Microorganisms 2021, 9, 2409. https://doi.org/10.3390/microorganisms9112409 www.mdpi.com/journal/microorganisms Article Leishmania and the Model of Predominant Clonal Evolution Michel Tibayrenc 1, * and Francisco J. Ayala 2 1 Maladies Infectieuses et Vecteurs Ecologie, Génétique, Evolution et Contrôle, MIVEGEC (IRD 224-CNRS 5290-UM1-UM2), Institut de Recherche Pour le Développement, CEDEX 5, 34394 Montpellier, France 2 Catedra Francisco Jose Ayala of Science, Technology, and Religion, University of Comillas, 28015 Madrid, Spain; Fjayala2018@gmail.com * Correspondence: michel.tibayrenc@ird.fr Abstract: As it is the case for other pathogenic microorganisms, the respective impact of clonality and genetic exchange on Leishmania natural populations has been the object of lively debates since the early 1980s. The predominant clonal evolution (PCE) model states that genetic exchange in these parasites’ natural populations may have a high relevance on an evolutionary scale, but is not suffi- cient to erase a persistent phylogenetic signal and the existence of bifurcating trees. Recent data based on high-resolution markers and genomic polymorphisms fully confirm the PCE model down to a microevolutionary level. Keywords: evolution; clonality; genetic recombination; population structure; aneuploidy; molecular epidemiology; parasite; leishmaniosis 1. Introduction The “clonality/sexuality debate” has been running among microbiologists since the early 1980s [1–3], thanks to the advent of reliable genetic markers, such as Multilocus En- zyme Electrophoresis* (MLEE). The issue is relevant for basic science (knowledge on the basic biology of the concerned pathogens), as well as for applied research (strain typing, epidemiological follow-up). As a matter of fact, if the concerned species is sexual (= re- combining*), its multilocus genotypes* (MLGs) are unstable and vanish in the common gene pool after each recombination episode. On the other hand, if the species is clonal, recombination does not operate, and the MLGs of the species under study are stable in space and time. In the framework of this debate, we have proposed “the clonal theory of parasitic protozoa” [4], which has been afterwards extended to other eukaryotic pathogens, then to bacteria and viruses [5]. We present here the most recent developments of this theory dealing with the Leish- mania genus. 2. A Brief Recall on the Clonal Theory in Its Present Form: The Predominant Clonal Evolution Model (PCE) Since its early developments, we have always given the same meaning to clonality: restrictions to genetic recombination impacting the population structure of the species under study. The definition, therefore, deals with the actual effects of clonality on popu- lation structure, and neither on cytological aspects of sex, nor on specific mating patterns. This definition of clonality is accepted by many, if not most, authors working on microbial biology (see for extensive references [5–7,8]), and on clonal metazoa [9]. Some authors do not accept this definition of clonality, and recommend distinguishing selfing/inbreeding from “true” clonality (= mitotic propagation) [9]. Other authors equate clonality with ge- netic monomorphism [10]. Citation: Tibayrenc, M.; Ayala, F.J. Leishmania and the Model of Predominant Clonal Evolution. Microorganisms 2021, 9, 2409. https://doi.org/10.3390/ microorganisms9112409 Academic Editor: Gabriele Schönian Received: 1 November 2021 Accepted: 20 November 2021 Published: 22 November 2021 Publisher’s Note: MDPI stays neu- tral with regard to jurisdictional claims in published maps and institu- tional affiliations. Copyright: © 2021 by the authors. Li- censee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and con- ditions of the Creative Commons At- tribution (CC BY) license (https://cre- ativecommons.org/licenses/by/4.0/).