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11.
  • Abdalaal, Hind, et al. (författare)
  • Evolvability of orthologous genes
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • The divergence of orthologous genes is usually attributed to the slow and steady accumulation of neutral or nearly neutral mutations. It is known that present-day orthologous genes have a common ancestor and still perform the same function with about the same performance. Natural orthologs differ from each other not only in sequence, but also in physical properties such as their tolerance of mutations and their potential to evolve new functions. However, we currently have a poor understanding of how mutations that accumulate during the sequence divergence of orthologous genes affect their evolvability.In this study, we generated a library of laboratory-evolved orthologous genes for studying how mutations and combinations of mutations (deleterious and compensatory mutations) affect evolvability. We simulated what could happen during the divergence of orthologous genes where fixation of a deleterious mutation is followed by a compensatory mutation. We have subjected one of histidine biosynthetic genes hisA from Salmonella enterica to alternating rounds of weak selection (by random mutagenesis through error-prone PCR subsequent screens for partial loss of hisA function) followed by strong purifying selection (another round of random mutagenesis and subsequent selection for restored hisA function).The diverging lineages were tested for their ability to evolve TrpF activity and were compared with the WT hisA using a fluctuation test. Our results confirmed that orthologous enzymes had differing abilities to evolve the new function. The HisA orthologs with restored function had evolved adaptive genotypes with higher TrpF activity. We suggest that these orthologs may have a higher stability, which is known to increase evolutionary potential by increasing the tolerance for the otherwise destabilizing mutations that confer the new function. 
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12.
  • Abdalaal, Hind, et al. (författare)
  • Intermittent selection directs evolution of a specialist enzyme to become a generalist
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • 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).  
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18.
  • Abedi, Oscar, et al. (författare)
  • The Covid-19 Opportunity: Creating More Ethical and Sustainable Research Practices
  • 2020
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Contributing to the “Covid-19 and the Social Sciences” essay series, Oscar Abedi, Maria Eriksson Baaz, David Mwambari, Swati Parashar, Anju Oseema Maria Toppo, and James Vincent outline various paths toward reducing field research’s potential for exploitation, especially that of Global South collaborators. The pandemic has highlighted inequalities and immobility that differently affect facilitating researchers and contracting researchers. In response, the authors identify key issues that institutions, publishers, and individual researchers must reflect on in order to counteract these imbalances—and take advantage of an opportunity to fundamentally transform field research into collaborative knowledge production.
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  • Resultat 11-20 av 10661
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