Mobile genetic element contribution to the genome architecture of the human parasitic flatworm Schistosoma mansoni

Schistosomiasis is a parasitic disease that affects approximately 250 million individuals worldwide, resulting in an estimated loss of more than 20 million disability-adjusted life years. Around 700 million people, predominantly in developing countries, live in at-risk areas. Schistosomiasis is caused by trematodes of the Schistosoma genus, with Schistosoma mansoni being the best characterised species and responsible for a significant proportion of deaths. S. mansoni has a complex life cycle involving two free living aquatic stages, a definitive human host and intermediate snail host. Its genome is repeat-rich, with transposable elements (TEs) comprising approximately 35% and Schistosoma-specific W elements (WEs) an additional 10%. Repetitive elements have a profound impact on host genomes, directly contributing to protein-coding genes via transposition in a process known as exaptation and stimulating recombination, particularly between subtelomeres. These regions are repeat-rich, prone to repeat element-mediated recombination and, in other organisms, harbour genes associated with parasite proliferation, invasion, and survival. Horizontal transfer of TEs is especially impactful, as periods of increased transposition are commonly observed post-acquisition, which may impact the genome, contributing to phenomena such as exaptation or the repeat-richness of the subtelomere. These events also provide insight into an organism’s evolutionary history. I aimed to characterise the origins and contribution of repetitive elements to the S. mansoni genome, leveraging newly available genomic resources. I identify two putatively horizontally transferred elements in the S. mansoni genome, that were detected in Schistosoma intermediate hosts but not closer related trematodes, most likely explained by HGT. Additionally, Perere-3 / Sr3 were found in a diverse range of organisms not susceptible to schistosome infection, including turtles, fish and other molluscs. I demonstrate the substantial contribution of repetitive elements to S. mansoni genes, including evidence of a potential instance of exaptation. Finally, I leveraged the repeat richness identified at S. mansoni chromosome termini to define and characterise the subtelomere, revealing extensive interchromosomal recombination. This recombination has driven the expansion of subtelomere gene clusters, including those encoding immunomodulatory proteins and other proteins potentially involved in host-parasite interactions. These findings highlight the profound impact of TEs, both those horizontally and vertically acquired, on the S. mansoni genome, shaping both its structure and function.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2024

Author dc:creator

• Brann, Toby

Advisor dc:contributor.advisor

• Boemo, Michael

• schistosoma
• transposable element
• transposon
• mansoni
• subtelomere
• recombination

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/7d5d6ca3-a0bc-455b-a76c-43386b15752d/download
• http://purl.org/NET/rdflicense/allrightsreserved

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.117826

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/383479