H2020Индивидуална стипендия2022–2024

EGR · The role of genetic redundancy in adaptive evolution of efflux pumps

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2022-09-01 → 2024-08-31
Финансиране от ЕС: 191 149 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Генетичното дублиране при бактериите се изучава чрез протеини, наречени ефлуксни помпи, които изхвърлят антибиотици от клетката. Разбирането на този механизъм помага да се разбере защо бактериите остават устойчиви на лекарства, дори когато някои от техните гени липсват.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

The role of genetic redundancy in adaptive evolution of efflux pumps

This project addresses the broad problem of genetic redundancy and its role in evolution. Genetic redundancy refers to the fact that multiple genes in a genome can carry out similar or identical functions. Because these genes can substitute each other functionally, the loss of some genes often has no apparent effect on biological fitness. Despite this, genetic redundancy is widespread across many organisms, including bacteria, suggesting that having redundant genes is advantageous even for species with relatively small genomes. This raises fundamental questions: why have functionally replaceable genes persisted for long evolutionary time, and is genetic redundancy evolutionarily advantageous? To address these questions, we employed gene editing, deep sequencing, and computational analysis. We focused on genes encoding multidrug resistance efflux pumps. Efflux pumps are membrane proteins that actively export specific chemicals, including antibiotics, out of cells. The efflux of antibiotics is one of the major mechanisms allowing pathogenic bacteria to resist antibiotic exposure and leading to treatment failure. Most pathogenic bacteria have multiple multidrug resistance efflux pumps, representing five protein families with distinct structures and mechanisms yet overlapping activities against antibiotics. This makes efflux pumps a good model to study genetic redundancy.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

In genetic redundancy, multiple genes in a genome perform the same or similar function. Although redundancy is widespread across the tree of life, its evolutionary origins are not entirely understood. Genetic redundancy may provide a fitness benefit during evolution by increasing gene dosage and protecting critical genes from deleterious mutations. These fitness effects have been confirmed experimentally, but their long-term consequences for evolution have not been tested. In this study, I will manipulate the genomic content of efflux pump genes in E. coli and test the effect of their redundancy using directed evolution of proteins. By evolving the multidrug efflux pump AcrAB at different levels of redundancy, I will determine how the presence of other genes with overlapping drug-efflux activities affects adaptive evolution. I will compare evolutionary trajectories using comprehensive sequence and fitness analysis of the evolved efflux pump variants. This approach will provide a unique opportunity to directly test the role of genetic redundancy in evolution and help to understand why genetic redundancy is maintained in a genome.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITAT ZURICH · ZurichКоординаторШвейцария