Просмотр кода страницы Chimera (molecular biology)

{{short description|Single nucleic acid sequence created from fragments that are normally separated}}
{{About|a single DNA sequence |other uses|Chimera (disambiguation){{!}}Chimera}}
In [[molecular biology]], and more importantly [[DNA sequencing|high-throughput DNA sequencing]], a '''chimera''' is a single DNA sequence originating when multiple [[Transcription (biology)|transcripts]] or DNA sequences get joined. Chimeras can be considered [[Artifact (error)|artifacts]] and be filtered out from the data during processing <ref name=":0">{{Cite web |title=Chimeras |url=https://www.drive5.com/usearch/manual/chimeras.html |access-date=2022-10-27 |website=www.drive5.com |language=en}}</ref> to prevent spurious inferences of biological variation.<ref>{{Cite journal |last=Edgar |first=Robert C. |date=2016-09-12 |title=UCHIME2: improved chimera prediction for amplicon sequencing|website=BioRXiv|publisher=Cold Spring Harbor Laboratory|url=https://www.biorxiv.org/content/10.1101/074252v1 |language=en |article-number=074252 |doi=10.1101/074252|s2cid=88955007 }}</ref> However, chimeras should not be confused with chimeric [[Read (biology)|reads]], which are generally used by structural variant callers to detect [[structural variation]] events<ref name=":1">{{Cite journal |last1=Kosugi |first1=Shunichi |last2=Momozawa |first2=Yukihide |last3=Liu |first3=Xiaoxi |last4=Terao |first4=Chikashi |last5=Kubo |first5=Michiaki |last6=Kamatani |first6=Yoichiro |date=December 2019 |title=Comprehensive evaluation of structural variation detection algorithms for whole genome sequencing |journal=Genome Biology |language=en |volume=20 |issue=1 |page=117 |doi=10.1186/s13059-019-1720-5 |pmid=31159850 |pmc=6547561 |issn=1474-760X |doi-access=free }}</ref> and are not always an indication of the presence of a chimeric transcript or gene.

In a different context, the deliberate creation of artificial chimeras can also be a useful tool in molecular biology. For example, in [[protein engineering]], "chimeragenesis" (forming chimeras between proteins that are encoded by homologous [[Complementary DNA|cDNAs]])<ref name="Handbook">{{cite book |title=Handbook of Neurochemistry and Molecular Neurobiology Neural Membranes and Transport | vauthors = Lajtha A, Reith ME |publisher=Springer Science+Business Media, LLC. |year=2007 | isbn = 978-0-387-30347-5 |location=Boston, MA |page=485 }} p. 424</ref> is one of the "two major techniques used to manipulate cDNA sequences".<ref name="Handbook" /> For gene fusions that occur through natural processes, see [[Chimeric gene|chimeric genes]] and [[Fusion gene|fusion genes]].

== Description ==

=== Transcript chimera ===
A chimera can occur as a single [[cDNA]] sequence originating from two [[Transcription (genetics)|transcripts]]. It is usually considered to be a contaminant in transcript and [[expressed sequence tag]] (which results in the moniker of '''EST chimera''') databases.<ref>{{cite journal | vauthors = Unneberg P, Claverie JM | title = Tentative mapping of transcription-induced interchromosomal interaction using chimeric EST and mRNA data | journal = PLOS ONE | volume = 2 | issue = 2 | article-number = e254 | date = February 2007 | pmid = 17330142 | pmc = 1804257 | doi = 10.1371/journal.pone.0000254 | veditors = Hoheisel J | doi-access = free | bibcode = 2007PLoSO...2..254U }} {{open access}}</ref> It is estimated that approximately 1% of all transcripts in the [[National Center for Biotechnology Information]]'s Unigene database contain a "chimeric sequence".<ref>{{cite web |url= http://www.chem.agilent.com/Library/applications/5989_0750_EST_final72.pdf | archive-url = https://web.archive.org/web/20120223155430/http://www.chem.agilent.com/Library/applications/5989_0750_EST_final72.pdf | archive-date = 23 February 2012 |title=EST Assembly for the Creation of Oligonucleotide Probe Targets | vauthors = Nelson C |publisher=[[Agilent Technologies]] |access-date=May 12, 2009}}</ref>

=== PCR chimera ===
A chimera can also be an artifact of [[Polymerase chain reaction|PCR]] amplification. It occurs when the extension of an [[amplicon]] is aborted, and the aborted product functions as a [[Primer (molecular biology)|primer]] in the next PCR cycle. The aborted product [[Annealing (biology)|anneals]] to the wrong template and continues to extend, thereby synthesizing a single sequence sourced from two different templates.<ref name="Birren 494–504">{{cite journal | vauthors = Haas BJ, Gevers D, Earl AM, Feldgarden M, Ward DV, Giannoukos G, Ciulla D, Tabbaa D, Highlander SK, Sodergren E, Methé B, DeSantis TZ, Petrosino JF, Knight R, Birren BW | display-authors = 6 | title = Chimeric 16S rRNA sequence formation and detection in Sanger and 454-pyrosequenced PCR amplicons | journal = Genome Research | volume = 21 | issue = 3 | pages = 494–504 | date = March 2011 | pmid = 21212162 | pmc = 3044863 | doi = 10.1101/gr.112730.110 }}</ref>

PCR chimeras are an important issue to take into account during [[metabarcoding]], where DNA sequences from environmental samples are used to determine biodiversity. A chimera is a novel sequence that will most probably not match to any known organism. Hence, it might be interpreted as a new species thereby overinflating the diversity.

PCR chimeras also occur in DNA sequencing. In this case, the most common mechanism of chimera formation is that incomplete extension during the PCR results in partial sequence strands that can act as primers in subsequent PCR cycles on similar but non identical sequences. Extension of such hybrid priming events causes the formation of chimeric sequences.<ref name=":0" />

Some computational methods have been devised to detect and remove chimeras, like:

* CHECK_CHIMERA of the Ribosomal Database Project <ref>{{cite journal |vauthors=Maidak BL, Olsen GJ, Larsen N, Overbeek R, McCaughey MJ, Woese CR |date=January 1996 |title=The Ribosomal Database Project (RDP) |journal=Nucleic Acids Research |volume=24 |issue=1 |pages=82–85 |doi=10.1093/nar/24.1.82 |pmc=145599 |pmid=8594608}}</ref> 
* ChimeraSlayer in QIIME<ref>{{Cite web |title=Chimera checking sequences with QIIME |url=http://qiime.org/tutorials/chimera_checking.html |access-date=2019-01-10 |work=Quantitative Insights Into Microbial Ecology (QIIME)}}</ref><ref name="Birren 494–504" />
* {{proper name|uchime}} in {{proper name|usearch}}<ref>{{Cite web |title=UCHIME algorithm |url=http://drive5.com/usearch/manual/uchime_algo.html |access-date=2019-01-10 |website=drive5.com |vauthors=Edgar R}}</ref>
* removeBimeraDenovo() in dada2<ref>{{Cite web |title=removeBimeraDenovo function |url=https://www.rdocumentation.org/packages/dada2/versions/1.0.3/topics/removeBimeraDenovo |access-date=2019-01-10 |work=R Documentation |publisher=www.rdocumentation.org}}</ref> 
* Bellerophon<ref>{{cite journal |vauthors=Huber T, Faulkner G, Hugenholtz P |date=September 2004 |title=Bellerophon: a program to detect chimeric sequences in multiple sequence alignments |journal=Bioinformatics |volume=20 |issue=14 |pages=2317–2319 |doi=10.1093/bioinformatics/bth226 |pmid=15073015 |doi-access=free}}</ref>
* CATCh<ref>{{cite journal |vauthors=Mysara M, Saeys Y, Leys N, Raes J, Monsieurs P |date=March 2015 |title=CATCh, an ensemble classifier for chimera detection in 16S rRNA sequencing studies |journal=Applied and Environmental Microbiology |volume=81 |issue=5 |pages=1573–1584 |bibcode=2015ApEnM..81.1573M |doi=10.1128/AEM.02896-14 |pmc=4325141 |pmid=25527546 |veditors=Wommack KE}}</ref>
* DECIPHER<ref>{{cite journal |vauthors=Wright ES, Yilmaz LS, Noguera DR |date=February 2012 |title=DECIPHER, a search-based approach to chimera identification for 16S rRNA sequences |journal=Applied and Environmental Microbiology |volume=78 |issue=3 |pages=717–725 |bibcode=2012ApEnM..78..717W |doi=10.1128/AEM.06516-11 |pmc=3264099 |pmid=22101057}}</ref>

=== Chimeric read ===
A read is a sequence of nucleic acids determined through high-throughput DNA or RNA sequencing, corresponding to a DNA or RNA fragment. A chimeric read or split read means that multiple subsections of that read [[Sequence alignment|align]] to different positions in a [[reference genome]].<ref>{{Cite web |title=SAM Format specifications |url=https://samtools.github.io/hts-specs/SAMv1.pdf |access-date=2023-05-31}}</ref> They are not always a sign of the presence of a PCR chimera and often used to detect [[Structural variation|structural variations]].<ref name=":1" />

== Examples ==
* "The first mRNA transcript isolated for..." the human gene [[C2orf3]] "...was part of an artificial chimera..."
* CYP2C17 was thought to be a human gene, but "...is now considered an artefact based on a chimera of [[CYP2C18]] and CYP2C19."<ref>{{cite web | title=Entrez Gene: CYP2C18 cytochrome P450, family 2, subfamily C, polypeptide 18| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=1562 |publisher=[[National Center for Biotechnology Information]] |access-date=May 12, 2009}}</ref>
* Researchers have created receptor chimeras in their studies of [[Oncostatin M]].

== See also ==
{{Portal|Biology}}
* [[Ribosome]]
* [[Transgene]]
* [[Trans-splicing]]
* [[Chimera (genetics)]]
* [[chimeric gene]]
* [[fusion gene]]
{{Clear}}

== References ==
{{Reflist|30em}}

[[Category:Genetics]]