title: Integrated mapping, chromosomal sequencing and sequence analysis of Cryptosporidium parvum.
abstract: The apicomplexan Cryptosporidium parvum is one of the most prevalent protozoan parasites of humans. We report the physical mapping of the genome of the Iowa isolate, sequencing and analysis of chromosome 6, and approximately 0.9 Mbp of sequence sampled from the remainder of the genome. To construct a robust physical map, we devised a novel and general strategy, enabling accurate placement of clones regardless of clone artefacts. Analysis reveals a compact genome, unusually rich in membrane proteins. As in Plasmodium falciparum, the mean size of the predicted proteins is larger than that in other sequenced eukaryotes. We find several predicted proteins of interest as potential therapeutic targets, including one exhibiting similarity to the chloroquine resistance protein of Plasmodium. Coding sequence analysis argues against the conventional phylogenetic position of Cryptosporidium and supports an earlier suggestion that this genus arose from an early branching within the Apicomplexa. In agreement with this, we find no significant synteny and surprisingly little protein similarity with Plasmodium. Finally, we find two unusual and abundant repeats throughout the genome. Among sequenced genomes, one motif is abundant only in C. parvum, whereas the other is shared with (but has previously gone unnoticed in) all known genomes of the Coccidia and Haemosporida. These motifs appear to be unique in their structure, distribution and sequences.
authors.affiliation: Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB 2 2QH, UK.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Bankier
authors.forename: Helen F
authors.initials: HF
authors.lastname: Spriggs
authors.forename: Berthold
authors.initials: B
authors.lastname: Fartmann
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Konfortov
authors.forename: Martin
authors.initials: M
authors.lastname: Madera
authors.forename: Christine
authors.initials: C
authors.lastname: Vogel
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Teichmann
authors.forename: Al
authors.initials: A
authors.lastname: Ivens
authors.forename: Paul H
authors.initials: PH
authors.lastname: Dear
mesh_terms: D000818:Animals; D001482:Base Composition / Q000235:genetics; D002503:Centromere / Q000235:genetics; D003457:Cryptosporidiosis / Q000175:diagnosis / Q000382:microbiology / Q000628:therapy; D016785:Cryptosporidium parvum / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D016054:DNA, Protozoan / Q000032:analysis; D018628:Gene Dosage; D015316:Genetic Therapy; D018503:Genome, Protozoan; D008969:Molecular Sequence Data; D010802:Phylogeny; D020161:Physical Chromosome Mapping / Q000379:methods*; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*; D020080:Tandem Repeat Sequences / Q000235:genetics; D016615:Telomere / Q000235:genetics
chemical_list: D016054:DNA, Protozoan