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Evolutionary footprint of epistasis
Gabriele Pedruzzi1, Ayuna Barlukova1, Igor M Rouzine1
1Sorbonne Université, Institute de Biologie Paris-Seine, Laboratoire de Biologie Computationelle et Quantitative, Paris, France.
Plos Computational Biology
|September 18, 2018
Summary
Epistasis, or gene interactions, significantly impacts evolution and adaptation. This study reveals a universal relationship in haplotype frequencies, aiding in detecting compensatory mutations for biomedical applications.
Area of Science:
- Population Genetics
- Evolutionary Biology
- Genomics
Background:
- Genetic variation is influenced by gene interactions (epistasis), not just additive gene effects.
- Detecting epistasis in genomic data is challenging and requires mechanistic understanding.
Purpose of the Study:
- To investigate the impact of compensatory epistasis on population adaptation using a Wright-Fisher model.
- To establish a universal relationship for haplotype frequencies influenced by epistasis.
Main Methods:
- Utilized a standard Wright-Fisher model for bi-allelic asexual populations.
- Employed Monte-Carlo simulations to verify analytical results across various parameters.
- Developed a method to determine selection coefficients and epistasis strength from sequence data.
Main Results:
- Derived a universal relationship between four haplotype frequencies, dependent on epistasis strength.
- Demonstrated a quasi-equilibrium between epistasis and genetic drift/mutation.
- Showcased epistasis's role in facilitating evolutionary transitions and leaving marks on haplotype disequilibrium.
Conclusions:
- Epistasis plays a crucial role in adaptation and evolutionary processes.
- The developed method enables the detection of deleterious mutation clusters and compensatory mutations.
- Findings are essential for understanding viral resistance and immune responses, with biomedical applications.
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