Cryptosporidium spp. infect humans and many other animals, with a clade of species that targets intestinal enterocytes and a clade that colonizes the gastric gland. Unlike intestinal species, gastric species are understudied and genomic sequences are currently available from C. muris and C. andersoni. These species cause mild, self-limiting infections, unlike C. proliferans, which induces severe and sometimes fatal disease. To investigate genomic differences underlying this pathology, we sequenced the C. proliferans genome using short- and long-read technology, producing the most complete gastric Cryptosporidium assembly. The genome is intron rich and encodes host invasion genes (e.g., thioredoxin, insulinase/M16-peptidase) near telomeric or subtelomeric regions, which are enriched with G-quadruplex motifs that likely drive protein diversification. Comparative analyses revealed strong synteny among gastric species but only partial synteny with intestinal species. Selective pressure analyses (dN/d S) showed marked differences between C. muris and C. proliferans, potentially explaining their contrasting disease outcomes.
Keywords: Biological sciences; Health sciences; Microbial genomics; Microbiology parasite; Parasitology.
© 2026 The Authors.