{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T10:31:32Z","timestamp":1779100292698,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013699","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000}}],"reference-count":84,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2022YFD1800200 and 2024YFD1800100"],"award-info":[{"award-number":["2022YFD1800200 and 2024YFD1800100"]}]},{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["\u211632573390"],"award-info":[{"award-number":["\u211632573390"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Science Fund for Creative Research Groups of Gansu Province, China","award":["24JRRA812"],"award-info":[{"award-number":["24JRRA812"]}]},{"name":"Science Fund for Creative Research Groups of Gansu Province, China","award":["22JR5RA024"],"award-info":[{"award-number":["22JR5RA024"]}]},{"name":"Agricultural Science and Technology Innovation Program, China","award":["CAAS-ASTIP-2016-LVRI"],"award-info":[{"award-number":["CAAS-ASTIP-2016-LVRI"]}]},{"name":"NBCIS","award":["CARS-37"],"award-info":[{"award-number":["CARS-37"]}]},{"name":"National Parasitic Resources Center, China","award":["NPRC-2019-194-30"],"award-info":[{"award-number":["NPRC-2019-194-30"]}]},{"name":"Leading Fund of Lanzhou Veterinary Research Institute, China","award":["LVRI-SZJJ-202105"],"award-info":[{"award-number":["LVRI-SZJJ-202105"]}]},{"name":"State Key Laboratory for Animal Disease Control and Prevention, China","award":["SKLVEB2021CGQD02 to GG and SKLADCP2023HP04"],"award-info":[{"award-number":["SKLVEB2021CGQD02 to GG and SKLADCP2023HP04"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Babesiosis is an emerging and re-emerging zoonosis that is prevalent worldwide, caused by over 100\n                    <jats:italic>Babesia<\/jats:italic>\n                    species. These intracellular parasites efficiently invade host red bloods cells, replicate rapidly, and exit the infected cells to cause clinical symptoms. However, the underlying mechanisms of regulating this asexual stage is largely unknown. Here, we generated a chromosome-level reference assembly of a novel\n                    <jats:italic>Babesia<\/jats:italic>\n                    species,\n                    <jats:italic>Babesia xinjiangensis<\/jats:italic>\n                    . Using single-copy orthologous genes, we confirmed its phylogenetic relationships with other apicomplexan parasites and estimated its speciation time. We identified species-specific gene families and core gene families that could be responsible for species speciation and immune evasion. Furthermore, we also used a single-cell RNA-sequencing (scRNA-seq) protocol to uncover hidden transcriptional variations in the asexual stages of this unicellular\n                    <jats:italic>Babesia<\/jats:italic>\n                    parasite and its cell-to-cell heterogeneity. We inferred the replication cycle and performed a pseudotime analysis to speculate the gene expression profiles. Although the peak expression times of most epigenetic markers and transcription factors were confined to specific phases, BxAP2-M2 (GWHPERCV002055) is constantly expressed during asexual development progression. Genetic analyses revealed that BxAP2-M2 directly or indirectly regulates the expression of rhoptry proteins and membrane proteins, which may play critical roles in the parasite\u2019s invasion of red blood cells and the merozoite morphology. Our findings provide valuable markers of asexual replication, including some that are specific to\n                    <jats:italic>Babesia<\/jats:italic>\n                    gametocytes, and regulators specific to distinct cell-cycle phases.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013699","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T18:54:40Z","timestamp":1763060080000},"page":"e1013699","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparative genomics, integrated with single-cell sequencing and genetic analyses, reveal roles of transcription factor AP2-M2 in asexual replication of Babesia parasite"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2076-3764","authenticated-orcid":true,"given":"Jinming","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yijun","family":"Chai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxin","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jifei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinxin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guiquan","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"issue":"3","key":"ppat.1013699.ref001","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1128\/CMR.13.3.451","article-title":"Babesiosis","volume":"13","author":"MJ Homer","year":"2000","journal-title":"Clin Microbiol Rev"},{"issue":"4","key":"ppat.1013699.ref002","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s11250-006-4181-2","article-title":"Estimated direct economic costs associated with tick-borne diseases on cattle in Tanzania","volume":"38","author":"FM Kivaria","year":"2006","journal-title":"Trop Anim Health Prod"},{"key":"ppat.1013699.ref003","article-title":"Babesiosis of cattle","author":"R Bock","year":"2004","journal-title":"Parasitology"},{"issue":"1","key":"ppat.1013699.ref004","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1186\/s13071-021-04948-3","article-title":"Babesiosis as a potential threat for bovine production in China","volume":"14","author":"L He","year":"2021","journal-title":"Parasit Vectors"},{"issue":"2","key":"ppat.1013699.ref005","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3390\/healthcare6020049","article-title":"Human Babesiosis Caused by Babesia duncani Has Widespread Distribution across Canada","volume":"6","author":"JD Scott","year":"2018","journal-title":"Healthcare (Basel)"},{"issue":"1","key":"ppat.1013699.ref006","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/s12915-022-01361-9","article-title":"Comparative genomic analysis of Babesia duncani responsible for human babesiosis","volume":"20","author":"J Wang","year":"2022","journal-title":"BMC Biol"},{"issue":"2","key":"ppat.1013699.ref007","article-title":"Detection of US and Kobe\u2010type Babesia microti in ticks collected from small mammals of the Republic of Korea","volume":"54","author":"TY Kim","year":"2024","journal-title":"Entomological Research"},{"issue":"7","key":"ppat.1013699.ref008","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1093\/cid\/ciy212","article-title":"Human Babesiosis Caused by a Babesia crassa-Like Pathogen: A Case Series","volume":"67","author":"N Jia","year":"2018","journal-title":"Clin Infect 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Wang","year":"2023","journal-title":"Int J Parasitol"},{"issue":"1","key":"ppat.1013699.ref012","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1186\/s13071-020-04250-8","article-title":"Insights into the phylogenetic relationships and drug targets of Babesia isolates infective to small ruminants from the mitochondrial genomes","volume":"13","author":"X Wang","year":"2020","journal-title":"Parasit Vectors"},{"key":"ppat.1013699.ref013","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.vetpar.2018.02.013","article-title":"Haemoparasitic agents associated with ovine babesiosis: A possible negative interaction between Babesia ovis and Theileria ovis","volume":"252","author":"F Sevinc","year":"2018","journal-title":"Vet Parasitol"},{"issue":"5","key":"ppat.1013699.ref014","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.pt.2019.01.007","article-title":"Babesia Life Cycle - When Phylogeny Meets Biology","volume":"35","author":"M 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