Population genetics of complex life-cycle parasites: an illustration with trematodes Franck Prugnolle a, * , Hua Liu a , Thierry de Meeu ˆs b , Franc ¸ois Balloux a a Theoretical and Molecular Population Genetics Group, Department of Genetics, Cambridge CB2 3EH, England b GEMI, Equipe ESS, UMR CNRS-IRD 2724, IRD de Montpellier, 911 av. Agropolis, BP 64501, 34394 Montpellier cedex 5, France Received 28 July 2004; received in revised form 13 October 2004; accepted 18 October 2004 Abstract Accurate inferences on population genetics data require a sound underlying theoretical null model. Organisms alternating sexual and asexual reproduction during their life-cycle have been largely neglected in theoretical population genetic models, thus limiting the biological interpretation of population genetics parameters measured in natural populations. In this article, we derive the expectations of those parameters for the life-cycle of monoecious trematodes, a group comprising several important human and livestock parasites that obligatorily alternate sexual and asexual reproduction during their life-cycle. We model how migration rates between hosts, sexual and asexual mutation rates, adult selfing rate and the variance in reproductive success of parasites during the clonal phase affect the amount of neutral genetic diversity of the parasite (effective population size) and its apportionment within and between definitive hosts (using F-statistics). We demonstrate, in particular, that variance in reproductive success of clones, a parameter that has been completely overlooked in previous population genetics models, is very important in shaping the distribution of the genetic variability both within and among definitive hosts. Within definitive hosts, the parameter F IS (a measure of the deviation from random mating) is decreased by high variance in clonal reproductive success of larvae but increased by high adult self-fertilisation rates. Both clonal multiplication and selfing have similar effects on between-host genetic differentiation (F ST ). Migration occurring before and after asexual reproduction can have different effects on the patterns of F IS , depending on values of the other parameters such as the mutation rate. While the model applies to any hermaphroditic organism alternating sexual and clonal reproduction (e.g. many plants), the results are specifically discussed in the light of the limited population genetic data on monoecious trematodes available to date and their previous interpretation. We hope that our model will encourage more empirical population genetics studies on monoecious trematodes and other organisms with similar life-cycles. q 2005 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved. Keywords: F-statistics; Complex life-cycle; Asexual reproduction; Self-fertilisation; Effective population size; Trematodes 1. Introduction The study of population genetic structure of living organisms is central to the understanding of micro- evolutionary processes (Nevo et al., 1984; Nadler, 1995). For small organisms and in particular parasites, the analysis of genetic variation at different hierarchical levels is often the only way to investigate natural population parameters such as gene flow, size of reproductive units and breeding strategies (Nadler, 1995). Population genetic structure can also constitute a powerful tool to investigate epidemiologi- cal patterns (Paterson and Viney, 2000). However, interpreting measurements of genetic variation and its distribution in terms of biological parameters such as dispersal/transmission rates, breeding systems or effective population size is often very difficult. Two main reasons can be invoked to explain this difficulty: (i) a multiplicity of causes can explain specific patterns of genetic variation (e.g. heterozygote deficits can be explained by self- fertilisation, preferential mating between kin, Walhund effects, selection) (Hartl and Clark, 1997), (ii) the lack of clear expectations when the organisms under scrutiny display life-cycles that greatly depart from those used in theoretical population genetic models. Parasites with 0020-7519/$30.00 q 2005 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijpara.2004.10.027 International Journal for Parasitology 35 (2005) 255–263 www.parasitology-online.com * Corresponding author. Tel.: C44 1223 332584; fax: C44 1223 333992. E-mail address: fp235@mole.bio.cam.ac.uk (F. Prugnolle).