-
Something wrong with this record ?
Experimental evolution links post-transcriptional regulation to Leishmania fitness gain
L. Piel, KS. Rajan, G. Bussotti, H. Varet, R. Legendre, C. Proux, T. Douché, Q. Giai-Gianetto, T. Chaze, T. Cokelaer, B. Vojtkova, N. Gordon-Bar, T. Doniger, S. Cohen-Chalamish, P. Rengaraj, C. Besse, A. Boland, J. Sadlova, JF. Deleuze, M....
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
NLK
Directory of Open Access Journals
from 2005
Free Medical Journals
from 2005
Public Library of Science (PLoS)
from 2005
PubMed Central
from 2005
Europe PubMed Central
from 2005
ProQuest Central
from 2005-09-01
Open Access Digital Library
from 2005-09-01
Open Access Digital Library
from 2005-01-01
Open Access Digital Library
from 2005-01-01
Medline Complete (EBSCOhost)
from 2005-09-01
Health & Medicine (ProQuest)
from 2005-09-01
- MeSH
- Leishmania donovani * genetics MeSH
- Leishmaniasis, Visceral * parasitology MeSH
- Humans MeSH
- Genomic Instability MeSH
- Proteomics MeSH
- Gene Expression Regulation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The protozoan parasite Leishmania donovani causes fatal human visceral leishmaniasis in absence of treatment. Genome instability has been recognized as a driver in Leishmania fitness gain in response to environmental change or chemotherapy. How genome instability generates beneficial phenotypes despite potential deleterious gene dosage effects is unknown. Here we address this important open question applying experimental evolution and integrative systems approaches on parasites adapting to in vitro culture. Phenotypic analyses of parasites from early and late stages of culture adaptation revealed an important fitness tradeoff, with selection for accelerated growth in promastigote culture (fitness gain) impairing infectivity (fitness costs). Comparative genomics, transcriptomics and proteomics analyses revealed a complex regulatory network associated with parasite fitness gain, with genome instability causing highly reproducible, gene dosage-independent and -dependent changes. Reduction of flagellar transcripts and increase in coding and non-coding RNAs implicated in ribosomal biogenesis and protein translation were not correlated to dosage changes of the corresponding genes, revealing a gene dosage-independent, post-transcriptional mechanism of regulation. In contrast, abundance of gene products implicated in post-transcriptional regulation itself correlated to corresponding gene dosage changes. Thus, RNA abundance during parasite adaptation is controled by direct and indirect gene dosage changes. We correlated differential expression of small nucleolar RNAs (snoRNAs) with changes in rRNA modification, providing first evidence that Leishmania fitness gain in culture may be controlled by post-transcriptional and epitranscriptomic regulation. Our findings propose a novel model for Leishmania fitness gain in culture, where differential regulation of mRNA stability and the generation of modified ribosomes may potentially filter deleterious from beneficial gene dosage effects and provide proteomic robustness to genetically heterogenous, adapting parasite populations. This model challenges the current, genome-centric approach to Leishmania epidemiology and identifies the Leishmania transcriptome and non-coding small RNome as potential novel sources for the discovery of biomarkers that may be associated with parasite phenotypic adaptation in clinical settings.
Department of Parasitology Faculty of Science Charles University Prague Czech Republic
Institut Pasteur Biomics Paris France
Institut Pasteur UTechS MSBio Paris France
Université Paris Saclay CEA Centre National de Recherche en Génomique Humaine Evry France
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc22019174
- 003
- CZ-PrNML
- 005
- 20220804135416.0
- 007
- ta
- 008
- 220720s2022 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1371/journal.ppat.1010375 $2 doi
- 035 __
- $a (PubMed)35294501
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Piel, Laura $u Institut Pasteur, Université de Paris, INSERM U1201, Unité de Parasitologie moléculaire et Signalisation, Paris, France
- 245 10
- $a Experimental evolution links post-transcriptional regulation to Leishmania fitness gain / $c L. Piel, KS. Rajan, G. Bussotti, H. Varet, R. Legendre, C. Proux, T. Douché, Q. Giai-Gianetto, T. Chaze, T. Cokelaer, B. Vojtkova, N. Gordon-Bar, T. Doniger, S. Cohen-Chalamish, P. Rengaraj, C. Besse, A. Boland, J. Sadlova, JF. Deleuze, M. Matondo, R. Unger, P. Volf, S. Michaeli, P. Pescher, GF. Späth
- 520 9_
- $a The protozoan parasite Leishmania donovani causes fatal human visceral leishmaniasis in absence of treatment. Genome instability has been recognized as a driver in Leishmania fitness gain in response to environmental change or chemotherapy. How genome instability generates beneficial phenotypes despite potential deleterious gene dosage effects is unknown. Here we address this important open question applying experimental evolution and integrative systems approaches on parasites adapting to in vitro culture. Phenotypic analyses of parasites from early and late stages of culture adaptation revealed an important fitness tradeoff, with selection for accelerated growth in promastigote culture (fitness gain) impairing infectivity (fitness costs). Comparative genomics, transcriptomics and proteomics analyses revealed a complex regulatory network associated with parasite fitness gain, with genome instability causing highly reproducible, gene dosage-independent and -dependent changes. Reduction of flagellar transcripts and increase in coding and non-coding RNAs implicated in ribosomal biogenesis and protein translation were not correlated to dosage changes of the corresponding genes, revealing a gene dosage-independent, post-transcriptional mechanism of regulation. In contrast, abundance of gene products implicated in post-transcriptional regulation itself correlated to corresponding gene dosage changes. Thus, RNA abundance during parasite adaptation is controled by direct and indirect gene dosage changes. We correlated differential expression of small nucleolar RNAs (snoRNAs) with changes in rRNA modification, providing first evidence that Leishmania fitness gain in culture may be controlled by post-transcriptional and epitranscriptomic regulation. Our findings propose a novel model for Leishmania fitness gain in culture, where differential regulation of mRNA stability and the generation of modified ribosomes may potentially filter deleterious from beneficial gene dosage effects and provide proteomic robustness to genetically heterogenous, adapting parasite populations. This model challenges the current, genome-centric approach to Leishmania epidemiology and identifies the Leishmania transcriptome and non-coding small RNome as potential novel sources for the discovery of biomarkers that may be associated with parasite phenotypic adaptation in clinical settings.
- 650 _2
- $a regulace genové exprese $7 D005786
- 650 _2
- $a nestabilita genomu $7 D042822
- 650 _2
- $a lidé $7 D006801
- 650 12
- $a Leishmania donovani $x genetika $7 D007893
- 650 12
- $a leishmanióza viscerální $x parazitologie $7 D007898
- 650 _2
- $a proteomika $7 D040901
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Rajan, K Shanmugha $u The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan, Israel
- 700 1_
- $a Bussotti, Giovanni $u Institut Pasteur, Université de Paris, INSERM U1201, Unité de Parasitologie moléculaire et Signalisation, Paris, France $u Institut Pasteur, Bioinformatics and Biostatistics Hub, Department of Computational Biology, USR 3756 IP CNRS, Paris, France
- 700 1_
- $a Varet, Hugo $u Institut Pasteur, Bioinformatics and Biostatistics Hub, Department of Computational Biology, USR 3756 IP CNRS, Paris, France $u Institut Pasteur, Biomics, Paris, France; Institut Pasteur, UTechS MSBio, Paris, France
- 700 1_
- $a Legendre, Rachel $u Institut Pasteur, Bioinformatics and Biostatistics Hub, Department of Computational Biology, USR 3756 IP CNRS, Paris, France $u Institut Pasteur, Biomics, Paris, France; Institut Pasteur, UTechS MSBio, Paris, France
- 700 1_
- $a Proux, Caroline $u Institut Pasteur, Biomics, Paris, France; Institut Pasteur, UTechS MSBio, Paris, France
- 700 1_
- $a Douché, Thibaut $u Institut Pasteur, Proteomics Platform Mass Spectrometry for Biology UTechS, C2RT, USR2000 CNRS, Paris, France
- 700 1_
- $a Giai-Gianetto, Quentin $u Institut Pasteur, Bioinformatics and Biostatistics Hub, Department of Computational Biology, USR 3756 IP CNRS, Paris, France $u Institut Pasteur, Proteomics Platform Mass Spectrometry for Biology UTechS, C2RT, USR2000 CNRS, Paris, France
- 700 1_
- $a Chaze, Thibault $u Institut Pasteur, Proteomics Platform Mass Spectrometry for Biology UTechS, C2RT, USR2000 CNRS, Paris, France
- 700 1_
- $a Cokelaer, Thomas $u Institut Pasteur, Bioinformatics and Biostatistics Hub, Department of Computational Biology, USR 3756 IP CNRS, Paris, France $u Institut Pasteur, Biomics, Paris, France; Institut Pasteur, UTechS MSBio, Paris, France
- 700 1_
- $a Vojtkova, Barbora $u Department of Parasitology, Faculty of Science, Charles University, Prague, Czech Republic
- 700 1_
- $a Gordon-Bar, Nadav $u The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan, Israel
- 700 1_
- $a Doniger, Tirza $u The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan, Israel
- 700 1_
- $a Cohen-Chalamish, Smadar $u The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan, Israel
- 700 1_
- $a Rengaraj, Praveenkumar $u The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan, Israel
- 700 1_
- $a Besse, Céline $u Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, Evry, France
- 700 1_
- $a Boland, Anne $u Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, Evry, France
- 700 1_
- $a Sadlova, Jovana $u Department of Parasitology, Faculty of Science, Charles University, Prague, Czech Republic
- 700 1_
- $a Deleuze, Jean-François $u Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, Evry, France
- 700 1_
- $a Matondo, Mariette $u Institut Pasteur, Proteomics Platform Mass Spectrometry for Biology UTechS, C2RT, USR2000 CNRS, Paris, France
- 700 1_
- $a Unger, Ron $u The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan, Israel
- 700 1_
- $a Volf, Petr $u Department of Parasitology, Faculty of Science, Charles University, Prague, Czech Republic
- 700 1_
- $a Michaeli, Shulamit $u The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan, Israel
- 700 1_
- $a Pescher, Pascale $u Institut Pasteur, Université de Paris, INSERM U1201, Unité de Parasitologie moléculaire et Signalisation, Paris, France $1 https://orcid.org/0000000327967855
- 700 1_
- $a Späth, Gerald F $u Institut Pasteur, Université de Paris, INSERM U1201, Unité de Parasitologie moléculaire et Signalisation, Paris, France $1 https://orcid.org/0000000202562029
- 773 0_
- $w MED00008922 $t PLoS pathogens $x 1553-7374 $g Roč. 18, č. 3 (2022), s. e1010375
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/35294501 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y p $z 0
- 990 __
- $a 20220720 $b ABA008
- 991 __
- $a 20220804135410 $b ABA008
- 999 __
- $a ok $b bmc $g 1822674 $s 1170417
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2022 $b 18 $c 3 $d e1010375 $e 20220316 $i 1553-7374 $m PLOS pathogens $n PLoS Pathog $x MED00008922
- LZP __
- $a Pubmed-20220720