scholarly journals Cell Biology of the Trypanosome Genome

2010 ◽  
Vol 74 (4) ◽  
pp. 552-569 ◽  
Author(s):  
Jan-Peter Daniels ◽  
Keith Gull ◽  
Bill Wickstead

SUMMARY Trypanosomes are a group of protozoan eukaryotes, many of which are major parasites of humans and livestock. The genomes of trypanosomes and their modes of gene expression differ in several important aspects from those of other eukaryotic model organisms. Protein-coding genes are organized in large directional gene clusters on a genome-wide scale, and their polycistronic transcription is not generally regulated at initiation. Transcripts from these polycistrons are processed by global trans-splicing of pre-mRNA. Furthermore, in African trypanosomes, some protein-coding genes are transcribed by a multifunctional RNA polymerase I from a specialized extranucleolar compartment. The primary DNA sequence of the trypanosome genomes and their cellular organization have usually been treated as separate entities. However, it is becoming increasingly clear that in order to understand how a genome functions in a living cell, we will need to unravel how the one-dimensional genomic sequence and its trans-acting factors are arranged in the three-dimensional space of the eukaryotic nucleus. Understanding this cell biology of the genome will be crucial if we are to elucidate the genetic control mechanisms of parasitism. Here, we integrate the concepts of nuclear architecture, deduced largely from studies of yeast and mammalian nuclei, with recent developments in our knowledge of the trypanosome genome, gene expression, and nuclear organization. We also compare this nuclear organization to those in other systems in order to shed light on the evolution of nuclear architecture in eukaryotes.

2022 ◽  
Vol 8 (1) ◽  
pp. 7
Author(s):  
Hyung Chul Kim ◽  
Emmitt R. Jolly

Trypanosoma brucei is a parasitic protist that causes African sleeping sickness. The establishment of T. brucei cell lines has provided a significant advantage for the majority of T. brucei research. However, these cell lines were isolated and maintained in culture for decades, occasionally accumulating changes in gene expression. Since trypanosome strains have been maintained in culture for decades, it is possible that difference may have accumulated in fast-evolving non-coding RNAs between trypanosomes from the wild and those maintained extensively in cultures. To address this, we compared the lncRNA expression profile of trypanosomes maintained as cultured cell lines (CL) to those extracted from human patients, wildtype (WT). We identified lncRNAs from CL and WT from available transcriptomic data and demonstrate that CL and WT have unique sets of lncRNAs expressed. We further demonstrate that the unique and shared lncRNAs are differentially expressed between CL and WT parasites, and that these lncRNAs are more evenly up-regulated and down-regulated than protein-coding genes. We validated the expression of these lncRNAs using qPCR. Taken together, this study demonstrates that lncRNAs are differentially expressed between cell lines and wildtype T. brucei and provides evidence for potential evolution of lncRNAs, specifically in T. brucei maintained in culture.


2021 ◽  
Author(s):  
Alex RJ Lima ◽  
Saloe B Poubel ◽  
Juliana N Roson ◽  
Loyze PO de Lima ◽  
Hellida M Costa-Silva ◽  
...  

Background: Genomic organization and gene expression regulation in trypanosomes are remarkable because protein-coding genes are organized into codirectional gene clusters with unrelated functions. Moreover, there is no dedicated promoter for each gene, resulting in polycistronic gene transcription, with posttranscriptional control playing a major role. Nonetheless, these parasites harbor epigenetic modifications at critical regulatory genome features that dynamically change among parasite stages, which are not fully understood. Results: Here, we investigated the impact of chromatin changes in a scenario commanded by posttranscriptional control exploring the parasite Trypanosoma cruzi and its differentiation program using genome-wide approaches supported by transmission electron microscopy. The integration of FAIRE and MNase-seq data, two complementary epigenomic approaches, enabled us to identify differences in T. cruzi genome compartments, putative transcriptional start regions and virulence factors. In addition, we also detected developmental chromatin regulation at tRNA loci (tDNA), which seems to be linked to the translation regulatory mechanism required for parasite differentiation. Strikingly, a positive correlation was observed between active chromatin and steady-state transcription levels. Conclusion: Taken together, our results indicate that chromatin changes reflect the unusual gene expression regulation of trypanosomes and the differences among parasite developmental stages, even in the context of a lack of canonical transcriptional control of protein-coding genes.


2021 ◽  
Author(s):  
Alex RJ Lima ◽  
Saloe B Poubel ◽  
Juliana N Rosón ◽  
Loyze PO de Lima ◽  
Hellida M Costa-Silva ◽  
...  

Abstract Background: Genomic organization and gene expression regulation in trypanosomes are remarkable because protein-coding genes are organized into codirectional gene clusters with unrelated functions. Moreover, there is no dedicated promoter for each gene, resulting in polycistronic gene transcription, with posttranscriptional control playing a major role. Nonetheless, these parasites harbor epigenetic modifications at critical regulatory genome features that dynamically change among parasite stages, which are not fully understood. Results: Here, we investigated the impact of chromatin changes in a scenario commanded by posttranscriptional control exploring the parasite Trypanosoma cruzi and its differentiation program using genome-wide approaches supported by transmission electron microscopy. The integration of FAIRE and MNase-seq data, two complementary epigenomic approaches, enabled us to identify differences in T. cruzi genome compartments, putative transcriptional start regions and virulence factors. In addition, we also detected developmental chromatin regulation at tRNA loci (tDNA), which seems to be linked to the translation regulatory mechanism required for parasite differentiation. Strikingly, a positive correlation was observed between active chromatin and steady-state transcription levels. Conclusion: Taken together, our results indicate that chromatin changes reflect the unusual gene expression regulation of trypanosomes and the differences among parasite developmental stages, even in the context of a lack of canonical transcriptional control of protein-coding genes.


2018 ◽  
Vol 2 (1) ◽  
pp. 32
Author(s):  
Semir Dorić ◽  
Dinko Osmanković ◽  
Lada Lukić Bilela

Codon usage is considered as a modulator of gene expression, due to high correlation between codon usage, tRNA abundance and the level of gene expression. Adaptability is primarily manifested at gene level therefore mtDNA gene expression analysis may indicate trends toward the development of adaptive traits for specific environmental conditions. Moreover, modified gene expression patterns may result from such adaptations. Due to their sensitivity to environmental disturbances, great functional importance and accessibility ants (Family: Formicidae Latreille, 1802) are excellent model organisms for  molecular and bioinformatics genome analysis. This in silico simulation is based on the comparison of codon usage bias and the level of gene expression of currently available mitochondrial protein-coding genes of ant species that were sampled at quarry Ribnica (Kakanj, Bosnia and Herzegovina). MILC and MELP algorithms were used forcodon usage bias analysis and mitochondrial gene expression prediction, respectively. The analysis included four mtDNA protein-coding genes from eight selected species of ants totaling in 32 protein sequences. The results of codon usage analysis indicated no statistically significant differences in codon usage bias, as well as relative frequencies of the gene expression level.  The next step should be directed to molecular ecology studies, even using whole genome measures of gene expression (RNA-seq; transcriptomics) to capture molecular response to environmental challenges.


2020 ◽  
Vol 21 (11) ◽  
pp. 1068-1077
Author(s):  
Xiaochao Sun ◽  
Bin Yang ◽  
Qunye Zhang

: Many studies have shown that the spatial distribution of genes within a single chromosome exhibits distinct patterns. However, little is known about the characteristics of inter-chromosomal distribution of genes (including protein-coding genes, processed transcripts and pseudogenes) in different genomes. In this study, we explored these issues using the available genomic data of both human and model organisms. Moreover, we also analyzed the distribution pattern of protein-coding genes that have been associated with 14 common diseases and the insert/deletion mutations and single nucleotide polymorphisms detected by whole genome sequencing in an acute promyelocyte leukemia patient. We obtained the following novel findings. Firstly, inter-chromosomal distribution of genes displays a nonstochastic pattern and the gene densities in different chromosomes are heterogeneous. This kind of heterogeneity is observed in genomes of both lower and higher species. Secondly, protein-coding genes involved in certain biological processes tend to be enriched in one or a few chromosomes. Our findings have added new insights into our understanding of the spatial distribution of genome and disease- related genes across chromosomes. These results could be useful in improving the efficiency of disease-associated gene screening studies by targeting specific chromosomes.


2021 ◽  
Vol 6 ◽  
pp. 258
Author(s):  
Konrad Lohse ◽  
Alexander Mackintosh ◽  
Roger Vila ◽  
◽  
◽  
...  

We present a genome assembly from an individual male Aglais io (also known as Inachis io and Nymphalis io) (the European peacock; Arthropoda; Insecta; Lepidoptera; Nymphalidae). The genome sequence is 384 megabases in span. The majority (99.91%) of the assembly is scaffolded into 31 chromosomal pseudomolecules, with the Z sex chromosome assembled. Gene annotation of this assembly on Ensembl has identified 11,420 protein coding genes.


2015 ◽  
Vol 1 ◽  
pp. e33 ◽  
Author(s):  
Elisha D. Roberson

CRISPR/Cas9 is emerging as one of the most-used methods of genome modification in organisms ranging from bacteria to human cells. However, the efficiency of editing varies tremendously site-to-site. A recent report identified a novel motif, called the 3′GG motif, which substantially increases the efficiency of editing at all sites tested inC. elegans. Furthermore, they highlighted that previously published gRNAs with high editing efficiency also had this motif. I designed a Python command-line tool, ngg2, to identify 3′GG gRNA sites from indexed FASTA files. As a proof-of-concept, I screened for these motifs in six model genomes:Saccharomyces cerevisiae,Caenorhabditis elegans,Drosophila melanogaster,Danio rerio,Mus musculus, andHomo sapiens. I also scanned the genomes of pig (Sus scrofa) and African elephant (Loxodonta africana) to demonstrate the utility in non-model organisms. I identified more than 60 million single match 3′GG motifs in these genomes. Greater than 61% of all protein coding genes in the reference genomes had at least one unique 3′GG gRNA site overlapping an exon. In particular, more than 96% of mouse and 93% of human protein coding genes have at least one unique, overlapping 3′GG gRNA. These identified sites can be used as a starting point in gRNA selection, and the ngg2 tool provides an important ability to identify 3′GG editing sites in any species with an available genome sequence.


2017 ◽  
Author(s):  
Cristina Cruz ◽  
Monica Della Rosa ◽  
Christel Krueger ◽  
Qian Gao ◽  
Lucy Field ◽  
...  

AbstractTranscription of protein coding genes is accompanied by recruitment of COMPASS to promoter-proximal chromatin, which deposits di- and tri-methylation on histone H3 lysine 4 (H3K4) to form H3K4me2 and H3K4me3. Here we determine the importance of COMPASS in maintaining gene expression across lifespan in budding yeast. We find that COMPASS mutations dramatically reduce replicative lifespan and cause widespread gene expression defects. Known repressive functions of H3K4me2 are progressively lost with age, while hundreds of genes become dependent on H3K4me3 for full expression. Induction of these H3K4me3 dependent genes is also impacted in young cells lacking COMPASS components including the H3K4me3-specific factor Spp1. Remarkably, the genome-wide occurrence of H3K4me3 is progressively reduced with age despite widespread transcriptional induction, minimising the normal positive correlation between promoter H3K4me3 and gene expression. Our results provide clear evidence that H3K4me3 is required to attain normal expression levels of many genes across organismal lifespan.


2019 ◽  
Author(s):  
Change Laura Tan

AbstractPublic access to thousands of completely sequenced and annotated genomes provides a great opportunity to address the relationships of different organisms, at the molecular level and on a genome-wide scale. Via comparing the phylogenetic profiles of all protein-coding genes in 317 model species described in the OrthoInspector3.0 database, we found that approximately 29.8% of the total protein-coding genes were orphan genes (genes unique to a specific species) while < 0.01% were universal genes (genes with homologs in each of the 317 species analyzed). When weighted by potential birth event, the orphan genes comprised 82% of the total, while the universal genes accounted for less than 0.00008%. Strikingly, as the analyzed genomes increased, the sum total of universal and nearly-universal genes plateaued while that of orphan and nearly-orphan genes grew continuously. When the compared species increased to the inclusion of 3863 bacteria, 711 eukaryotes, and 179 archaea, not one of the universal genes remained. The results speak to a previously unappreciated degree of genetic biodiversity, which we propose to quantify using the birth-event-weighted gene count method.


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