential genes are retained over a billion years of evolution.
- Functional conservation is maintained in a pathway-specific manner, demonstrating resilience to sequence, splicing, and protein interface divergence.
- Selection for specific biological functions plays a key role in maintaining gene replaceability across deep evolutionary time.
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