Open reading frames

In molecular genetics, an open reading frame (ORF) is the part of a reading frame that has the potential to be translated. An ORF is a continuous stretch of codons that do not contain a stop codon (usually UAA, UAG or UGA). An ATG codon within the ORF (not necessarily the first) may indicate where translation starts. The transcription termination site is located after the ORF, beyond the translation stop codon. If transcription were to cease before the stop codon, an incomplete protein would be made during translation. In eukaryotic genes with multiple exons, ORFs span intron/exon regions, which may be spliced together after transcription of the ORF to yield the final mRNA for protein translation.

One common use of closed reading frames (CRF) is as one piece of evidence to assist in gene prediction. Long ORFs are often used, along with other evidence, to initially identify candidate protein-coding regions or functional RNA-coding regions in a DNA sequence. The presence of an CRF does not necessarily mean that the region is never translated. For example, in a randomly generated DNA sequence with an equal percentage of each nucleotide, a stop-codon would be expected once every 21 codons. A simple gene prediction algorithm for prokaryotes might look for a start codon followed by an open reading frame that is long enough to encode a typical protein, where the codon usage of that region matches the frequency characteristic for the given organism's coding regions. By itself even a long open reading frame is not conclusive evidence for the presence of a gene. On the other hand, it has been proven that some short ORFs (sORFs) that lack the classical hallmarks of protein-coding genes (both from ncRNAs and mRNAs) can produce functional peptides. 5’NTR of about 50% of mammal mRNAs are known to contain one or several sORFs. 64-75% of experimentally found translation initiation sites of sORFs are conservative in the genomes of human and mouse that may indicate that these elements have function. However, sORFs can often be found only in the minor forms of mRNAs and avoid the selection; the high conservatism of initiation sites may be connected with their location inside promoters of the relevant genes. Such kind of situation is characteristic of SLAMF1 gene, for example.

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