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To understand the genetic basis for host adaptation, we sequenced the genomes of <jats:italic>C. canis<\/jats:italic> from dogs, minks, and foxes and conducted a comparative genomics analysis. While the genomes of <jats:italic>C. canis<\/jats:italic> have similar gene contents and organisations, they (~41.0\u200a%) and <jats:italic>C. felis<\/jats:italic> (39.6\u200a%) have GC content much higher than other <jats:italic>Cryptosporidium<\/jats:italic> spp. (24.3\u201332.9\u200a%) sequenced to date. The high GC content is mostly restricted to subtelomeric regions of the eight chromosomes. Most of these GC-balanced genes encode <jats:italic>Cryptosporidium-<\/jats:italic>specific proteins that have intrinsically disordered regions and are involved in host-parasite interactions. Natural selection appears to play a more important role in the evolution of codon usage in GC-balanced <jats:italic>C. canis<\/jats:italic>, and most of the GC-balanced genes have undergone positive selection. While the identity in whole genome sequences between the mink- and dog-derived isolates is 99.9\u200a% (9365 SNVs), it is only 96.0\u200a% (362\u200a894 SNVs) between them and the fox-derived isolate. In agreement with this, the fox-derived isolate possesses more subtelomeric genes encoding invasion-related protein families. Therefore, the change in subtelomeric GC content appears to be responsible for the more GC-balanced <jats:italic>C. canis<\/jats:italic> genomes, and the fox-derived isolate could represent a new <jats:italic>Cryptosporidium<\/jats:italic> species.<\/jats:p>","DOI":"10.1099\/mgen.0.001052","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T16:16:11Z","timestamp":1688400971000},"source":"Crossref","is-referenced-by-count":2,"title":["High subtelomeric GC content in the genome of a zoonotic Cryptosporidium species"],"prefix":"10.1099","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9449-8668","authenticated-orcid":false,"given":"Jiayu","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, PR 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