دورية أكاديمية

Frustration can Limit the Adaptation of Promiscuous Enzymes Through Gene Duplication and Specialisation.

التفاصيل البيبلوغرافية
العنوان: Frustration can Limit the Adaptation of Promiscuous Enzymes Through Gene Duplication and Specialisation.
المؤلفون: Schmutzer M; Department of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland.; Swiss Institute of Bioinformatics, Lausanne, Switzerland., Dasmeh P; Center for Human Genetics, Philipps University of Marburg, Marburg, Germany., Wagner A; Department of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland. andreas.wagner@ieu.uzh.ch.; Swiss Institute of Bioinformatics, Lausanne, Switzerland. andreas.wagner@ieu.uzh.ch.; Santa Fe Institute, Santa Fe, NM, USA. andreas.wagner@ieu.uzh.ch.
المصدر: Journal of molecular evolution [J Mol Evol] 2024 Apr; Vol. 92 (2), pp. 104-120. Date of Electronic Publication: 2024 Mar 12.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 0360051 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1432 (Electronic) Linking ISSN: 00222844 NLM ISO Abbreviation: J Mol Evol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Berlin, New York, Springer-Verlag.
مواضيع طبية MeSH: Gene Duplication* , Frustration*, Catalysis ; Enzymes/genetics
مستخلص: Virtually all enzymes catalyse more than one reaction, a phenomenon known as enzyme promiscuity. It is unclear whether promiscuous enzymes are more often generalists that catalyse multiple reactions at similar rates or specialists that catalyse one reaction much more efficiently than other reactions. In addition, the factors that shape whether an enzyme evolves to be a generalist or a specialist are poorly understood. To address these questions, we follow a three-pronged approach. First, we examine the distribution of promiscuity in empirical enzymes reported in the BRENDA database. We find that the promiscuity distribution of empirical enzymes is bimodal. In other words, a large fraction of promiscuous enzymes are either generalists or specialists, with few intermediates. Second, we demonstrate that enzyme biophysics is not sufficient to explain this bimodal distribution. Third, we devise a constraint-based model of promiscuous enzymes undergoing duplication and facing selection pressures favouring subfunctionalization. The model posits the existence of constraints between the catalytic efficiencies of an enzyme for different reactions and is inspired by empirical case studies. The promiscuity distribution predicted by our constraint-based model is consistent with the empirical bimodal distribution. Our results suggest that subfunctionalization is possible and beneficial only in certain enzymes. Furthermore, the model predicts that conflicting constraints and selection pressures can cause promiscuous enzymes to enter a 'frustrated' state, in which competing interactions limit the specialisation of enzymes. We find that frustration can be both a driver and an inhibitor of enzyme evolution by duplication and subfunctionalization. In addition, our model predicts that frustration becomes more likely as enzymes catalyse more reactions, implying that natural selection may prefer catalytically simple enzymes. In sum, our results suggest that frustration may play an important role in enzyme evolution.
(© 2024. The Author(s).)
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معلومات مُعتمدة: 739874 H2020 European Research Council; 31003A_172887 Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
فهرسة مساهمة: Keywords: Enzyme kinetics; Enzyme promiscuity; Evolution; Evolutionary biophysics; Gene duplication
المشرفين على المادة: 0 (Enzymes)
تواريخ الأحداث: Date Created: 20240312 Date Completed: 20240401 Latest Revision: 20240401
رمز التحديث: 20240401
مُعرف محوري في PubMed: PMC10978624
DOI: 10.1007/s00239-024-10161-4
PMID: 38470504
قاعدة البيانات: MEDLINE
الوصف
تدمد:1432-1432
DOI:10.1007/s00239-024-10161-4