molecular biology Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...

, and more importantly high-throughput DNA sequencing, a chimera is a single DNA sequence originating when multiple transcripts or DNA sequences get joined. Chimeras can be considered artifacts and be filtered out from the data during processing to prevent spurious inferences of biological variation. However, chimeras should not be confused with chimeric reads, which are generally used by structural variant callers to detect

structural variation Genomic structural variation is the variation in structure of an organism's chromosome, such as deletions, duplications, copy-number variants, insertions, inversions and translocations. Originally, a structure variation affects a sequence length a ...

events 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 Protein engineering is the process of developing useful or valuable proteins through the design and production of unnatural polypeptides, often by altering amino acid sequences found in nature. It is a young discipline, with much research taking pl ...

, "chimeragenesis" (forming chimeras between proteins that are encoded by homologous cDNAs) p. 424 is one of the "two major techniques used to manipulate cDNA sequences". For gene fusions that occur through natural processes, see chimeric genes and

fusion genes In genetics, a fusion gene is a hybrid gene formed from two previously independent genes. It can occur as a result of translocation, interstitial deletion, or chromosomal inversion. Fusion genes have been found to be prevalent in all main types o ...

Description

Transcript chimera

A chimera can occur as a single

cDNA In genetics, complementary DNA (cDNA) is DNA that was reverse transcribed (via reverse transcriptase) from an RNA (e.g., messenger RNA or microRNA). cDNA exists in both single-stranded and double-stranded forms and in both natural and engin ...

sequence originating from two transcripts. It is usually considered to be a contaminant in transcript and

expressed sequence tag In genetics, an expressed sequence tag (EST) is a short sub-sequence of a cDNA sequence. ESTs may be used to identify gene transcripts, and were instrumental in gene discovery and in gene-sequence determination. The identification of ESTs has pro ...

(which results in the moniker of EST chimera) databases. It is estimated that approximately 1% of all transcripts in the

National Center for Biotechnology Information The National Center for Biotechnology Information (NCBI) is part of the National Library of Medicine (NLM), a branch of the National Institutes of Health (NIH). It is approved and funded by the government of the United States. The NCBI is lo ...

's Unigene database contain a "chimeric sequence".

PCR chimera

A chimera can also be an artifact of PCR amplification. It occurs when the extension of an

amplicon In molecular biology, an amplicon is a piece of DNA or RNA that is the source and/or product of amplification or replication events. It can be formed artificially, using various methods including polymerase chain reactions (PCR) or ligase chain ...

is aborted, and the aborted product functions as a

primer Primer may refer to: Arts, entertainment, and media Films * ''Primer'' (film), a 2004 feature film written and directed by Shane Carruth * ''Primer'' (video), a documentary about the funk band Living Colour Literature * Primer (textbook), a te ...

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. PCR chimeras are an important issue to take into account during

metabarcoding Metabarcoding is the DNA barcoding, barcoding of DNA/RNA (or Environmental DNA, eDNA/Environmental DNA, eRNA) in a manner that allows for the simultaneous identification of many taxa within the same sample. The main difference between barcodin ...

, 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. Some computational methods have been devised to detect and remove chimeras, like: * CHECK_CHIMERA of the Ribosomal Database Project * ChimeraSlayer in QIIME * in * removeBimeraDenovo() in dada2 * Bellerophon * CATCh * DECIPHER

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 align to different positions in a

reference genome A reference genome (also known as a reference assembly) is a digital nucleic acid sequence database, assembled by scientists as a representative example of the genome, set of genes in one idealized individual organism of a species. As they are a ...

. They are not always a sign of the presence of a PCR chimera and often used to detect structural variations.

Examples

* "The first mRNA transcript isolated for..." the human gene

C2orf3 GC-rich sequence DNA-binding factor is a protein that in humans is encoded by the ''GCFC2'' gene. The first mRNA transcript isolated for this gene was part of an artificial chimera derived from two distinct gene transcripts and a primer used in ...

"...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 Cytochrome P450 2C18 is a protein that in humans is encoded by the ''CYP2C18'' gene. Function This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactio ...

and CYP2C19." * Researchers have created receptor chimeras in their studies of

Oncostatin M Oncostatin M, also known as OSM, is a protein that in humans is encoded by the ''OSM'' gene. OSM is a pleiotropic cytokine that belongs to the interleukin 6 group of cytokines. Of these cytokines it most closely resembles leukemia inhibitory f ...

References