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Cryptic genetic var...
Cryptic genetic variation shapes the adaptive evolutionary potential of enzymes
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- Baier, Florian (author)
- Univ British Columbia, Michael Smith Lab, Vancouver, BC, Canada
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- Hong, Nansook (author)
- Australian Natl Univ, Res Sch Chem, Canberra, ACT, Australia
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- Yang, Gloria (author)
- Univ British Columbia, Michael Smith Lab, Vancouver, BC, Canada
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- Pabis, Anna (author)
- Uppsala universitet,Molekylär biofysik
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- Miton, Charlotte M. (author)
- Univ British Columbia, Michael Smith Lab, Vancouver, BC, Canada
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- Barrozo, Alexandre (author)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
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- Carr, Paul D. (author)
- Australian Natl Univ, Res Sch Chem, Canberra, ACT, Australia
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- Kamerlin, Shina C. Lynn, 1981- (author)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
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- Jackson, Colin J. (author)
- Australian Natl Univ, Res Sch Chem, Canberra, ACT, Australia
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- Tokuriki, Nobuhiko (author)
- Univ British Columbia, Michael Smith Lab, Vancouver, BC, Canada
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(creator_code:org_t)
- ELIFE SCIENCES PUBLICATIONS LTD, 2019
- 2019
- English.
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In: eLIFE. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 8
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https://uu.diva-port... (primary) (Raw object)
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Abstract
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- Genetic variation among orthologous proteins can cause cryptic phenotypic properties that only manifest in changing environments. Such variation may impact the evolvability of proteins, but the underlying molecular basis remains unclear. Here, we performed comparative directed evolution of four orthologous metallo-beta-lactamases toward a new function and found that different starting genotypes evolved to distinct evolutionary outcomes. Despite a low initial fitness, one ortholog reached a significantly higher fitness plateau than its counterparts, via increasing catalytic activity. By contrast, the ortholog with the highest initial activity evolved to a less-optimal and phenotypically distinct outcome through changes in expression, oligomerization and activity. We show how cryptic molecular properties and conformational variation of active site residues in the initial genotypes cause epistasis, that could lead to distinct evolutionary outcomes. Our work highlights the importance of understanding the molecular details that connect genetic variation to protein function to improve the prediction of protein evolution.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Baier, Florian
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Hong, Nansook
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Yang, Gloria
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Pabis, Anna
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Miton, Charlotte ...
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Barrozo, Alexand ...
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show more...
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Carr, Paul D.
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Kamerlin, Shina ...
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Jackson, Colin J ...
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Tokuriki, Nobuhi ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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eLIFE
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Uppsala University