title: Comparative genomic analysis reveals occurrence of genetic recombination in virulent Cryptosporidium hominis subtypes and telomeric gene duplications in Cryptosporidium parvum.
abstract: BACKGROUND
  Cryptosporidium hominis is a dominant species for human cryptosporidiosis. Within the species, IbA10G2 is the most virulent subtype responsible for all C. hominis-associated outbreaks in Europe and Australia, and is a dominant outbreak subtype in the United States. In recent yearsIaA28R4 is becoming a major new subtype in the United States. In this study, we sequenced the genomes of two field specimens from each of the two subtypes and conducted a comparative genomic analysis of the obtained sequences with those from the only fully sequenced Cryptosporidium parvum genome.
  
  
  RESULTS
  Altogether, 8.59-9.05 Mb of Cryptosporidium sequences in 45-767 assembled contigs were obtained from the four specimens, representing 94.36-99.47% coverage of the expected genome. These genomes had complete synteny in gene organization and 96.86-97.0% and 99.72-99.83% nucleotide sequence similarities to the published genomes of C. parvum and C. hominis, respectively. Several major insertions and deletions were seen between C. hominis and C. parvum genomes, involving mostly members of multicopy gene families near telomeres. The four C. hominis genomes were highly similar to each other and divergent from the reference IaA25R3 genome in some highly polymorphic regions. Major sequence differences among the four specimens sequenced in this study were in the 5' and 3' ends of chromosome 6 and the gp60 region, largely the result of genetic recombination.
  
  
  CONCLUSIONS
  The sequence similarity among specimens of the two dominant outbreak subtypes and genetic recombination in chromosome 6, especially around the putative virulence determinant gp60 region, suggest that genetic recombination plays a potential role in the emergence of hyper-transmissible C. hominis subtypes. The high sequence conservation between C. parvum and C. hominis genomes and significant differences in copy numbers of MEDLE family secreted proteins and insulinase-like proteases indicate that telomeric gene duplications could potentially contribute to host expansion in C. parvum.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai, 200237, China. guoyaqiong1987@sina.com.|Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA. guoyaqiong1987@sina.com.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA. kht7@cdc.gov.
authors.forename: Kevin
authors.initials: K
authors.lastname: Tang
authors.affiliation: Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA. ioy0@cdc.gov.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Rowe
authors.affiliation: State Key Laboratory of Bioreactor Engineering, School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai, 200237, China. nli@ecust.edu.cn.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA. iyd4@cdc.gov.
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Roellig
authors.affiliation: Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA. wgg9@cdc.gov.
authors.forename: Kristine
authors.initials: K
authors.lastname: Knipe
authors.affiliation: Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA. mff3@cdc.gov.
authors.forename: Michael
authors.initials: M
authors.lastname: Frace
authors.affiliation: Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA. cxy0@cdc.gov.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai, 200237, China. yyfeng@ecust.edu.cn.
authors.forename: Yaoyu
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA. lxiao@cdc.gov.
authors.forename: Lihua
authors.initials: L
authors.lastname: Xiao
mesh_terms: D055028:Comparative Genomic Hybridization; D020451:Contig Mapping; D003457:Cryptosporidiosis / Q000469:parasitology / Q000473:pathology; D003458:Cryptosporidium / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D016785:Cryptosporidium parvum / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D016054:DNA, Protozoan / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism; D005145:Face / Q000469:parasitology; D020440:Gene Duplication; D016678:Genome; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D033661:Oocysts / Q000378:metabolism; D011995:Recombination, Genetic / Q000235:genetics*; D017422:Sequence Analysis, DNA; D016615:Telomere / Q000235:genetics*; D014774:Virulence / Q000235:genetics
chemical_list: D016054:DNA, Protozoan