Every sequence has three possible reading frames

KEY TERMS:

• A reading frame is one of the three possible ways of reading a nucleotide sequence. Each reading frame divides the sequence into a series of successive triplets. There are three possible reading frames in any sequence, depending on the starting point. If the first frame starts at position 1, the second frame starts at position 2, and the third frame starts at position 3.
• An open reading frame (ORF) is a sequence of DNA consisting of triplets that can be translated into amino acids starting with an initiation codon and ending with a termination codon.
• The initiation codon is a special codon (usually AUG) used to start synthesis of a protein.
• A stop codon (Termination codon) is one of three triplets (UAG, UAA, UGA) that causes protein synthesis to terminate. They are also known historically as nonsense codons. The UAA codon is called ochre, and the UAA codon is called amber, after the names of the nonsense mutations by which they were originally identified.
• A blocked reading frame cannot be translated into protein because of the occurrence of termination codons.

KEY CONCEPTS:

• Usually only one reading frame is translated and the other two are blocked by frequent termination signals. 

If the genetic code is read in nonoverlapping triplets, there are three possible ways of translating any nucleotide sequence into protein, depending on the starting point. These called reading frames. For the sequence

A C G A C G A C G A C G A C G A C G

the three possible reading frames are

ACG ACG ACG ACG ACG ACG ACG

 CGA CGA CGA CGA CGA CGA CGA

  GAC GAC GAC GAC GAC GAC GAC

A reading frame that consists exclusively of triplets representing amino acids is called an open reading frame or ORF. A sequence that is translated into protein has a reading frame that starts with a special initiation codon (AUG) and that extends through a series of triplets representing amino acids until it ends at one of three types of termination codon (see 5 Messenger RNA).

A reading frame that cannot be read into protein because termination codons occur frequently is said to be blocked. If a sequence is blocked in all three reading frames, it cannot have the function of coding for protein.

When the sequence of a DNA region of unknown function is obtained, each possible reading frame is analyzed to determine whether it is open or blocked. Usually no more than one of the three possible frames of reading is open in any single stretch of DNA. 

Figure 1.34 shows an example of a sequence that can be read in only one reading frame, because the alternative reading frames are blocked by frequent termination codons. A long open reading frame is unlikely to exist by chance; if it were not translated into protein, there would have been no selective pressure to prevent the accumulation of termination codons. So the identification of a lengthy open reading frame is taken to be prima facie evidence that the sequence is translated into protein in that frame. An open reading frame (ORF) for which no protein product has been identified is sometimes called an unidentified reading frame (URF).