TY - JOUR
T1 - Dynamic epistasis for different alleles of the same gene
AU - Xu, Lin
AU - Barker, Brandon
AU - Gu, Zhenglong
PY - 2012/6/26
Y1 - 2012/6/26
N2 - Epistasis refers to the phenomenon in which phenotypic consequences caused by mutation of one gene depend on one or more mutations at another gene. Epistasis is critical for understanding many genetic and evolutionary processes, including pathway organization, evolution of sexual reproduction, mutational load, ploidy, genomic complexity, speciation, and the origin of life. Nevertheless, current understandings for the genome-wide distribution of epistasis are mostly inferred from interactions among one mutant type per gene, whereas how epistatic interaction partners change dynamically for different mutant alleles of the same gene is largely unknown. Here we address this issue by combining predictions from flux balance analysis and data from a recently published high-throughput experiment. Our results show that different alleles can epistatically interact with very different gene sets. Furthermore, between two random mutant alleles of the same gene, the chance for the allele with more severe mutational consequence to develop a higher percentage of negative epistasis than the other allele is 50∼70% in eukaryotic organisms, but only 20∼30% in bacteria and archaea. We developed a population genetics model that predicts that the observed distribution for the sign of epistasis can speed up the process of purging deleterious mutations in eukaryotic organisms. Our results indicate that epistasis among genes can be dynamically rewired at the genome level, and call on future efforts to revisit theories that can integrate epistatic dynamics among genes in biological systems.
AB - Epistasis refers to the phenomenon in which phenotypic consequences caused by mutation of one gene depend on one or more mutations at another gene. Epistasis is critical for understanding many genetic and evolutionary processes, including pathway organization, evolution of sexual reproduction, mutational load, ploidy, genomic complexity, speciation, and the origin of life. Nevertheless, current understandings for the genome-wide distribution of epistasis are mostly inferred from interactions among one mutant type per gene, whereas how epistatic interaction partners change dynamically for different mutant alleles of the same gene is largely unknown. Here we address this issue by combining predictions from flux balance analysis and data from a recently published high-throughput experiment. Our results show that different alleles can epistatically interact with very different gene sets. Furthermore, between two random mutant alleles of the same gene, the chance for the allele with more severe mutational consequence to develop a higher percentage of negative epistasis than the other allele is 50∼70% in eukaryotic organisms, but only 20∼30% in bacteria and archaea. We developed a population genetics model that predicts that the observed distribution for the sign of epistasis can speed up the process of purging deleterious mutations in eukaryotic organisms. Our results indicate that epistasis among genes can be dynamically rewired at the genome level, and call on future efforts to revisit theories that can integrate epistatic dynamics among genes in biological systems.
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U2 - 10.1073/pnas.1121507109
DO - 10.1073/pnas.1121507109
M3 - Article
C2 - 22689976
AN - SCOPUS:84862999197
SN - 0027-8424
VL - 109
SP - 10420
EP - 10425
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 26
ER -