Capture-based enrichment of Theileria parva DNA enables full genome assembly of first buffalo-derived strain and reveals exceptional intra-specific genetic diversity.
Author
Palmateer, Nicholas CTretina, Kyle
Orvis, Joshua
Ifeonu, Olukemi O
Crabtree, Jonathan
Drabék, Elliott
Pelle, Roger
Awino, Elias
Gotia, Hanzel T
Munro, James B
Tallon, Luke
Morrison, W Ivan
Daubenberger, Claudia A
Nene, Vish
Knowles, Donald P
Bishop, Richard P
Silva, Joana C
Date
2020-10-29Journal
PLoS Neglected Tropical DiseasesPublisher
Public Library of ScienceType
Article
Metadata
Show full item recordAbstract
Theileria parva is an economically important, intracellular, tick-transmitted parasite of cattle. A live vaccine against the parasite is effective against challenge from cattle-transmissible T. parva but not against genotypes originating from the African Cape buffalo, a major wildlife reservoir, prompting the need to characterize genome-wide variation within and between cattle-and buffalo-associated T. parva populations. Here, we describe a capture-based tar-get enrichment approach that enables, for the first time, de novo assembly of nearly com-plete T. parva genomes derived from infected host cell lines. This approach has exceptionally high specificity and sensitivity and is successful for both cattle-and buffalo-derived T. parva parasites. De novo genome assemblies generated for cattle genotypes differ from the reference by ~54K single nucleotide polymorphisms (SNPs) throughout the 8.31 Mb genome, an average of 6.5 SNPs/kb. We report the first buffalo-derived T. parva genome, which is ~20 kb larger than the genome from the reference, cattle-derived, Muguga strain, and contains 25 new potential genes. The average non-synonymous nucleotide diversity (πN) per gene, between buffalo-derived T. parva and the Muguga strain, was 1.3%. This remarkably high level of genetic divergence is supported by an average Wright’s fixa-tion index (FST), genome-wide, of 0.44, reflecting a degree of genetic differentiation between cattle-and buffalo-derived T. parva parasites more commonly seen between, rather than within, species. These findings present clear implications for vaccine development, further demonstrated by the ability to assemble nearly all known antigens in the buffalo-derived strain, which will be critical in design of next generation vaccines. The DNA capture approach used provides a clear advantage in specificity over alternative T. parva DNA enrichment methods used previously, such as those that utilize schizont purification, is less labor intensive, and enables in-depth comparative genomics in this apicomplexan parasite. © 2020 Palmateer et al.Identifier to cite or link to this item
http://hdl.handle.net/10713/14066ae974a485f413a2113503eed53cd6c53
10.1371/journal.pntd.0008781
Scopus Count
Collections
Related articles
- Variant analysis of the sporozoite surface antigen gene reveals that asymptomatic cattle from wildlife-livestock interface areas in northern Tanzania harbour buffalo-derived T. parva.
- Authors: Mwamuye MM, Odongo D, Kazungu Y, Kindoro F, Gwakisa P, Bishop RP, Nijhof AM, Obara I
- Issue date: 2020 Nov
- Antigen gene and variable number tandem repeat (VNTR) diversity in Theileria parva parasites from Ankole cattle in south-western Uganda: Evidence for conservation in antigen gene sequences combined with extensive polymorphism at VNTR loci.
- Authors: Nanteza A, Obara I, Kasaija P, Mwega E, Kabi F, Salih DA, Njahira M, Njuguna J, Odongo D, Bishop RP, Skilton RA, Ahmed J, Clausen PH, Lubega GW
- Issue date: 2020 Mar
- Ancient diversity and geographical sub-structuring in African buffalo Theileria parva populations revealed through metagenetic analysis of antigen-encoding loci.
- Authors: Hemmink JD, Sitt T, Pelle R, de Klerk-Lorist LM, Shiels B, Toye PG, Morrison WI, Weir W
- Issue date: 2018 Mar
- Diversity of two Theileria parva CD8+ antigens in cattle and buffalo-derived parasites in Tanzania.
- Authors: Kerario II, Chenyambuga SW, Mwega ED, Rukambile E, Simulundu E, Simuunza MC
- Issue date: 2019 Aug
- Similar levels of diversity in the gene encoding the p67 sporozoite surface protein of Theileria parva are observed in blood samples from buffalo and cattle naturally infected from buffalo.
- Authors: Sitt T, Henson S, Morrison WI, Toye P
- Issue date: 2019 May