Chromosome‐level genome assembly defines female‐biased genes associated with sex determination and differentiation in the human blood fluke Schistosoma japonicum

Abstract

Schistosomiasis is a neglected tropical disease of humans caused by blood flukes of the genus Schistosoma, the only dioecious parasitic flatworm. Although aspects of sex determination, differentiation and reproduction have been studied in some Schistosoma species, almost nothing is known for Schistosoma japonicum, the causative agent of schistosomiasis japonica. This mainly reflects the lack of high‐quality genomic and transcriptomic resources for this species. As current genomes for S. japonicum are highly fragmented, we assembled and report a chromosome‐level reference genome (seven autosomes, the Z‐chromosome and partial W‐chromosome), achieving a substantially enhanced gene annotation. Utilizing this genome, we discovered that the sex chromosomes of S. japonicum and its congener S. mansoni independently suppressed recombination during evolution, forming five and two evolutionary strata, respectively. By exploring the W‐chromosome and sex‐specific transcriptomes, we identified 35 W‐linked genes and 257 female‐preferentially transcribed genes (FTGs) from our chromosomal assembly and uncovered a signature for sex determination and differentiation in S. japonicum. These FTGs clustering within autosomes or the Z‐chromosome exhibit a highly dynamic transcription profile during the pairing of female and male schistosomula, thereby representing a critical phase for the maturation of the female worms and suggesting distinct layers of regulatory control of gene transcription at this development stage. Collectively, these data provide a valuable resource for further functional genomic characterization of S. japonicum, shed light on the evolution of sex chromosomes in this highly virulent human blood fluke, and provide a pathway to identify novel targets for development of intervention tools against schistosomiasis.

Evidence of a Slower-Z effect inSchistosoma japonicum

“…Elkrewi et al (2021) and Xu et al (2023) recently described evolutionary strata of different ages along the Z chromosome of S. japonicum , and in particular the presence of a large section of the ZW pair that no longer recombines, but still exists on the W. However, a highly fragmented genome was used in Elkrewi et al (2021), and no population genomics data was used to infer young non-recombining regions in Xu et al (2023). We therefore set out to define precise boundaries of the diploid and hemizygous Z regions on the published chromosome-level assembly of S. japonicum (Luo et al, 2022).…”

“…We therefore set out to define precise boundaries of the diploid and hemizygous Z regions on the published chromosome-level assembly of S. japonicum (Luo et al, 2022). Using both coverage patterns and genetic differentiation between a population of males and females, we recovered large contiguous hemizygous and non-recombining but diploid Z regions (Xu et al, 2023, Elkrewi et al 2021) ( Figure 1 ). In particular, a large region where female coverage is consistently half of male coverage is consistent with the degeneration of the homologous region of the W chromosome, i.e.…”

“…While they all share an ancestral pair of ZW chromosomes, the non-recombining part of the sex chromosomes has been expanded independently in different lineages (Picard et al, 2018). A very young non-recombining region of the Z chromosome has been recently identified in the Asian species Schistosoma japonicum (Elkrewi et al 2021, Xu et al, 2023). This region has over 700 functional W genes (ZW dS < 0.085), which makes the corresponding Z region diploid but non-recombining in females.…”

Characterizing genetic variation on the Z chromosome in Schistosoma japonicum reveals host-parasite co-evolution

“…According to the latest genome assembly (SM_V10) of S. mansoni [ 22 ], the Z chromosome contributes ~ 22.1%. For S. japonicum [ 23 ], this contribution is estimated at 21.4%, while for Schistosoma haematobium [ 24 ], it is about 22.3% (with a mixed ZW assembly). Schistosoma bovis and S. mekongi exhibit contributions of 21.6% and 22.8%, respectively [ 25 , 26 ].…”

Chromosome-scale genome of the human blood fluke Schistosoma mekongi and its implications for public health

“…Therefore, it is indispensable to find new effective targets (through genomic and proteomic analysis) for accelerating drug discovery and vaccine development [ 16 ]. Recent progress in sequencing technology has disclosed high-quality genome resources for human blood flukes including S. mansoni [ 17 ], S. haematobium [ 18 – 20 ], and S. japonicum [ 14 , 21 , 22 ]. Although the development and morphological features of S. mekongi are similar to those of other blood flukes [ 23 , 24 ], whole-genome information for this species is still lacking, preventing the exploration of the molecular mechanisms underlying the adaptation, evolution, and genetic manipulation of schistosome species.…”