Recent transcontinental sweep of Toxoplasma gondii driven by a single monomorphic chromosome

Abstract

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 approximately 10(6) 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.

Fig. 1.

T. gondii strains show marked geographic separation and clonality. (A) Phylogenetic analysis of T. gondii strains based on intron sequences identified 11 separate haplogroups (numbered in boxes), with striking geographic separation between NA and E (blue lettering) and SA (red lettering). Unrooted phylogram generated by using neighbor-joining analysis; bootstrap values are given by the percent at each node. (B) Diagram of the MRCA for strains of T. gondii (SI Table 5). The major North–South split occurred ≈10⁶ yr ago; group 11 (COUG) precedes this split. The emergence of a monomorphic Chr1 in both NA/E and SA strains was ≈10,000 yr ago (small yellow circle). Phenotypic traits for oral transmission (ORAL) and acute virulence (VIR) are as described in SI Table 2.

Fig. 2.

Structure of T. gondii populations. (A) Analysis of present-day haplogroups using K = 4 populations identified 11 groups, corresponding to the haplogroups defined in Fig. 1. (B) Model for generation of current haplogroups by admixture of ancient groups resembling 2, 4, 6, and 9. WW, worldwide distribution.

Fig. 3.

Sequence divergence of ChrIa among strains of T. gondii. (A) Numbered regions (8) were sequenced from each of the stains shown. Mono-ChrIa (white) indicates identical. Alternative (red) indicates a separate shared allele. Divergent (blue) indicates highly distinct alleles. Mixed (green) represents recombinant regions. MonoChr1a* (gray) indicates minor variants (i.e., single SNP). Yellow regions are not sequenced. (B) Network analysis of apicoplast inheritance among select strains of T. gondii. Haplogroups with shared maternal inheritance typically also contained mono-ChrIa (yellow shading), whereas strains with divergent ChrIa (blue) fall on separate nodes of the network.

Fig. 4.

Proposed model for the dissemination of T. gondii strains in E, NA, and SA. The spread from NA to SA is estimated at 10⁶ yr (curved blue arrow). Emergence of Mono-Chr1a occurred ≈10,000 yr ago (horizontal yellow arrow) and spread between NA and E. More recently, Mono-Chr1a penetrated into SA (curved yellow arrow). The outer color wheels show the prevalence of haplogroups in current populations; the inner color wheel depicts ChrIa. Strains used include those studied here plus previously isolated strains (2, 12, 19, 27).