Chimera (molecular biology)

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In genetics and molecular biology, a chimera is a single DNA sequence originating from multiple transcripts or parent sequences. It can occur in various contexts. Chimeras are generally considered a contaminant, as a chimera can be interpreted as a novel sequence while it is in fact an artifact. However, the formation of artificial chimeras can also be a useful tool in the molecular biology. For example, in protein engineering, "chimeragenesis (forming chimeras between proteins that are encoded by homologous cDNAs)"[1] is one of the "two major techniques used to manipulate cDNA sequences".[1]

Description[]

Transcript chimera[]

A chimera can occur as a single cDNA sequence originating from two transcripts. It is usually considered to be a contaminant in transcript and expressed sequence tag (which results in the moniker of EST chimera) databases.[2] It is estimated that approximately 1% of all transcripts in the National Center for Biotechnology Information's Unigene database contain a "chimeric sequence".[3]

PCR chimera[]

A chimera can also be an artifact of PCR amplification. It occurs when the extension of an amplicon is aborted, and the aborted product functions as a primer in the next PCR cycle. The aborted product anneals to the wrong template and continues to extend, thereby synthesizing a single sequence sourced from two different templates.[4]

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 inflating over diversity.

Chimeric read[]

A chimeric read is a digital DNA sequence (i.e. a string of letters in a file that can be read as a DNA sequence) that originates from an actual chimera (i.e. a physical DNA sequence in a sample) or produced due to misreading the sample. The latter is known to occur with sequencing of electrophoresis gels.[5]

Some methods have been devised to detect chimeras, like:

  • CHECK_CHIMERA of the Ribosomal Database Project [6]
  • ChimeraSlayer in QIIME[7][4]
  • uchime in usearch[8]
  • removeBimeraDenovo() in dada2[9]
  • Bellerophon[10]
  • CATCh[11]
  • DECIPHER[12]

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."[13]
  • Researchers have created receptor chimeras in their studies of Oncostatin M.

See also[]

References[]

  1. ^ a b Lajtha A, Reith ME (2007). Handbook of Neurochemistry and Molecular Neurobiology Neural Membranes and Transport. Boston, MA: Springer Science+Business Media, LLC. p. 485. ISBN 978-0-387-30347-5. p. 424
  2. ^ Unneberg P, Claverie JM (February 2007). Hoheisel J (ed.). "Tentative mapping of transcription-induced interchromosomal interaction using chimeric EST and mRNA data". PLOS ONE. 2 (2): e254. Bibcode:2007PLoSO...2..254U. doi:10.1371/journal.pone.0000254. PMC 1804257. PMID 17330142. open access
  3. ^ Nelson C. "EST Assembly for the Creation of Oligonucleotide Probe Targets" (PDF). Agilent Technologies. Archived from the original (PDF) on 23 February 2012. Retrieved May 12, 2009.
  4. ^ a b Haas BJ, Gevers D, Earl AM, Feldgarden M, Ward DV, Giannoukos G, et al. (March 2011). "Chimeric 16S rRNA sequence formation and detection in Sanger and 454-pyrosequenced PCR amplicons". Genome Research. 21 (3): 494–504. doi:10.1101/gr.112730.110. PMC 3044863. PMID 21212162.
  5. ^ Porter S (1 February 2007). "Sequencing a Genome, part VI: Chimeras are not just funny-looking animals". ScienceBlogs. Retrieved 2019-01-10.
  6. ^ Maidak BL, Olsen GJ, Larsen N, Overbeek R, McCaughey MJ, Woese CR (January 1996). "The Ribosomal Database Project (RDP)". Nucleic Acids Research. 24 (1): 82–85. doi:10.1093/nar/24.1.82. PMC 145599. PMID 8594608.
  7. ^ "Chimera checking sequences with QIIME". Quantitative Insights Into Microbial Ecology (QIIME). Retrieved 2019-01-10.
  8. ^ Edgar R. "UCHIME algorithm". drive5.com. Retrieved 2019-01-10.
  9. ^ "removeBimeraDenovo function". R Documentation. www.rdocumentation.org. Retrieved 2019-01-10.
  10. ^ Huber T, Faulkner G, Hugenholtz P (September 2004). "Bellerophon: a program to detect chimeric sequences in multiple sequence alignments". Bioinformatics. 20 (14): 2317–2319. doi:10.1093/bioinformatics/bth226. PMID 15073015.
  11. ^ Mysara M, Saeys Y, Leys N, Raes J, Monsieurs P (March 2015). Wommack KE (ed.). "CATCh, an ensemble classifier for chimera detection in 16S rRNA sequencing studies". Applied and Environmental Microbiology. 81 (5): 1573–1584. Bibcode:2015ApEnM..81.1573M. doi:10.1128/AEM.02896-14. PMC 4325141. PMID 25527546.
  12. ^ Wright ES, Yilmaz LS, Noguera DR (February 2012). "DECIPHER, a search-based approach to chimera identification for 16S rRNA sequences". Applied and Environmental Microbiology. 78 (3): 717–725. Bibcode:2012ApEnM..78..717W. doi:10.1128/AEM.06516-11. PMC 3264099. PMID 22101057.
  13. ^ "Entrez Gene: CYP2C18 cytochrome P450, family 2, subfamily C, polypeptide 18". National Center for Biotechnology Information. Retrieved May 12, 2009.
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