BIOLOGICAL SCIENCES / POPULATION BIOLOGY
Recent transcontinental sweep of Toxoplasma gondii driven by a single monomorphic chromosome
Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63130; Department of Microbiology, University of Tennessee, Knoxville, TN 37996; Animal Parasitic Disease Laboratory, Animal and Natural Resources Institute, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705; ¶Faculté de Médecine, EA3174, Biological Resource Center for Toxoplasma, 87042 Limoges, France; and ||Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom
Edited by John J. Mekalanos, Harvard Medical School, Boston, MA, and approved August 1, 2007 (received for review March 13, 2007)
Toxoplasma gondii is a highly prevalent protozoan parasite that infects a wide range of animals and threatens human health by contaminating food and water. A markedly limited number of clonal parasite lineages have been recognized as predominating in North American and European populations, whereas strains from South America are comparatively diverse. Here, we show that strains from North America and Europe share distinct genetic polymorphisms that are mutually exclusive from polymorphisms in strains from the south. A striking exception to this geographic segregation is a monomorphic version of one chromosome (Chr1a) that characterizes virtually all northern and many southern isolates. Using a combination of molecular phylogenetic and phenotypic analyses, we conclude that northern and southern parasite populations diverged from a common ancestor in isolation over a period of 106 yr, and that the monomorphic Chr1a has swept each population within the past 10,000 years. Like its definitive feline hosts, T. gondii may have entered South America and diversified there after reestablishment of the Panamanian land bridge. Since then, recombination has been an infrequent but important force in generating new T. gondii genotypes. Genes unique to a monomorphic version of a single parasite chromosome may have facilitated a recent population sweep of a limited number of highly successful T. gondii lineages.
biogeography | evolution | pathogen | transmission | virulence
PNAS, September 11, 2007, vol. 104, no. 37, 14872-14877. OPEN ACCESS ARTICLE.
Approximately 25% of the world’s human population is chronically infected by Toxoplasma gondii, which also parasitizes an exceptionally wide range of warm-blooded vertebrates (1). Its extraordinary prevalence depends on several adaptations for efficient transmission. Cats can excrete >107 environmentally resistant "oocysts" per day during an active infection (1), and these are capable of contaminating food or water. When ingested by intermediate hosts, the parasite differentiates to form tissue cysts containing semidormant parasites (bradyzoites) within muscle tissue and organs (1). The life cycle is completed when cats ingest such bradyzoites. Unlike most related coccidian parasites, bradyzoites of T. gondii are also infectious when ingested by other intermediate hosts (in which sexual recombination and oocyst formation do not occur) (1). Hence, T. gondii is unusual in that infection may propagate through sexual or entirely asexual means.
Although it possesses a meiotic life-cycle phase, T. gondii has a markedly clonal population structure, and three distinct lineages, types I, II, and III, together account for >95% of strains isolated in North America (NA) and Europe (E) (2–4). These three lineages are derived from only a few meiotic crosses among genetically very similar parental strains (5, 6). The limited genetic diversity within each of these lineages indicates they have arisen within the last 10,000 yr (7). When ingested, the bradyzoites of these clonal lineages all efficiently establish infection not only in cats but also in intermediate hosts, such as rodents (7). The broad host range of these clonal strains and their ability to perpetuate asexually among intermediate hosts may account for their disproportionate success and genetic cohesion (7). Strikingly, all three lineages share a nearly monomorphic version of one chromosome, Chr1a (referred to here as Mono-ChrIa), in stark contrast to the genetic variability characterizing all other chromosomes (8). Fixation of Mono-ChrIa in natural populations, despite the fact that this chromosome undergoes normal levels of recombination in experimental crosses (8, 9), is highly unexpected.
Although clonality clearly typifies isolates from NA and E, isolates from South America (SA) exhibit greater genetic diversity. When applied to strains from SA, markers designed to detect DNA polymorphisms in isolates from NA and E reveal patterns resembling mixtures of types I and III with a lower frequency of type II strains (10). Microsatelite analysis suggests four major lineages of T. gondii, two endemic to SA, one endemic in NA/E, and one occupying a global distribution (11). Although such methods detect genetic variation, they do not reveal all polymorphisms present in a given locus and may misclassify other variants due to homoplasy. Recently, intron sequencing has revealed otherwise previously unseen diversity in SA isolates and has demonstrated that they cannot be adequately characterized based solely on polymorphisms that discriminate among clonal lineages endemic to NA and E (12).
Here we establish the population structure of T. gondii by sequencing introns, which are presumed to be selectively neutral, and by examining the distribution and inheritance of Mono-ChrIa. Genetic lineages were also analyzed for traits of virulence and oral infectivity in mice. Our findings reveal both ancient and recent population changes that were shaped by biogeography over the past several million years and much more recently by the adaptive radiation of a small number of highly successful lineages.