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dc.contributor.authorChiu, Hsuan-Chao
dc.contributor.authorMarx, Christopher J
dc.contributor.authorSegrè, Daniel
dc.date.accessioned2014-02-20T20:58:42Z
dc.date.issued2012
dc.identifier.citationChiu, Hsuan-Chao, Christopher J. Marx, and Daniel Segrè. 2012. Epistasis from functional dependence of fitness on underlying traits. Proceedings of the Royal Society B: Biological Sciences 279(1745): 4156-4164.en_US
dc.identifier.issn0962-8452en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11726252
dc.description.abstractEpistasis between mutations in two genes is thought to reflect an interdependence of their functions. While sometimes epistasis is predictable using mechanistic models, its roots seem, in general, hidden in the complex architecture of biological networks. Here, we ask how epistasis can be quantified based on the mathematical dependence of a system-level trait (e.g. fitness) on lower-level traits (e.g. molecular or cellular properties). We first focus on a model in which fitness is the difference between a benefit and a cost trait, both pleiotropically affected by mutations. We show that despite its simplicity, this model can be used to analytically predict certain properties of the ensuing distribution of epistasis, such as a global negative bias, resulting in antagonism between beneficial mutations, and synergism between deleterious ones. We next extend these ideas to derive a general expression for epistasis given an arbitrary functional dependence of fitness on other traits. This expression demonstrates how epistasis relative to fitness can emerge despite the absence of epistasis relative to lower level traits, leading to a formalization of the concept of independence between biological processes. Our results suggest that epistasis may be largely shaped by the pervasiveness of pleiotropic effects and modular organization in biological networks.en_US
dc.description.sponsorshipOrganismic and Evolutionary Biologyen_US
dc.language.isoen_USen_US
dc.publisherThe Royal Societyen_US
dc.relation.isversionofdoi:10.1098/rspb.2012.1449en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3441082/pdf/en_US
dash.licenseLAA
dc.titleEpistasis from functional dependence of fitness on underlying traitsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalProceedings of the Royal Society B: Biological Sciencesen_US
dash.depositing.authorMarx, Christopher J
dc.date.available2014-02-20T20:58:42Z
dc.identifier.doi10.1098/rspb.2012.1449*
dash.contributor.affiliatedMarx, Christopher J


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