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Genetic exchange can occur among natural <jats:italic>Leishmania<\/jats:italic> populations and hybrids can now be produced experimentally, with limitations. Feeding <jats:italic>Phlebotomus orientalis<\/jats:italic> or <jats:italic>Phlebotomus argentipes<\/jats:italic> on two strains of <jats:italic>Leishmania donovani<\/jats:italic> yielded hybrid progeny, selected using double drug resistance and fluorescence markers. Fluorescence activated cell sorting of cultured clones derived from these hybrids indicated diploid progeny. Multilocus sequence typing of the clones showed hybridisation and nuclear heterozygosity, although with inheritance of single haplotypes in a kinetoplastid target. Comparative genomics showed diversity of clonal progeny between single chromosomes, and extraordinary heterozygosity across all 36 chromosomes. Diversity between progeny was seen for the HASPB antigen, which has been noted previously as having implications for design of a therapeutic vaccine. Genomic diversity seen among <jats:italic>Leishmania<\/jats:italic> strains and hybrid progeny is of great importance in understanding the epidemiology and control of leishmaniasis. As an outcome of this study we strongly recommend that wider biological archives of different <jats:italic>Leishmania<\/jats:italic> species from endemic regions should be established and made available for comparative genomics. However, in parallel, performance of genetic crosses and genomic comparisons should give fundamental insight into the specificity, diversity and limitations of candidate diagnostics, vaccines and drugs, for targeted control of leishmaniasis.<\/jats:p>","DOI":"10.1371\/journal.pntd.0011920","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T18:25:03Z","timestamp":1706725503000},"page":"e0011920","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Comparative genomics of Leishmania donovani progeny from genetic crosses in two sand fly species and impact on the diversity of diagnostic and vaccine candidates"],"prefix":"10.1371","volume":"18","author":[{"given":"Jovana","family":"S\u00e1dlov\u00e1","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Yeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Mateus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jody","family":"Phelan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le Anh","family":"Hai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3385-2536","authenticated-orcid":true,"given":"Tapan","family":"Bhattacharyya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kurtev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ondrej","family":"Sebesta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitka","family":"Myskova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Seblova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Andersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Florez de Sessions","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Volf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Miles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"pntd.0011920.ref001","unstructured":"World Health Organization, Leishmaniasis, Geneva, Switzerland, 2023, January."},{"key":"pntd.0011920.ref002","first-page":"1","volume-title":"Control of the leishmaniases Technical Report Series 949","author":"World Health Organization","year":"2010"},{"key":"pntd.0011920.ref003","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1017\/S0031182016002092","article-title":"An appraisal of the taxonomy and nomenclature of trypanosomatids presently classified as Leishmania and Endotrypanum","volume":"145","author":"OA Espinosa","year":"2018","journal-title":"Parasitology"},{"key":"pntd.0011920.ref004","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1186\/1756-3305-5-276","article-title":"Leishmania development in sand flies: parasite-vector interactions overview","volume":"5","author":"A Dost\u00e1lov\u00e1","year":"2012","journal-title":"Parasit Vectors"},{"key":"pntd.0011920.ref005","doi-asserted-by":"crossref","first-page":"9375","DOI":"10.1073\/pnas.0703678104","article-title":"Evolutionary and geographical history of the Leishmania donovani complex with a revision of current taxonomy","volume":"104","author":"J Lukes","year":"2007","journal-title":"Proc. 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