Univ Fed Para, Lab Tecnol Biomol Bioinformat, Inst Ciencias Biol, Belem, Para - Brazil
 Inst Carlos Chagas, Fundacao Oswaldo Cruz, Curitiba, Parana - Brazil
 Inst Butantan, Lab Especial Toxinol Aplicada, Sao Paulo - Brazil
Total Affiliations: 6
JUN 22 2020.
Web of Science Citations:
BackgroundDNA replication in trypanosomatids operates in a uniquely challenging environment, since most of their genomes are constitutively transcribed. Trypanosoma cruzi, the etiological agent of Chagas disease, presents high variability in both chromosomes size and copy number among strains, though the underlying mechanisms are unknown.ResultsHere we have mapped sites of DNA replication initiation across the T. cruzi genome using Marker Frequency Analysis, which has previously only been deployed in two related trypanosomatids. The putative origins identified in T. cruzi show a notable enrichment of GC content, a preferential position at subtelomeric regions, coinciding with genes transcribed towards the telomeres, and a pronounced enrichment within coding DNA sequences, most notably in genes from the Dispersed Gene Family 1 (DGF-1).ConclusionsThese findings suggest a scenario where collisions between DNA replication and transcription are frequent, leading to increased genetic variability, as seen by the increase SNP levels at chromosome subtelomeres and in DGF-1 genes containing putative origins. (AU)