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Biochemical mechanisms determine the functional compatibility of heterologous genes
Elucidating the factors governing the functional compatibility of horizontally transferred genes is important to understand bacterial evolution, including the emergence and spread of antibiotic resistance, and to successfully engineer biological systems. In silico efforts and work using single-gene...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802803/ https://www.ncbi.nlm.nih.gov/pubmed/29410400 http://dx.doi.org/10.1038/s41467-018-02944-3 |
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author | Porse, Andreas Schou, Thea S. Munck, Christian Ellabaan, Mostafa M. H. Sommer, Morten O. A. |
author_facet | Porse, Andreas Schou, Thea S. Munck, Christian Ellabaan, Mostafa M. H. Sommer, Morten O. A. |
author_sort | Porse, Andreas |
collection | PubMed |
description | Elucidating the factors governing the functional compatibility of horizontally transferred genes is important to understand bacterial evolution, including the emergence and spread of antibiotic resistance, and to successfully engineer biological systems. In silico efforts and work using single-gene libraries have suggested that sequence composition is a strong barrier for the successful integration of heterologous genes. Here we sample 200 diverse genes, representing >80% of sequenced antibiotic resistance genes, to interrogate the factors governing genetic compatibility in new hosts. In contrast to previous work, we find that GC content, codon usage, and mRNA-folding energy are of minor importance for the compatibility of mechanistically diverse gene products at moderate expression. Instead, we identify the phylogenetic origin, and the dependence of a resistance mechanism on host physiology, as major factors governing the functionality and fitness of antibiotic resistance genes. These findings emphasize the importance of biochemical mechanism for heterologous gene compatibility, and suggest physiological constraints as a pivotal feature orienting the evolution of antibiotic resistance. |
format | Online Article Text |
id | pubmed-5802803 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58028032018-02-09 Biochemical mechanisms determine the functional compatibility of heterologous genes Porse, Andreas Schou, Thea S. Munck, Christian Ellabaan, Mostafa M. H. Sommer, Morten O. A. Nat Commun Article Elucidating the factors governing the functional compatibility of horizontally transferred genes is important to understand bacterial evolution, including the emergence and spread of antibiotic resistance, and to successfully engineer biological systems. In silico efforts and work using single-gene libraries have suggested that sequence composition is a strong barrier for the successful integration of heterologous genes. Here we sample 200 diverse genes, representing >80% of sequenced antibiotic resistance genes, to interrogate the factors governing genetic compatibility in new hosts. In contrast to previous work, we find that GC content, codon usage, and mRNA-folding energy are of minor importance for the compatibility of mechanistically diverse gene products at moderate expression. Instead, we identify the phylogenetic origin, and the dependence of a resistance mechanism on host physiology, as major factors governing the functionality and fitness of antibiotic resistance genes. These findings emphasize the importance of biochemical mechanism for heterologous gene compatibility, and suggest physiological constraints as a pivotal feature orienting the evolution of antibiotic resistance. Nature Publishing Group UK 2018-02-06 /pmc/articles/PMC5802803/ /pubmed/29410400 http://dx.doi.org/10.1038/s41467-018-02944-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Porse, Andreas Schou, Thea S. Munck, Christian Ellabaan, Mostafa M. H. Sommer, Morten O. A. Biochemical mechanisms determine the functional compatibility of heterologous genes |
title | Biochemical mechanisms determine the functional compatibility of heterologous genes |
title_full | Biochemical mechanisms determine the functional compatibility of heterologous genes |
title_fullStr | Biochemical mechanisms determine the functional compatibility of heterologous genes |
title_full_unstemmed | Biochemical mechanisms determine the functional compatibility of heterologous genes |
title_short | Biochemical mechanisms determine the functional compatibility of heterologous genes |
title_sort | biochemical mechanisms determine the functional compatibility of heterologous genes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802803/ https://www.ncbi.nlm.nih.gov/pubmed/29410400 http://dx.doi.org/10.1038/s41467-018-02944-3 |
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