Dataset Information

Replication origin location might contribute to genetic variability in Trypanosoma cruzi.

ABSTRACT: BACKGROUND: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. RESULTS: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). CONCLUSIONS: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.

SUBMITTER: de Araujo CB

PROVIDER: S-EPMC7310030 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Replication origin location might contribute to genetic variability in Trypanosoma cruzi.

de Araujo Christiane Bezerra CB da Cunha Julia Pinheiro Chagas JPC Inada Davi Toshio DT Damasceno Jeziel J Lima Alex Ranieri Jerônimo ARJ Hiraiwa Priscila P Marques Catarina C Gonçalves Evonnildo E Nishiyama-Junior Milton Yutaka MY McCulloch Richard R Elias Maria Carolina MC

BMC genomics 20200622 1

<h4>Background</h4>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.<h4>Results</h4>Here we have mapped sites of DNA replication initiation across the T. cruzi genome using Marker Frequency Analysis, which has previousl ...[more]

PMID: 32571205

Similar Datasets

Project description:BACKGROUND: Trypanosoma cruzi, the causal agent of Chagas Disease, affects more than 16 million people in Latin America. The clinical outcome of the disease results from a complex interplay between environmental factors and the genetic background of both the human host and the parasite. However, knowledge of the genetic diversity of the parasite, is currently limited to a number of highly studied loci. The availability of a number of genomes from different evolutionary lineages of T. cruzi provides an unprecedented opportunity to look at the genetic diversity of the parasite at a genomic scale. RESULTS: Using a bioinformatic strategy, we have clustered T. cruzi sequence data available in the public domain and obtained multiple sequence alignments in which one or two alleles from the reference CL-Brener were included. These data covers 4 major evolutionary lineages (DTUs): TcI, TcII, TcIII, and the hybrid TcVI. Using these set of alignments we have identified 288,957 high quality single nucleotide polymorphisms and 1,480 indels. In a reduced re-sequencing study we were able to validate ~ 97% of high-quality SNPs identified in 47 loci. Analysis of how these changes affect encoded protein products showed a 0.77 ratio of synonymous to non-synonymous changes in the T. cruzi genome. We observed 113 changes that introduce or remove a stop codon, some causing significant functional changes, and a number of tri-allelic and tetra-allelic SNPs that could be exploited in strain typing assays. Based on an analysis of the observed nucleotide diversity we show that the T. cruzi genome contains a core set of genes that are under apparent purifying selection. Interestingly, orthologs of known druggable targets show statistically significant lower nucleotide diversity values. CONCLUSIONS: This study provides the first look at the genetic diversity of T. cruzi at a genomic scale. The analysis covers an estimated ~ 60% of the genetic diversity present in the population, providing an essential resource for future studies on the development of new drugs and diagnostics, for Chagas Disease. These data is available through the TcSNP database (http://snps.tcruzi.org).

Dataset Information

Replication origin location might contribute to genetic variability in Trypanosoma cruzi.

Publications

Replication origin location might contribute to genetic variability in Trypanosoma cruzi.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets