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

摘要: Horizontal gene transfer (HGT) plays a central role in bacterial evolution, yet the molecular and cellular constraints on functional integration of foreign genes are poorly understood. Here we performed inter-species replacement chromosomal folA gene, encoding an essential metabolic enzyme dihydrofolate reductase (DHFR), with orthologs from 35 other mesophilic bacteria. The orthologous replacements caused marked drop (in range 10-90%) growth rate despite fact that most DHFRs as stable E.coli DHFR at 37°C more catalytically active than E. coli DHFR. Although phylogenetic distance between well their individual properties correlate rates, product intracellular abundance catalytic activity (kcat/KM), correlates strongly indicating constitutes major fitness barrier to HGT. Serial propagation strains for ~600 generations dramatically improved rates by largely alleviating barriers. Whole genome sequencing global proteome quantification revealed evolved largest improvements have accumulated mutations inactivated ATP-dependent Lon protease, causing increase abundance. In one case increased further due promoter, but only after lon inactivating were fixed population. Thus, apparently distinguishing self non-self proteins, protein homeostasis imposes immediate decreasing products. Once this is alleviated, fine-tuned evolution occurs adjust function/expression transferred proteins imposed environment host organism.