Genomes and geography: genomic insights into the evolution and phylogeography of the genus Schistosoma

Abstract

Blood flukes within the genus Schistosoma still remain a major cause of disease in the tropics and subtropics and the study of their evolution has been an area of major debate and research. With the advent of modern molecular and genomic approaches deeper insights have been attained not only into the divergence and speciation of these worms, but also into the historic movement of these parasites from Asia into Africa, via migration and dispersal of definitive and snail intermediate hosts. This movement was subsequently followed by a radiation of Schistosoma species giving rise to the S. mansoni and S. haematobium groups, as well as the S. indicum group that reinvaded Asia. Each of these major evolutionary events has been marked by distinct changes in genomic structure evident in differences in mitochondrial gene order and nuclear chromosomal architecture between the species associated with Asia and Africa. Data from DNA sequencing, comparative molecular genomics and karyotyping are indicative of major constitutional genomic events which would have become fixed in the ancestral populations of these worms. Here we examine how modern genomic techniques may give a more in depth understanding of the evolution of schistosomes and highlight the complexity of speciation and divergence in this group.

Figure 1

Maps displaying the two hypotheses of the origins of the schistosomes. 1a showing the African origin as suggested by Davis [2,3] 1) and 2) indicate the African Schistosoma moving over to Asia on the Indian plate 70-148 MYA, giving rise to the S. indicum group and diversifying into the S. japonicum group. 3) and 4) suggest the Schistosoma ancestor remaining in Africa diverged > 120 MYA, giving rise to the S. mansoni and S. haematobium groups. 1b showing the Asian origin as put forward by Rollinson et al. [6], Snyder and Loker [13]: 1) S. japonicum-like ancestor arises and diversifies in Asia. 2) Asian descendents of the ancestral schistosome move into Africa with the widespread mammal migration between 12-19 MYA. 3) and 4) the African schistosome diverges 1-4 MYA, giving rise to the S. mansoni and S. haematobium groups. At this time, the ancestors of the S. indicum group emerge and move to India again via the mass movement of large mammals (Figure adapted from [5]).

Figure 2

Summary schematic phylogeny of the interrelationships of members of the species within the Schistosoma genus estimated with a Bayesian analysis of combined partial lsrDNA, complete ssrDNA and partial cox1. Nodal support indicated as posterior probabilities and bootstrap percentages (n = 2000) from maximum parsimony analysis. This tree also indicates the four main clades and the two referred to in this study, which in the past have been classified on their egg morphology and both intermediate and definitive hosts: the S. japonicum group (S. sinensium, S. ovuncatum (inferred from partial lsrDNA) S. japonicum, S. malayensis, S. mekongi) being basal to the Schistosoma group, and the S. mansoni group (S. mansoni, S. rodhaini) being the first major split in the African clades, with the S. indicum group (S. nasale, S. spindale, S indicum) and the S. haematobium group (S. margrebowiei, S. leiperi, S. mattheei, S. intercalatum, S. kisumuensis, S. haematobium, S. guineensis, S. curassoni and S. bovis). The tree also illustrates the basal nature of Asian schistosomes, being ancestral to the African stock due to the relative positions of S. hippopotami, S. edwardiense (Inferred from partial cox1), Orientobilharzia and S. incognitum. (Adapted from [8-10])

Figure 3

Gene order rearrangements within the Schistosoma mitochondrial genome. The Asian schistosomes from the S. japonicum complex appear to have retained the general digenean gene order in their mitochondrial genomes when compared to other flukes such as Fasciola and Paragonimus. However, major gene order changes in the African clades (S. mansoni and S. haematobium) and the S. indicum group are apparent. The phylogeny is a maximum likelihood tree estimated from complete 18S rDNA and gene order rearrangements in mitochondrial genomes provide characters for estimating positions on the phylogeny. Where the cytochrome oxidase genes are cox1, cox2, cox3; NADH dehydrogenase genes are nad1, nad2, nad3, nad4, nad4L, nad5, nad6; ATP synthase gene is atp6, cytochrome b gene is cob, rrnL is 16s, rrnS is 12s SNR, is the short noncoding region and the circles represent tRNAs (Adapted from [22-24]).

Figure 4

Two models on the evolution of sex chromosomes of the schistosomatids. A) Short and Grossman's (1981, 1983) Ideograms proposing the evolution of the sex chromosomes to have followed a similar trend to the rest of the genome, arising from a hermaphrodite ancestor. Two homologous chromosomes that contained the genes for sex determination began to diverge as a result of reduced recombination and gave rise to the ancestors of each schistosomatid group independently. B) Based on the mtDNA data and morphology of the chromosomes, a plausible model of sex chromosome evolution can be put forward suggesting that heterochromatinization events are the major factor in the differentiation of the sex chromosomes in the schistosomatids but also that the pattern of morphological differentiation shows the same relationship as the mitochondrial genome data.

Figure 5

Semi-schematic summarizing a phylogeography and genome evolution of Schistosoma with respect to the evolutionary biogeography of the parasites showing that the genus arose in Central Asia in rodents during the Miocene. The S. japonicum lineage radiates in rodents in China and Southeast Asia. Orientobilharzia acquires artiodactyls as hosts in Central Asia sharing homology with an ancestor that enters Africa during the late Miocene and gives rise to the S. haematobium and S. mansoni lineages. The Pliocene large mammal radiation in Africa triggers the divergence of several lineages of Schistosoma utilizing Artiodactyla. The Plio-Pleistocene large mammal divergence into Asia and the emergence of Bovidae then drives the divergence of the Schistosoma indicum lineage from one of the African artiodactyle Schistosoma clades. Schistosoma of bovids establish on the Indian subcontinent and in Southeast Asia but apparently less so in Central Asia. In Southeast Asia, both S. incognitum and S. spindale undergo near isochronous colonization and radiation from India. The schematic indicates the evolutionary signals that have been produced by genomic data to provide the evidence of the Asian origin of the schistosomes. The ancestor of the African schistosomes shared homology with Orientobilharzia and S. incognitum and a genetic bottleneck occurred, as indicated by the reduction in size of the sex chromosomes and fixed the mt genome rearrangement as the schistosomes moved into Africa. The African schistosomes evolved from a S. mansoni-like ancestor with all African parasites showing the same gene order in the mt genome and all showing karyotypes to be derived from the S. mansoni type, a trend also seen in the S. indicum group as it reinvaded Asia (Adapted from [1]).