Replication origin location might contribute to genetic variability in Trypanosoma cruzi

• Published in: BMC genomics 2020-06, Vol.21 (1), p.414-414, Article 414
• Main Authors: de Araujo, Christiane Bezerra, da Cunha, Julia Pinheiro Chagas, Inada, Davi Toshio, Damasceno, Jeziel, Lima, Alex Ranieri Jerônimo, Hiraiwa, Priscila, Marques, Catarina, Gonçalves, Evonnildo, Nishiyama-Junior, Milton Yutaka, McCulloch, Richard, Elias, Maria Carolina
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Base Composition; Cell cycle; Cell division; Chagas disease; Chromosomes; Copy number; Deoxyribonucleic acid; DGF-1; DNA; DNA biosynthesis; DNA Replication; DNA sequencing; DNA, Protozoan - genetics; Etiology; Flexibility; Frequency analysis; Gene sequencing; Genes; Genetic variability; Genomes; Genomics; High-Throughput Nucleotide Sequencing; Nucleotide sequence; Origins; Polymorphism, Single Nucleotide; Proteins; Protozoa; Replication; Replication initiation; Replication Origin; Replication origins; Single-nucleotide polymorphism; Telomeres; Transcription; Transcription (Genetics); Triatoma - parasitology; Trypanosoma cruzi; Trypanosoma cruzi - genetics; Trypanosoma cruzi - isolation & purification; Vector-borne diseases; Whole Genome Sequencing - methods
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-020-06803-8

DNA 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. Here 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). These 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.