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Miguel.curto (talk | contribs) I have included genomic instability subtitle in leishmania page. The information was obtained from PNAS article that i have cited. |
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''Leishmania'' species produce several different [[heat shock protein]]s. These include Hsp83, a homolog of [[Hsp90]]. A regulatory element in the [[3' UTR]] of Hsp83 controls [[Translation (genetics)|translation]] of Hsp83 in a temperature-sensitive manner. This region forms a stable [[Nucleic acid secondary structure|RNA structure]] which melts at higher temperatures.<ref>{{cite journal|last=David|first=M|author2=Gabdank, I |author3=Ben-David, M |author4=Zilka, A |author5=Orr, I |author6=Barash, D |author7= Shapira, M |title=Preferential translation of Hsp83 in Leishmania requires a thermosensitive polypyrimidine-rich element in the 3' UTR and involves scanning of the 5' UTR.|journal=RNA|date=February 2010|volume=16|issue=2|pages=364–74|pmid=20040590|doi=10.1261/rna.1874710|pmc=2811665}}</ref>
== Genomic instability ==
''Leishmania'' lacks promoter-dependent regulation, so its genomic regulation is at post-transcriptional level through [[Copy number variation|copy number variations (CNV)]] of transcripts, a mechanism capable of controlling the abundance of these transcripts according to the situation in which the organism finds itself. These processes cause a great susceptibility to genomic instability in the parasite. This involves [[Epistasis|epistatic interactions]] between genes, which drive these changes in gene expression, leading to compensatory mechanisms in the ''Leishmania'' genome that result in the adaptive evolution of the parasite.
During the research carried out by Giovanni Bussotti and collaborators at the Pasteur Institute, belonging to the University of Paris, a genome-wide association study ([[Genome-wide association study|GWAS]]) of ''Leishmania donovani'' identified CNVs in 14% of the coding regions and in 4% of the non-coding regions. In addition, an [[Experimental evolution|experimental evolution study (EE Approach)]] was performed on L. donovani amastigotes obtained from clinical cases of hamsters. By extracting these amastigotes from infected organisms and culturing them in vitro for 36 weeks (3800 generations), it was demonstrated how genomic instability in this parasite is capable of adapting to complicated situations, such as in vitro culture.
An 11kb deletion was detected in the gene coding for Ld1S_360735700, a [[NIMA-related kinase 1|NIMA-related kinase]] with key functions in the correct progression of mitosis. With the advancement of in vitro culture generations the loss of the kinase becomes more notorious, decreasing growth rate of the parasite, but the genomic instability of Leishmania manages, through compensatory mechanisms, to attenuate this reduction in growth so that the in vitro culture is maintained. First, as an adaptation of the culture to the loss of this kinase, it was detected an increase in the expression of another orthologous kinase (Ld1S_360735800) whose coding region is adjacent to that of the lost kinase. Secondly, a reduction in the expression of 23 transcripts related to [[Flagellum|flagellar biogenesis]] was observed. So adaptation in Leishmania leads the parasite to eliminate flagellar movement from its needs, since it is not necessary in in vitro culture, preserving the energy invested in this movement to increase the growth rate and compensating the loss of the kinase.
Finally, coamplification of ribosomal protein clusters, [[Ribosomal RNA|ribosomal RNA]] (rRNA), [[Transfer RNA|transfer RNA]] (tRNA) and [[SnoRNA|nucleolar small RNA]] (snoRNA) was observed. Increased expression of these clusters leads to increased ribosomal biogenesis and protein biosynthesis. This is most evident in the case of small nucleolar RNAs (snoRNA), for which amplification of a large cluster of 15 snoRNAs was observed on chromosome 33. The function of these nucleic acids is [[Methylation|methylation]] and inclusion of [[Pseudouridine|pseuouridine]] in ribosomes. In this case, an increase in these modifications was observed in the large subunits of the ribosomes of individuals in culture, specifically in the PTC ([[Peptidyl transferase|peptidyl transferase]] center) and in the mRNA entry tunnel to the ribosome for protein synthesis. These changes lead to an increase in ribosomal biogenesis, resulting in increased protein synthesis and growth rate.
In conclusion, the loss of the kinase is compensated by the genomic instability of ''Leishmania donovani'' by increasing the expression of another orthologous kinase, decreasing flagellar biogenesis and increasing ribosomal biogenesis. These compensations result in the growth rate of the culture being as less affected as possible by the initial loss of the kinase, and the parasite is perfectly adapted to the in vitro culture, which is not its natural habitat.
<ref>{{cite journal |last1=Bussotti |first1=Giovanni |last2=Piel |first2=Laura |last3=Pescher |first3=Pascale |last4=Domagalska |first4=Malgorzata A. |last5=Rajan |first5=K. Shanmugha |last6=Cohen-Chalamish |first6=Smadar |last7=Doniger |first7=Tirza |last8=Hiregange |first8=Disha-Gajanan |last9=Myler |first9=Peter J. |last10=Unger |first10=Ron |last11=Michaeli |first11=Shulamit |last12=Späth |first12=Gerald F. |title=Genome instability drives epistatic adaptation in the human pathogen Leishmania |journal=Proceedings of the National Academy of Sciences |date=21 December 2021 |volume=118 |issue=51 |pages=e2113744118 |doi=10.1073/pnas.2113744118 |url=https://www.pnas.org/doi/10.1073/pnas.2113744118 |language=en |issn=0027-8424}}</ref>
== Sexual reproduction ==
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