Chimera (molecular biology)

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]

This article is about a single DNA sequence. For other uses, see Chimera.

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. an 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]

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."[11]
  • Researchers have created receptor chimeras in their studies of Oncostatin M.

See also

References
  1. Lajtha, Abel; E. A. Reith, Maarten (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; Hoheisel, Jörg (2007). Hoheisel, Jörg (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.
  3. Charlie Nelson. "EST Assembly for the Creation of Oligonucleotide Probe Targets" (PDF). Agilent Technologies. Retrieved May 12, 2009.
  4. Birren, Bruce W.; Knight, Rob; Petrosino, Joseph F.; Consortium, The Human Microbiome; DeSantis, Todd Z.; Methé, Barbara; Sodergren, Erica; Highlander, Sarah K.; Tabbaa, Diana (2011-03-01). "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. ISSN 1549-5469. PMC 3044863. PMID 21212162.
  5. "Sequencing a Genome, part VI: Chimeras are not just funny-looking animals | ScienceBlogs". scienceblogs.com. Retrieved 2019-01-10.
  6. Maidak, B. (1996). "The Ribosomal Database Project (RDP)". Nucleic Acids Research. 24 (1): 82–85. doi:10.1093/nar/24.1.82. PMC 145599. PMID 8594608. Retrieved May 12, 2009.
  7. "Chimera checking sequences with QIIME — Homepage". qiime.org. Retrieved 2019-01-10.
  8. "UCHIME algorithm". drive5.com. Retrieved 2019-01-10.
  9. "removeBimeraDenovo function | R Documentation". www.rdocumentation.org. Retrieved 2019-01-10.
  10. Hugenholtz, Philip; Faulkner, Geoffrey; Huber, Thomas (2004-09-22). "Bellerophon: a program to detect chimeric sequences in multiple sequence alignments". Bioinformatics. 20 (14): 2317–2319. doi:10.1093/bioinformatics/bth226. ISSN 1367-4803. PMID 15073015.
  11. "Entrez Gene: CYP2C18 cytochrome P450, family 2, subfamily C, polypeptide 18". National Center for Biotechnology Information. Retrieved May 12, 2009.


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