Hall, Benjamin;
Hall, Michael;
Shorthouse, david;
Alcraft, Rachel;
Jones, Phil;
(2023)
Mutations observed in somatic evolution reveal underlying gene mechanisms.
Communications Biology
, 6
, Article 753. 10.1038/s42003-023-05136-y.
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Abstract
Highly sensitive DNA sequencing techniques have allowed the discovery of large numbers of somatic mutations in normal tissues. Some mutations confer a competitive advantage over wild-type cells, generating expanding clones that spread through the tissue. Competition between mutant clones leads to selection. This process can be considered a large scale, in vivo screen for mutations increasing cell fitness. It follows that somatic missense mutations may offer new insights into the relationship between protein structure, function and cell fitness. We present a flexible statistical method for exploring the selection of structural features in data sets of somatic mutants. We show how this approach can evidence selection of specific structural features in key drivers in aged tissues. Finally, we show how drivers may be classified as fitness-enhancing and fitness-suppressing through different patterns of mutation enrichment. This method offers a route to understanding the mechanism of protein function through in vivo mutant selection.
| Type: | Article |
|---|---|
| Title: | Mutations observed in somatic evolution reveal underlying gene mechanisms |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s42003-023-05136-y |
| Publisher version: | https://doi.org/10.1038/s42003-023-05136-y |
| Language: | English |
| Additional information: | 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10173224 |
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