Integrating high-throughput analysis to create an atlas of replication origins in Trypanosoma cruzi in the context of genome structure and variability

Author(s)

Vitarelli, Marcela de Oliveira ; Franco, Thiago Andrade ; Pires, David da Silva ; Lima, Alex Ranieri Jeronimo ; Viala, Vincent Louis ; Kraus, Amelie Johanna ; de Azevedo, Inacio de Loiola Meirelles Junqueira ; da Cunha, Julia Pinheiro Chagas ; Elias, Maria Carolina

• Document type: Journal article
• Source: MBIO; v. 15, n. 4, p. 25-pg., 2024-03-05.

Abstract

Trypanosoma cruzi is the etiologic agent of the most prevalent human parasitic disease in Latin America, Chagas disease. Its genome is rich in multigenic families that code for virulent antigens and are present in the rapidly evolving genomic compartment named Disruptive. DNA replication is a meticulous biological process in which flaws can generate mutations and changes in chromosomal and gene copy numbers. Here, integrating high-throughput and single-molecule analyses, we were able to identify Predominant, Flexible, and Dormant Orc1Cdc6-dependent origins as well as Orc1Cdc6-independent origins. Orc1Cdc6-dependent origins were found in multigenic family loci, while independent origins were found in the Core compartment that contains conserved and hypothetical protein-coding genes, in addition to multigenic families. In addition, we found that Orc1Cdc6 density is related to the firing of origins and that Orc1Cdc6-binding sites within fired origins are depleted of a specific class of nucleosomes that we previously categorized as dynamic. Together, these data suggest that Orc1Cdc6-dependent origins may contribute to the rapid evolution of the Disruptive compartment and, therefore, to the success of T. cruzi infection and that the local epigenome landscape is also involved in this process. (AU)

• FAPESP's process: 16/50050-2 - How do common and diverged features of the replicative stress response shape the biology of TriTryp parasites?
• Grantee: Maria Carolina Quartim Barbosa Elias Sabbaga
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/04483-2 - Functional dynamics of Orc1b protein: a ChIP-seq analysis
• Grantee: Marcela de Oliveira Vitarelli
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 20/00694-6 - How DNA replication contributes for the success of infection caused by Trypanosoma cruzi
• Grantee: Maria Carolina Quartim Barbosa Elias Sabbaga
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/07693-2 - Functional dynamics of Orc1b protein during the life cycle of Trypanosoma
• Grantee: Marcela de Oliveira Vitarelli
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 22/01900-4 - Dynamics of DNA replication in Trypanosoma cruzi: consequences of replicative stress
• Grantee: Thiago Andrade Franco
• Support Opportunities: Scholarships in Brazil - Post-Doctoral