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Abstract
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.
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1 Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA
2 Unidad Universitaria de Secuenciacion Masiva y Bioinformatica, Instituto de Biotecnologia, Universidad Nacional Autonoma de Mexico, Cuernavaca, Morelos, Mexico
3 Laboratorio de Referencia e Investigación en Parasitología, National Center for Microbiology, Instituto de Salud Carlos III, Majadahonda, Spain
4 Department of Computer Science and Engineering, University of California, Riverside, CA, USA
5 LIRMM – Université de Montpellier, CNRS, Montpellier, France
6 AGAP Institut, Université de Montpellier, CIRAD, INRAE, Institut Agro, Montpellier, France
7 MIVEGEC, Univ. Montpellier, CNRS, IRD, CHU, Montpellier, France
8 Unité Molécules de Communication et Adaptation des Microorganismes (MCAM, UMR7245), Muséum National d’Histoire Naturelle, CNRS, Paris, France
9 Laboratorio de Referencia e Investigación en Infecciones Bacterianas Transmitidas por Agua y Alimentos, National Center for Microbiology, Instituto de Salud Carlos III, Majadahonda, Spain
10 Institut de Biologie Computationnelle (IBC), and Institut de Recherche en Cancérologie de Montpellier (IRCM - INSERM U1194), Institut régional du Cancer Montpellier (ICM) & Université de Montpellier, Montpellier, France
11 Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, USA
12 Department of Biology, University of Pennsylvania, Philadelphia, PA, USA




