We propose that clonal evolution in micropathogens be defined as restrained recombination on an evolutionary scale, with genetic exchange scarce enough to not break the prevalent pattern of clonal population structure, a definition already widely used for all kinds of pathogens, although not clearly formulated by many scientists and rejected by others. The two main manifestations of clonal evolution are strong linkage disequilibrium (LD) and widespread genetic clustering ("near-clading"). We hypothesize that this pattern is not mainly due to natural selection, but originates chiefly from in-built genetic properties of pathogens, which could be ancestral and could function as alternative allelic systems to recombination genes ("clonality/sexuality machinery") to escape recombinational load. The clonal framework of species of pathogens should be ascertained before any analysis of biomedical phenotypes (phylogenetic character mapping). In our opinion, this model provides a conceptual framework for the population genetics of any micropathogen. molecular epidemiology | infectious disease | selfing I n the last two decades, the population genetics and evolution of pathogens have received much deserved attention. Impressive progress has been achieved through the development of wholegenome sequencing (WGS), bioinformatics, and other powerful molecular technologies. This progress has made it possible to explore, in depth, the central question of genetic exchange in pathogens, the issue of clonality vs. sexuality, which emerged in the 1980s, both in parasitic protozoa (the "clonal theory of parasitic protozoa") (1-3) and in bacteria (4-6). We seek to update the terms and interpretations of the controversy. Compartmentalization among researchers working on different pathogens has resulted in misinterpretations, semantic confusion, and different methods of analysis that often reflect idiosyncratic practices among different scientific communities, rather than distinctive evolutionary features.We analyze population genetic data for bacteria (48 species) (4-82), fungi and yeasts (9 species) (83-93), parasitic protozoa (21 species) (1-3, 94-162), and viruses (11 species or categories) (163-188) (Table S1). There are striking evolutionary similarities among different kinds of pathogens, which are obscured by compartmentalization. We propose ways of consolidating the different approaches and of exploring whether similar evolutionary strategies represent ancestral characters or convergent evolution. We summarize the implications for applied research (including taxonomy, molecular epidemiology, medical characters, and experimental evolution).
Definition of Clonal Evolution: Restricted Genetic RecombinationIn our early papers dealing with the clonality/sexuality issue in parasitic protozoa and fungi (1-3), we advanced an unambiguous definition of clonality/clonal evolution. It did not refer to the cytological mechanism of reproduction, but rather to the population structure that results from an absence or restriction of genetic reco...