Question

In their studies of frameshift mutations, Crick, Barnett, Brenner, and Watts- Tobin found that either three "pluses" or three "minuses" restored the correct reading frame. (a) Assuming the code is a triplet, what effect would the addition or loss of six nucleotides have on the reading frame? (b) If the code were a sextuplet (consisting of six nucleotides), would the reading frame be restored by the addition or loss of three, six, or nine nucleotides?

Short answer

Answer: In a triplet code, the addition or loss of nucleotides in multiples of three (e.g., 6) will maintain the reading frame. In a sextuplet code, the maintenance of the reading frame occurs only when the number of added or lost nucleotides is a multiple of six (e.g., 6).

Step-by-step solution

Understanding Reading Frames

The reading frame is a consecutive sequence of codons, which are groups of three nucleotides that correspond to a specific amino acid. In most cases, the genetic code is a triplet, meaning that each codon consists of three nucleotides.

Part A: Triplet Code - Addition or Loss of Six Nucleotides

Since in a triplet code, the reading frame consists of three nucleotides per codon, adding or subtracting a multiple of three nucleotides will maintain the same reading frame. In this case, we are asked to analyze the effect of adding or subtracting six nucleotides (which is a multiple of three). The reading frame will be maintained, and no frameshift will occur.

Part B: Sextuplet Code - Reading Frame Restoration Possibilities

If the code were a sextuplet (consisting of six nucleotides per codon), the reading frame would require the addition or subtraction of multiples of six nucleotides to maintain the correct reading frame. In this scenario, we examine three possibilities: 1. The addition or loss of three nucleotides (half of a sextuplet codon), which would shift the reading frame but not restore it. 2. The addition or loss of six nucleotides (one full sextuplet codon), which would maintain the correct reading frame and not cause a shift. 3. The addition or loss of nine nucleotides (1.5 times a sextuplet codon), which would also shift the reading frame but not restore it. In conclusion, if the code were a sextuplet, only the addition or loss of six nucleotides would restore the reading frame. The addition or loss of three or nine nucleotides would not restore the correct reading frame.

Key concepts

Genetic Code

The genetic code is the set of rules by which information encoded in genetic material (DNA or RNA sequences) is translated into proteins by living cells. Proteins are made up of amino acids that are assembled in a specific order determined by the sequence of nucleotides in a gene. The genetic code is 'triplet', meaning each set of three nucleotides, known as a codon, corresponds to one amino acid or a stop signal during protein synthesis.

Since there are four different nucleotides, there are a total of 64 possible codons (4 x 4 x 4). Most amino acids are encoded by more than one codon, a feature referred to as the 'redundancy' of the genetic code. This redundancy helps protect against mutations by allowing for some nucleotide changes to occur without altering the protein sequence. Understanding the specificity and redundancy of the genetic code is essential to grasp how changes in DNA can affect protein synthesis and lead to genetic disorders or variability.

Reading Frame

The reading frame is an essential concept in genetics and molecular biology. It refers to the way nucleotides in the DNA or RNA are divided into consecutive, non-overlapping triplets or codons. Each reading frame begins at a specific starting point and continues in groups of three nucleotides until a stop codon is reached, signaling the end of protein synthesis.

A frameshift mutation occurs when nucleotides are added or deleted from the sequence, shifting the grouping of the codons and potentially altering the entire downstream amino acid sequence. This can drastically change the resulting protein's structure and function. As the exercises suggest, for a triplet codon system, adding or subtracting six nucleotides (multiples of three) would keep the reading frame intact. For a sextuplet system, only intervals of six will preserve the frame, unlike in the triplet system, where any multiple of three would suffice.

Nucleotides

Nucleotides are the basic building blocks of nucleic acids, DNA, and RNA. Each nucleotide consists of three components: a sugar molecule (deoxyribose in DNA and ribose in RNA), a phosphate group, and a nitrogenous base. There are four different bases in DNA: adenine (A), cytosine (C), guanine (G), and thymine (T). RNA contains uracil (U) instead of thymine.

Nucleotides are linked together by phosphodiester bonds to form the long strands of DNA and RNA. The sequence of these nucleotides stores the hereditary information of organisms. Mutations such as additions or deletions of nucleotides can lead to changes in the genetic code and may result in genetic diseases or variabilities in traits. As the problem set illustrates, the impact of such changes depends on the structure of the genetic code and can have different consequences on the function of the resulting protein, depending on how they impact the reading frame.