Applying evolutionary genetics to schistosome epidemiology

Abstract

We review how molecular markers and evolutionary analysis have been applied to the study of schistosome parasites, important pathogens that infect over 200 million people worldwide. Topics reviewed include phylogenetics and biogeography, hybridization, infection within snails, mating systems, and genetic structure. Some interesting generalizations include that schistosome species hybridize frequently and have switched definitive hosts repeatedly in evolutionary time. We show that molecular markers can be used to infer epidemiologically relevant processes such as spatial variation in transmission, or to reveal complex patterns of mate choice. Analysis of genetic structure data shows that transmission foci can be structured by watershed boundaries, habitat types, and host species. We also discuss sampling and analytical problems that arise when using larvae to estimate genetic parameters of adult schistosome populations. Finally, we review pitfalls in methodologies such as genotyping very small individuals, statistical methods for identifying clonemates or for identifying sibling groups, and estimating allele frequencies from pooled egg samples.

Figure 1

Life cycle of schistosome parasites. Each generation undergoes sexual reproduction (obligate outcrossing) in a mammal host and asexual reproduction within a snail host. Adult worms reproduce sexually in the veins (mesenteric or bladder plexus) of their mammal host and excrete eggs that are eliminated with feces or urine of the host. Eggs hatch in freshwater and release a free swimming miracidium. The miracidium penetrates a snail host, develops into a sporocyst and undergoes several rounds of asexual reproduction that result in the generation of numerous cercariae that emerge from the snail, enter the water, and penetrate the skin of their mammal host. Thus, it is possible for mammal hosts to obtain multiple individuals that are essentially genetically identical or “clones”.

Figure 2

An example of the family structure present in a sample of miracidia from a fecal sample. Adult males and females mate and produce offspring which are related to each other as full siblings. If the males shaded black are clonemates and each mates with a different female, then the two sibships will be related as paternal half siblings.

Figure 3

Sources of sampling variance that can lead to apparent genetic structure among hosts (infrapopulations), or among component populations (e.g. geographic locations) if few hosts are sampled per component population. Each generation, eggs are passed into the environment and the resulting larvae randomly re-infect hosts creating an essentially random mating component population (cf Criscione and Blouin, 2006). Reproducing adults (breeders) are subdivided into definitive host infrapopulations of say N breeders per host. If one were to measure the allele frequencies of the infrapopulations, the variance in allele frequencies among them would be V_p = p(1−p)/2N, where p is the frequency of the allele in the component population. In this example, p1–p3 are the allele frequencies in the adults in each infrapopulation. p1′ – p3′ are the allele frequencies in samples of the offspring of those adults (eggs or miracidia). The variance among offspring samples, V_p′, is now calculated by replacing N with the effective number of breeders per host, N_b. Because N_b is typically much smaller than N, the variance among offspring samples can be much greater than the variance among infrapopulation samples (V_p′ > V_p). Thus, when sampling offspring, a small N_b could cause one to conclude that there is large differentiation among infrapopulations, even though the adults were sampled from a panmictic population. If few infrapopulations are sampled per component population, F_st could be inflated among component populations. Passing miracidia through snails and mice and then genotyping adults could add additional components of variance owing to drift and to host-induced selection among parasite families.