Abstract:
:Negative genetic regulators of phenotypic heterogeneity, or phenotypic capacitors/stabilizers, elevate population-average fitness by limiting deviation from the optimal phenotype and increase the efficacy of natural selection by enhancing the phenotypic differences among genotypes. Stabilizers can presumably be switched off to release phenotypic heterogeneity in the face of extreme or fluctuating environments to ensure population survival. This task could, however, also be achieved by positive genetic regulators of phenotypic heterogeneity, or "phenotypic diversifiers", as shown by recently reported evidence that a bacterial divisome factor enhances antibiotic resistance. We hypothesized that such active creation of phenotypic heterogeneity by diversifiers, which is functionally independent of stabilizers, is more common than previously recognized. Using morphological phenotypic data from 4,718 single-gene-knockout strains of Saccharomyces cerevisiae, we systematically identified 324 stabilizers and 160 diversifiers and constructed a bipartite network between these genes and the morphological traits they control. Further analyses showed that, compared with stabilizers, diversifiers tended to be weaker and more promiscuous (regulating more traits) regulators targeting traits unrelated to fitness. Moreover, there is a general division of labor between stabilizers and diversifiers. Finally, by incorporating NCI-60 human cancer cell line anticancer drug screening data, we found that human one-to-one orthologs of yeast diversifiers/stabilizers likely regulate the anticancer drug resistance of human cancer cell lines, suggesting that these orthologs are potential targets for auxiliary treatments. Our study therefore highlights stabilizers and diversifiers as the genetic regulators for the bidirectional control of phenotypic heterogeneity, as well as their distinct evolutionary roles and functional independence.
journal_name
Mol Biol Evoljournal_title
Molecular biology and evolutionauthors
Mo N,Zhang X,Shi W,Yu G,Chen X,Yang JRdoi
10.1093/molbev/msaa332subject
Has Abstractpub_date
2020-12-23 00:00:00eissn
0737-4038issn
1537-1719pii
6046000pub_type
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journal_title:Molecular biology and evolution
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2004-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a040649
更新日期:1991-05-01 00:00:00
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journal_title:Molecular biology and evolution
pub_type: 信件
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更新日期:2012-05-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular biology and evolution
pub_type: 杂志文章
doi:10.1093/oxfordjournals.molbev.a026348
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journal_title:Molecular biology and evolution
pub_type: 杂志文章
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更新日期:2020-11-01 00:00:00