The Dynamics of Replication in <i>Trypanosoma cruzi</i> Parasites by Single‐Molecule Analysis

Araujo, Christiane B. de; Calderano, Simone Guedes; Elias, Maria Carolina

doi:10.1111/jeu.12676

Cited by 4 publications

(3 citation statements)

References 30 publications

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“…Therefore, we wondered if the putative ORIs detected would be enough to allow T. cruzi to fully replicate its chromosomes during S phase. Previous analysis by DNA combing (which can detect any replication initiation event, including constitutive, flexible and dormant origins, but without reference to genome location) in T. cruzi CL Brener suggested a median inter-origin distance of 171.1 kb [41], which can be extrapolated to a total of 85 origins, which is close to 103 and 110 putative consensus origins mapped in the P and S haplotypes in this analysis. Therefore, it indicates that MFA-seq analysis was able to cover origins used by T. cruzi to replicate entire genome at least in an unstressed condition.…”

Section: Discussionsupporting

confidence: 52%

Replication origin location might contribute to genetic variability in Trypanosoma cruzi

et al. 2020

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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.

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Section: Discussionsupporting

confidence: 52%

Replication origin location might contribute to genetic variability in Trypanosoma cruzi

et al. 2020

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“…Interestingly, the majority of the putative predicted ORIs presented a great abundance within coding DNA sequences and showed a great G + C content enrichment (65% of average), while the genomic regions had a maximum of 54%. Also, another analysis with the same strain of T. cruzi by DNA combing, which can detect any replication initiation event (including constitutive, flexible and dormant origins, but without reference to genome location), displayed a median inter-origin distance of 1711 kb [ 87 ].…”

Section: Genetic Diversity and Genome Structure Of T Crmentioning

confidence: 99%

Trypanosoma Cruzi Genome: Organization, Multi-Gene Families, Transcription, and Biological Implications

Herreros-Cabello

Callejas-Hernández

Gironès

et al. 2020

Genes

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Chagas disease caused by the parasite Trypanosoma cruzi affects millions of people. Although its first genome dates from 2005, its complexity hindered a complete assembly and annotation. However, the new sequencing methods have improved genome annotation of some strains elucidating the broad genetic diversity and complexity of this parasite. Here, we reviewed the genomic structure and regulation, the genetic diversity, and the analysis of the principal multi-gene families of the recent genomes for several strains. The telomeric and sub-telomeric regions are sites with high recombination events, the genome displays two different compartments, the core and the disruptive, and the genome plasticity seems to play a key role in the survival and the infection process. Trypanosoma cruzi (T. cruzi) genome is composed mainly of multi-gene families as the trans-sialidases, mucins, and mucin-associated surface proteins. Trans-sialidases are the most abundant genes in the genome and show an important role in the effectiveness of the infection and the parasite survival. Mucins and MASPs are also important glycosylated proteins of the surface of the parasite that play a major biological role in both insect and mammal-dwelling stages. Altogether, these studies confirm the complexity of T. cruzi genome revealing relevant concepts to better understand Chagas disease.

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“…For each organism analyzed, we used as parameters for the formula up-to-date data available in the TriTrypDB database (www.tritrypdb.org), NCBI database (www.ncbi.nlm.nih.gov), and data reported in the studies related [3,8,[11][12][13][23][24][25][26] (see Table 1 for more details).…”

Section: Estimation Of the Minimum Number Of Replication Origins (Mo)mentioning

confidence: 99%

Comparative Analysis of the Minimum Number of Replication Origins in Trypanosomatids and Yeasts

Silva

Vitarelli

Souza

et al. 2020

Genes

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Single-celled eukaryote genomes predominantly replicate through multiple origins. Although origin usage during the S-phase has been elucidated in some of these organisms, few studies have comparatively approached this dynamic. Here, we developed a user-friendly website able to calculate the length of the cell cycle phases for any organism. Next, using a formula developed by our group, we showed a comparative analysis among the minimum number of replication origins (MO) required to duplicate an entire chromosome within the S-phase duration in trypanosomatids (Trypanosoma cruzi, Leishmania major, and Trypanosoma brucei) and yeasts (Saccharomyces cerevisiae and Schizosaccharomyces pombe). Using the data obtained by our analysis, it was possible to predict the MO required in a situation of replication stress. Also, our findings allow establishing a threshold for the number of origins, which serves as a parameter for genome approaches that map origins. Moreover, our data suggest that when compared to yeasts, trypanosomatids use much more origins than the minimum needed. This is the first time a comparative analysis of the minimum number of origins has been successfully applied. These data may provide new insight into the understanding of the replication mechanism and a new methodological framework for studying single-celled eukaryote genomes.

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The Dynamics of Replication in Trypanosoma cruzi Parasites by Single‐Molecule Analysis

Cited by 4 publications

References 30 publications

Replication origin location might contribute to genetic variability in Trypanosoma cruzi

Replication origin location might contribute to genetic variability in Trypanosoma cruzi

Trypanosoma Cruzi Genome: Organization, Multi-Gene Families, Transcription, and Biological Implications

Comparative Analysis of the Minimum Number of Replication Origins in Trypanosomatids and Yeasts

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