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Protein Homeostasis Imposes a Barrier on Functional Integration of Horizontally Transferred Genes in Bacteria


Horizontal gene transfer (HGT) is central to bacterial evolution. The outcome of an HGT event (fixation in a population, elimination, or separation as a subdominant clone) depends not only on the availability of a new gene but crucially on the fitness cost or benefit of the genomic incorporation of the foreign gene and its expression in recipient bacteria. Here we studied the fitness landscape for inter-species chromosomal replacement of an essential protein, dihydrofolate reductase (DHFR) encoded by the folA gene, by its orthologs from other mesophilic bacteria. We purified and biochemically characterized 33 out of 35 orthologous DHFRs and found that most of them are stable and more catalytically active than E. coli DHFR. However, the inter-species replacement of DHFR caused significant fitness loss for most transgenic strains due to low abundance of orthologous DHFRs in E. coli cytoplasm. Laboratory evolution resulted in an increase in orthologous DHFR abundance leading to a dramatic fitness improvement. Genomic and proteomic analyses of “naive” and evolved strains suggest a new function of protein homeostasis to discriminate between “self” and “non-self” proteins, thus creating fitness barriers to HGT.


Vyšlo v časopise: Protein Homeostasis Imposes a Barrier on Functional Integration of Horizontally Transferred Genes in Bacteria. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005612
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005612

Souhrn

Horizontal gene transfer (HGT) is central to bacterial evolution. The outcome of an HGT event (fixation in a population, elimination, or separation as a subdominant clone) depends not only on the availability of a new gene but crucially on the fitness cost or benefit of the genomic incorporation of the foreign gene and its expression in recipient bacteria. Here we studied the fitness landscape for inter-species chromosomal replacement of an essential protein, dihydrofolate reductase (DHFR) encoded by the folA gene, by its orthologs from other mesophilic bacteria. We purified and biochemically characterized 33 out of 35 orthologous DHFRs and found that most of them are stable and more catalytically active than E. coli DHFR. However, the inter-species replacement of DHFR caused significant fitness loss for most transgenic strains due to low abundance of orthologous DHFRs in E. coli cytoplasm. Laboratory evolution resulted in an increase in orthologous DHFR abundance leading to a dramatic fitness improvement. Genomic and proteomic analyses of “naive” and evolved strains suggest a new function of protein homeostasis to discriminate between “self” and “non-self” proteins, thus creating fitness barriers to HGT.


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