Leishmania: Responding to environmental signals and challenges without regulated transcription

Grünebast, Janne; Clos, Joachim

doi:10.1016/j.csbj.2020.11.058

Cited by 18 publications

(18 citation statements)

References 112 publications

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“…Indeed, aneuploidies have been widely reported in natural T. cruzi populations, and although CCNV varies among and within DTUs, it seems constant within a given population ( Schwabl et al, 2019 ; Reis-Cunha et al, 2015 ; Reis-Cunha et al, 2018 ). While in many multicellular organisms, aneuploidy is known to have severe consequences, in trypanosomatids it represents an important mechanism for rapidly overcoming environmental diversity ( Reis-Cunha et al, 2018 ; Prieto Barja et al, 2017 ; Bussotti et al, 2018 ; Grünebast and Clos, 2020 ). Aneuploidy is reversed quickly once the benefits of an extra chromosome expire, as observed in P2 aneuploidies in chromosomes 2 and 21.…”

Section: Discussionmentioning

confidence: 99%

Microevolution of Trypanosoma cruzi reveals hybridization and clonal mechanisms driving rapid genome diversification

Matos

Andersson

2022

eLife

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Protozoa and fungi are known to have extraordinarily diverse mechanisms of genetic exchange. However, the presence and epidemiological relevance of genetic exchange in Trypanosoma cruzi, the agent of Chagas disease, has been controversial and debated for many years. Field studies have identified both predominantly clonal and sexually recombining natural populations. Two of six natural T. cruzi lineages (TcV and TcVI) show hybrid mosaicism, using analysis of single-gene locus markers. The formation of hybrid strains in vitro has been achieved and this provides a framework to study the mechanisms and adaptive significance of genetic exchange. Using whole genome sequencing of a set of experimental hybrids strains, we have confirmed that hybrid formation initially results in tetraploid parasites. The hybrid progeny showed novel mutations that were not attributable to either (diploid) parent showing an increase in amino acid changes. In long-term culture, up to 800 generations, there was a variable but gradual erosion of progeny genomes towards triploidy, yet retention of elevated copy number was observed at several core housekeeping loci. Our findings indicate hybrid formation by fusion of diploid T. cruzi, followed by sporadic genome erosion, but with substantial potential for adaptive evolution, as has been described as a genetic feature of other organisms, such as some fungi.

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Section: Discussionmentioning

confidence: 99%

Microevolution of Trypanosoma cruzi reveals hybridization and clonal mechanisms driving rapid genome diversification

Matos

Andersson

2022

eLife

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“…Indeed, aneuploidies have been widely reported in natural T. cruzi populations, and although CCNV varies among and within DTUs, it seems constant within a given population 13,31,36 . While in many multicellular organisms, aneuploidy is known to have severe consequences, in trypanosomatids it represents an important mechanism for rapidly overcoming environmental diversity [36][37][38][39] . Aneuploidy is reversed quickly once the benefits of an extra chromosome expire, as observed in P2 aneuploidies in chromosomes 2 and 21.…”

Section: Discussionmentioning

confidence: 99%

Experimental microevolution of Trypanosoma cruzi reveals hybridization and clonal mechanisms driving rapid diversification of genome sequence and structure

Matos

Lewis

Talavera-López

et al. 2021

Preprint

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Protozoa and fungi are known to have extraordinarily diverse mechanisms of genetic exchange. However, the presence and epidemiological relevance of genetic exchange in Trypanosoma cruzi, the agent of Chagas disease, has been controversial and debated for many years. Field studies have identified both predominantly clonal and sexually recombining natural populations. Two of six natural T. cruzi lineages (TcV and TcVI) show hybrid mosaicism, using analysis of single-gene locus markers. The formation of hybrid strains in vitro has been achieved and this provides a framework to study the mechanisms and adaptive significance of genetic exchange. Using whole genome sequencing of a set of experimental hybrids strains, we have confirmed that hybrid formation initially results in tetraploid parasites. The hybrid progeny showed novel mutations that were not attributable to either (diploid) parent showing an increase in amino acid changes. In long-term culture, up to 800 generations, there was progressive, gradual erosion of progeny genomes towards triploidy, yet retention of elevated copy number was observed at several core housekeeping loci. Our findings indicate hybrid formation by fusion of diploid T. cruzi, followed by sporadic genome erosion, but with substantial potential for adaptive evolution, as has been described as a genetic feature of other organisms, such as some fungi.

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“…Transcription termination occurs at the end of each polycistronic transcription unit and is determined by the presence of the base J ( van Luenen et al., 2012 ; Reynolds et al., 2016 ; Kieft et al., 2020 ). However, it is commonly stated in the literature that in the absence of transcriptional regulation, the regulation of protein expression in these parasites is mediated by post-transcriptional events, such as RNA degradation, translation control, and protein degradation ( Clayton and Shapira, 2007 ; Grünebast and Clos, 2020 ; Karamysheva et al., 2020 ). Several studies have shown that chromosomal copy number can be associated with transcription levels, supporting the notion that expression control occurs after transcription ( Dumetz et al., 2017 ; Iantorno et al., 2017 ; Patino et al., 2019 ).…”

Section: The Genome Of Leishmania Is Atypicalmentioning

confidence: 99%

Impact of Genetic Diversity and Genome Plasticity of Leishmania spp. in Treatment and the Search for Novel Chemotherapeutic Targets

Santi

Murta

2022

Front. Cell. Infect. Microbiol.

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Leishmaniasis is one of the major public health concerns in Latin America, Africa, Asia, and Europe. The absence of vaccines for human use and the lack of effective vector control programs make chemotherapy the main strategy to control all forms of the disease. However, the high toxicity of available drugs, limited choice of therapeutic agents, and occurrence of drug-resistant parasite strains are the main challenges related to chemotherapy. Currently, only a small number of drugs are available for leishmaniasis treatment, including pentavalent antimonials (SbV), amphotericin B and its formulations, miltefosine, paromomycin sulphate, and pentamidine isethionate. In addition to drug toxicity, therapeutic failure of leishmaniasis is a serious concern. The occurrence of drug-resistant parasites is one of the causes of therapeutic failure and is closely related to the diversity of parasites in this genus. Owing to the enormous plasticity of the genome, resistance can occur by altering different metabolic pathways, demonstrating that resistance mechanisms are multifactorial and extremely complex. Genetic variability and genome plasticity cause not only the available drugs to have limitations, but also make the search for new drugs challenging. Here, we examined the biological characteristics of parasites that hinder drug discovery.

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Leishmania: Responding to environmental signals and challenges without regulated transcription

Cited by 18 publications

References 112 publications

Microevolution of Trypanosoma cruzi reveals hybridization and clonal mechanisms driving rapid genome diversification

Microevolution of Trypanosoma cruzi reveals hybridization and clonal mechanisms driving rapid genome diversification

Experimental microevolution of Trypanosoma cruzi reveals hybridization and clonal mechanisms driving rapid diversification of genome sequence and structure

Impact of Genetic Diversity and Genome Plasticity of Leishmania spp. in Treatment and the Search for Novel Chemotherapeutic Targets

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