Insights into the evolution, virulence and speciation of Babesia MO1 and Babesia divergens through multiomics analyses

All datasets generated for the current study are accessible in the NCBI/SRA repository under Bioproject PRJNA1032622 (reviewer link). Specifically, the datasets include PacBio HiFi reads (SRA accession number SRR26661633), B. MO1 genome, RNA-Seq (SRA accession number SRR26661632), Hi-C reads (SRA accession number SRR26661630, SRR26661631), ChIP-Seq reads (SRA accession number SRR26661627, SRR26661629, SRR26661626, SRR26661628, SRR26661625).The Babesia MO1 genome was processed using the gene annotation pipeline FunAnnotate v1.8.9 (https://github.com/nextgenusfs/funannotate) and PAP (https://github.com/kjestradag/PAP) pipelines. FunAnnotate was supplied with the MO1 IsoSeq isoforms computed above, along with protein sets of B. bigemina, B. bovis, B. microti, P. falciparum, Toxoplasma gondii, T. orientalis, T. parva and all UniProt/SwissProt protein models. Functional annotations were obtained using InterProScan v5.55-88 with default parameters. For B. divergens Rouen 87, gene annotations were transferred to the improved assembly presented here using the PATT pipeline (https://github.com/kjestradag/PATT). Gene models form B. MO1 were constructed based on annotations of evolutionarily-related species and further refined using PacBio Iso-seq data specific to B. MO1.Babesia MO1, B. divergens Rouen 87 and a B. divergens clinical isolate from Spain were cultured using human A+ blood obtained from healthy volunteer donors [Citation6]. The blood was sourced from the American red cross (US), the Interstate Blood Bank (US), or the Blood Transfusion Center (Spain), adhering to approved protocols and in compliance with the relevant institutional guidelines and regulations.

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Английский. Babesiosis, caused by protozoan parasites of the genus Babesia, is an emerging tick-borne disease of significance for both human and animal health. Babesia parasites infect erythrocytes of vertebrate hosts where they develop and multiply rapidly to cause the pathological symptoms associated with the disease. The identification of new Babesia species underscores the ongoing risk of zoonotic pathogens capable of infecting humans, a concern amplified by anthropogenic activities and environmental changes. One such pathogen, Babesia MO1, previously implicated in severe cases of human babesiosis in the United States, was initially considered a subspecies of B. divergens, the predominant agent of human babesiosis in Europe. Here we report comparative multiomics analyses of B. divergens and B. MO1 that offer insight into their biology and evolution. Our analysis shows that despite their highly similar genomic sequences, substantial genetic and genomic divergence occurred throughout their evolution resulting in major differences in gene functions, expression and regulation, replication rates and susceptibility to antiparasitic drugs. Furthermore, both pathogens have evolved distinct classes of multigene families, crucial for their pathogenicity and adaptation to specific mammalian hosts. Leveraging genomic information for B. MO1, B. divergens, and other members of the Babesiidae family within Apicomplexa provides valuable insights into the evolution, diversity, and virulence of these parasites. This knowledge serves as a critical tool in preemptively addressing the emergence and rapid transmission of more virulent strains.