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Previous comparative analysis revealed conservation in genome composition, gene content, and gene organization among <jats:italic>Cryptosporidium<\/jats:italic> spp., with a progressive reductive evolution in metabolic pathways and invasion-related proteins. In this study, we sequenced the genome of zoonotic pathogen <jats:italic>Cryptosporidium felis<\/jats:italic> and conducted a comparative genomic analysis. While most intestinal <jats:italic>Cryptosporidium<\/jats:italic> species have similar genomic characteristics and almost complete genome synteny, fewer protein-coding genes and some sequence inversions and translocations were found in the <jats:italic>C. felis<\/jats:italic> genome. The <jats:italic>C. felis<\/jats:italic> genome exhibits much higher GC content (39.6\u200a%) than other <jats:italic>Cryptosporidium<\/jats:italic> species (24.3\u201332.9\u200a%), especially at the third codon position (GC3) of protein-coding genes. Thus, <jats:italic>C. felis<\/jats:italic> has a different codon usage, which increases the use of less energy costly amino acids (Gly and Ala) encoded by GC-rich codons. While the tRNA usage is conserved among <jats:italic>Cryptosporidium<\/jats:italic> species, consistent with its higher GC content, <jats:italic>C. felis<\/jats:italic> uses a unique tRNA for GTG for valine instead of GTA in other <jats:italic>Cryptosporidium<\/jats:italic> species. Both mutational pressures and natural selection are associated with the evolution of the codon usage in <jats:italic>Cryptosporidium<\/jats:italic> spp., while natural selection seems to drive the codon usage in <jats:italic>C. felis<\/jats:italic>. Other unique features of the <jats:italic>C. felis<\/jats:italic> genome include the loss of the entire traditional and alternative electron transport systems and several invasion-related proteins. Thus, the preference for the use of some less energy costly amino acids in <jats:italic>C. felis<\/jats:italic> may lead to a more harmonious parasite\u2013host interaction, and the strengthened host-adaptation is reflected by the further reductive evolution of metabolism and host invasion-related proteins.<\/jats:p>","DOI":"10.1099\/mgen.0.000711","type":"journal-article","created":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T13:17:43Z","timestamp":1639574263000},"source":"Crossref","is-referenced-by-count":2,"title":["Cryptosporidium felis differs from other Cryptosporidium spp. in codon usage"],"prefix":"10.1099","volume":"7","author":[{"given":"Jiayu","family":"Li","sequence":"first","affiliation":[{"name":"Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, PR China"},{"name":"Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR 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