scholarly journals Neutral genetic drift can alter promiscuous protein functions, potentially aiding functional evolution

2007 ◽  
Vol 2 (1) ◽  
pp. 17 ◽  
Author(s):  
Jesse D Bloom ◽  
Philip A Romero ◽  
Zhongyi Lu ◽  
Frances H Arnold
Keyword(s):  
Genetic Drift ◽  
Functional Evolution ◽  
Protein Functions ◽  
Neutral Genetic Drift

scholarly journals Shuffling the Neutral Drift of Unspecific Peroxygenase inSaccharomyces cerevisiae

2018 ◽  
Vol 84 (15) ◽  
Author(s):  
Javier Martin-Diaz ◽  
Carmen Paret ◽  
Eva García-Ruiz ◽  
Patricia Molina-Espeja ◽  
Miguel Alcalde
Keyword(s):  
Genetic Drift ◽  
Dna Recombination ◽  
Dna Shuffling ◽  
Content Type ◽  
Neutral Drift ◽  
Oxygenase Activity ◽  
Improved Stability ◽  
Neutral Mutations ◽  
Neutral Genetic Drift

ABSTRACTUnspecific peroxygenase (UPO) is a highly promiscuous biocatalyst, and its selective mono(per)oxygenase activity makes it useful for many synthetic chemistry applications. Among the broad repertory of library creation methods for directed enzyme evolution, genetic drift allows neutral mutations to be accumulated gradually within a polymorphic network of variants. In this study, we conducted a campaign of genetic drift with UPO inSaccharomyces cerevisiae, so that neutral mutations were simply added and recombinedin vivo. With low mutational loading and an activity threshold of 45% of the parent's native function, mutant libraries enriched in folded active UPO variants were generated. After only eight rounds of genetic drift and DNA shuffling, we identified an ensemble of 25 neutrally evolved variants with changes in peroxidative and peroxygenative activities, kinetic thermostability, and enhanced tolerance to organic solvents. With an average of 4.6 substitutions introduced per clone, neutral mutations covered approximately 10% of the protein sequence. Accordingly, this study opens new avenues for UPO design by bringing together neutral genetic drift and DNA recombinationin vivo.IMPORTANCEFungal peroxygenases resemble the peroxide shunt pathway of cytochrome P450 monoxygenases, performing selective oxyfunctionalizations of unactivated C-H bonds in a broad range of organic compounds. In this study, we combined neutral genetic drift andin vivoDNA shuffling to generate highly functional peroxygenase mutant libraries. The panel of neutrally evolved peroxygenases showed different activity profiles for peroxygenative substrates and improved stability with respect to temperature and the presence of organic cosolvents, making the enzymes valuable blueprints for emerging evolution campaigns. This association of DNA recombination and neutral drift is paving the way for future work in peroxygenase engineering and, from a more general perspective, to any other enzyme system heterologously expressed inS. cerevisiae.

scholarly journals Neutral Genetic Drift-Based Engineering of a Sucrose-Utilizing Enzyme toward Glycodiversification

ACS Catalysis ◽  
2018 ◽  
Vol 9 (2) ◽  
pp. 1241-1252 ◽  
Author(s):  
David Daudé ◽  
Alizée Vergès ◽  
Emmanuelle Cambon ◽  
Stéphane Emond ◽  
Samuel Tranier ◽  
...  
Keyword(s):  
Genetic Drift ◽  
Neutral Genetic Drift

scholarly journals Cooption of polyalanine tract into a repressor domain in the mammalian transcription factor HoxA11

2020 ◽  
Author(s):  
Vincent J. Lynch ◽  
Gunter P. Wagner
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Amino Acid ◽  
Molecular Mechanisms ◽  
Functional Evolution ◽  
Repeat Number ◽  
Amino Acid Repeats ◽  
Protein Functions ◽  
Stem Lineage ◽  
Polyalanine Tract

AbstractAn enduring problem in biology is explaining how the functions of genes originated and how those functions diverge between species. Despite detailed studies on the functional evolution of a few proteins, the molecular mechanisms by which protein functions have evolved are almost entirely unknown. Here we show that a polyalanine tract in the homeodomain transcription factor HoxA11 arose in the stem-lineage of mammals and functions as an autonomous repressor module by physically interacting with the PAH domains of SIN3 proteins. These results suggest that long polyalanine tracts, which are common in transcription factors and often associated with disease, may generally function as repressor domains and can contribute to the diversification of transcription factor functions despite the deleterious consequences of polyalanine tract expansion.Research HighlightsWe show that a polyalanine track in HoxA11 evolved into a repressor domain in mammals through an increase in alanine repeat number, indicating that transcription factors can evolve novel functions despite the potential deleterious consequences associated with amino acid repeats.

Chaperonin as the normal controls and pathological anti-stress response in the human reproductive system

2016 ◽  
pp. 126-129
Author(s):  
M. Makarenko ◽  
◽  
D. Hovsyeyev ◽  
L. Sydoryk ◽  
◽  
...  
Keyword(s):  
Reproductive System ◽  
Stress Proteins ◽  
Physiological Stress ◽  
Protein Complexes ◽  
Reproductive Function ◽  
Intercellular Signaling ◽  
Toll Like Receptors ◽  
Wide Range ◽  
Protein Functions ◽  
And Function

Different kinds of physiological stress cause mass changes in the cells, including the changes in the structure and function of the protein complexes and in separate molecules. The protein functions is determined by its folding (the spatial conclusion), which depends on the functioning of proteins of thermal shock- molecular chaperons (HSPs) or depends on the stress proteins, that are high-conservative; specialized proteins that are responsible for the correct proteinaceous folding. The family of the molecular chaperones/ chaperonins/ Hsp60 has a special place due to the its unique properties of activating the signaling cascades through the system of Toll-like receptors; it also stimulates the cells to produce anti- inflammatory cytokines, defensins, molecules of cell adhesion and the molecules of MHC; it functions as the intercellular signaling molecule. The pathological role of Hsp60 is established in a wide range of illnesses, from diabetes to atherosclerosis, where Hsp60 takes part in the regulation of both apoptosis and the autoimmune processes. The presence of the HSPs was found in different tissues that are related to the reproductive system. Key words: molecular chaperons (HSPs), Toll-like receptors, reproductive function, natural auto antibody.

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