How do monomorphic bacteria evolve? The *Mycobacterium tuberculosis* complex and the awkward population genetics of extreme clonalityuse asterix (*) to get italics

Christoph Stritt, Sebastien GagneuxPlease use the format "First name initials family name" as in "Marie S. Curie, Niels H. D. Bohr, Albert Einstein, John R. R. Tolkien, Donna T. Strickland"

2023

<p style="text-align: justify;">Exchange of genetic material through sexual reproduction or horizontal gene transfer is ubiquitous in nature. Among the few outliers that rarely recombine and mainly evolve by <em>de novo</em> mutation are a group of deadly bacterial pathogens, including the causative agents of leprosy, plague, typhoid, and tuberculosis. The interplay of evolutionary processes is poorly understood in these organisms. Population genetic methods allowing to infer mutation, recombination, genetic drift, and natural selection make strong assumptions that are difficult to reconcile with clonal reproduction and fully linked genomes consisting mainly of coding regions. In this review, we highlight the challenges of extreme clonality by discussing population genetic inference with the&nbsp;<em>Mycobacterium tuberculosis</em> complex, a group of closely relatedobligate bacterial pathogens of mammals. We show how uncertainties underlying quantitative models and verbal arguments affect previous conclusions about the way these organisms evolve. A question mark remains behind various quantities of applied and theoretical interest, including mutation rates, the interpretation of nonsynonymous polymorphisms, or the role of genetic bottlenecks. Looking ahead, we discuss how new tools for evolutionary simulations, going beyond the traditional Wright-Fisher framework, promise a more rigorous treatment of basic evolutionary processes in clonal bacteria.</p>

https://doi.org/10.5281/zenodo.8042695You should fill this box only if you chose 'All or part of the results presented in this preprint are based on data'. URL must start with http:// or https://

https://doi.org/10.5281/zenodo.8042695You should fill this box only if you chose 'Scripts were used to obtain or analyze the results'. URL must start with http:// or https://

https://doi.org/10.5281/zenodo.8042695You should fill this box only if you chose 'Codes have been used in this study'. URL must start with http:// or https://

clonality, monomorphic bacteria, mutation, recombination, genetic drift, natural selection, simulation

NonePlease indicate the methods that may require specialised expertise during the peer review process (use a comma to separate various required expertises).

Evolutionary Dynamics, Genome Evolution, Molecular Evolution, Population Genetics / Genomics, Reproduction and Sex

Eduardo Rocha [eduardo.rocha@pasteur.fr], Caitlin S. Pepperell [pepperell@wisc.edu], Ruth Hershberg [ruthersh@technion.ac.il], François Balloux [f.balloux@ucl.ac.uk]

e.g. John Doe john@doe.com

No need for them to be recommenders of PCIEvolBiol. Please do not suggest reviewers for whom there might be a conflict of interest. Reviewers are not allowed to review preprints written by close colleagues (with whom they have published in the last four years, with whom they have received joint funding in the last four years, or with whom they are currently writing a manuscript, or submitting a grant proposal), or by family members, friends, or anyone for whom bias might affect the nature of the review - see the code of conduct

2022-12-16 13:41:53

B. Jesse Shapiro

Gonçalo Themudo