Abstract:
:Linking the molecular effects of mutations to fitness is central to understanding evolutionary dynamics. Here, we establish a quantitative relation between the global effect of mutations on the E. coli proteome and bacterial fitness. We created E. coli strains with specific destabilizing mutations in the chromosomal folA gene encoding dihydrofolate reductase (DHFR) and quantified the ensuing changes in the abundances of 2,000+ E. coli proteins in mutant strains using tandem mass tags with subsequent LC-MS/MS. mRNA abundances in the same E. coli strains were also quantified. The proteomic effects of mutations in DHFR are quantitatively linked to phenotype: the SDs of the distributions of logarithms of relative (to WT) protein abundances anticorrelate with bacterial growth rates. Proteomes hierarchically cluster first by media conditions, and within each condition, by the severity of the perturbation to DHFR function. These results highlight the importance of a systems-level layer in the genotype-phenotype relationship.
journal_name
Cell Repjournal_title
Cell reportsauthors
Bershtein S,Choi JM,Bhattacharyya S,Budnik B,Shakhnovich Edoi
10.1016/j.celrep.2015.03.051subject
Has Abstractpub_date
2015-04-28 00:00:00pages
645-56issue
4issn
2211-1247pii
S2211-1247(15)00342-3journal_volume
11pub_type
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