Assembled chromosomes of the blood fluke Schistosoma mansoni provide insight into the evolution of its ZW sex-determination system

Abstract

Background: Schistosoma mansoni is a flatworm that causes a neglected tropical disease affecting millions worldwide. Most flatworms are hermaphrodites but schistosomes have genotypically determined male (ZZ) and female (ZW) sexes. Sex is essential for pathology and transmission, however, the molecular determinants of sex remain unknown and is limited by poorly resolved sex chromosomes in previous genome assemblies. Results: We assembled the 391.4 Mb S. mansoni genome into individual, single-scaffold chromosomes, including Z and W. Manual curation resulted in a vastly improved gene annotation, resolved gene and repeat arrays, trans-splicing, and almost all UTRs. The sex chromosomes each comprise pseudoautosomal regions and single sex-specific regions. The Z-specific region contains 932 genes, but on W all but 29 of these genes have been lost and the presence of five pseudogenes indicates that degeneration of W is ongoing. Synteny analysis reveals an ancient chromosomal fusion corresponding to the oldest part of Z, where only a single gene-encoding the large subunit of pre-mRNA splicing factor U2AF has retained an intact copy on W. The sex-specific copies of U2AF have divergent N-termini and show sex-biased gene expression. Conclusion: Our assembly with fully resolved chromosomes provides evidence of an evolutionary path taken to create the Z and W sex chromosomes of schistosomes. Sex-linked divergence of the single U2AF gene, which has been present in the sex-specific regions longer than any other extant gene with distinct male and female specific copies and expression, may have been a pivotal step in the evolution of gonorchorism and genotypic sex determination of schistosomes.

Chromosome-level genome of Schistosoma haematobium underpins genome-wide explorations of molecular variation

“…194) of Shae.V3 suggests that this scaffold represents a female-specific portion of the W chromosome. However, the complete Wspecific region (WSR) is likely much larger based on evidence for S. mansoni, whose highlyrepetitive WSR is estimated at 18-46 Mb [39]. Future work is warranted to fully resolve the sex chromosomes of S. haematobium using long-read data from individual worms (females and males) as a foundation for detailed explorations of sex-determining genes and sex-and developmentally-regulated gene expression.…”

Improving helminth genome resources in the post-genomic era

“…Addressing these two points has been the focus of research efforts for a limited number of helminth species, which have seen iterative improvement in the genomic resources over time from fragmented draft assemblies to chromosome-scale and reference-quality assemblies (Figure 2). These improvements have led to fundamental new insights into parasite biology that could not have been addressed using a draft genome, including the resolution of drug resistance QTL in Haemonchus contortus [42,43], the evolution of sex chromosomes of Brugia malayi (and related filarial species) [44] and delineation of separate Z and W sex chromosomes of Schistosoma mansoni [45], and the unusual centromere and telomere structures found at the ends of chromosomes in Hymenolepis microstoma [46].…”

“…o Examples: S. mansoni [45], Schistosoma japonicum [51], Schistosoma haematobium [52], Hymenolepis microstoma [46], H. contortus [14], B. malayi/Dirofilaria immitis [53], Heterodera glycines [54], Clonorchis sinensis [55], Ascaris suum [56], Oscheius tipulae [57], P. pacificus [58], Nector americanus [59]. • Community annotation o Engaging school-age/undergraduate students [60].…”

Daily rhythms in gene expression of the human parasite Schistosoma mansoni

“…There were also sex differences in the diel genes involved in the nightly chaperone response. For example, a DNAj (hsp40), which has homologues located on the different sex chromosomes (known as gametologues) [27], has diel expression in both gametologues. Schistosomes have a ZW sex chromosome system, where females are ZW and males are ZZ.…”