Details

Autor(en) / Beteiligte

• Vitarelli, Marcela de Oliveira
• Franco, Thiago Andrade
• Pires, David da Silva
• Lima, Alex Ranieri Jerônimo
• Viala, Vincent Louis
• Kraus, Amelie Johanna
• de Azevedo, Inácio de Loiola Meirelles Junqueira
• da Cunha, Julia Pinheiro Chagas
• Elias, Maria Carolina
• Soldati-Favre, Dominique

Titel

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

Ist Teil von

• mBio, 2024-04, Vol.15 (4), p.e0031924-e0031924

Ort / Verlag

United States: American Society for Microbiology

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 infection and that the local epigenome landscape is also involved in this process.IMPORTANCE , responsible for Chagas disease, affects millions globally, particularly in Latin America. Lack of vaccine or treatment underscores the need for research. Parasite's genome, with virulent antigen-coding multigenic families, resides in the rapidly evolving Disruptive compartment. Study sheds light on the parasite's dynamic DNA replication, discussing the evolution of the Disruptive compartment. Therefore, the findings represent a significant stride in comprehending 's biology and the molecular bases that contribute to the success of infection caused by this parasite.