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Intermittent select...
Intermittent selection directs evolution of a specialist enzyme to become a generalist
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- Abdalaal, Hind (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Uppsala university,Joakim Näsvall
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- Näsvall, Joakim (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Joakim Näsvall
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(creator_code:org_t)
- Engelska.
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- A mutation that introduces a new enzymatic function can be accompanied by a trade-off between the original function and the new function. We previously tested the evolutionary trajectories of Salmonella enterica HisA enzyme (catalyze the fourth step in histidine biosynthesis) towards TrpF activity (catalyze the third step in tryptophan biosynthesis). The majority of the mutations that introduced TrpF activity led to a complete loss of detectable HisA activity. In the rare hisA mutants that kept HisA activity, HisA activity was lost when selecting for mutations that improved TrpF activity. However, some natural HisA orthologs had dual (HisA and TrpF) activities, which has evolved from a specialist HisA.The present study was designed to investigate whether Salmonella enterica HisA can evolve into a generalist (HisA+TrpF) enzyme, despite the strong trade-off between the original function and the new function. Therefore, we allowed trpF-deleted Salmonella enterica with or without a mutator phenotype to evolve in a low concentration of tryptophan. This allowed it to grow for a few generations in relaxed selection, which was followed by several days of strong selection (tryptophan depletion). In this setup, it was never lethal to not have TrpF activity, but it would be lethal to lose HisA activity.These cycled lineages circumvented the tryptophan starvation by loss of function in the tryptophan biosynthesis pathway or by accumulating mutations in hisA gene. The accumulated mutations introduced bifunctionality to the hisA alleles, which was more common in the lineages with the mutator phenotype. These alleles became increasingly efficient in performing both functions when evolved further using the same conditions. Our results indicate that it is possible to evolve an efficient generalist HisA when we use a selection condition that is more likely to occur in nature (a fluctuating environment).
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Nyckelord
- Biologi med inriktning mot mikrobiologi
- Biology with specialization in Microbiology
- Biologi med inriktning mot molekylär evolution
- Biology with specialization in Molecular Evolution
Publikations- och innehållstyp
- vet (ämneskategori)
- ovr (ämneskategori)