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In: Biology

Describe how a single nucleotide insertion in the coding sequence of a gene would affect the...

Describe how a single nucleotide insertion in the coding sequence of a gene would affect the production of the protein (polypeptide) the gene encodes.

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Expert Solution

Point mutations may have a wide range of effects on protein function . As a consequence of the degeneracy of the genetic code, a point mutation will commonly result in the same amino acid being incorporated into the resulting polypeptide despite the sequence change. This change would have no effect on the protein’s structure, and is thus called a silent mutation. A missense mutation results in a different amino acid being incorporated into the resulting polypeptide. The effect of a missense mutation depends on how chemically different the new amino acid is from the wild-type amino acid. The location of the changed amino acid within the protein also is important. For example, if the changed amino acid is part of the enzyme’s active site, then the effect of the missense mutation may be significant. Many missense mutations result in proteins that are still functional, at least to some degree. Sometimes the effects of missense mutations may be only apparent under certain environmental conditions; such missense mutations are called conditional mutations. Rarely, a missense mutation may be beneficial. Under the right environmental conditions, this type of mutation may give the organism that harbors it a selective advantage. Yet another type of point mutation, called a nonsense mutation, converts a codon encoding an amino acid (a sense codon) into a stop codon (a nonsense codon). Nonsense mutations result in the synthesis of proteins that are shorter than the wild type and typically not functional.

Deletions and insertions also cause various effects. Because codons are triplets of nucleotides, insertions or deletions in groups of three nucleotides may lead to the insertion or deletion of one or more amino acids and may not cause significant effects on the resulting protein’s functionality. However, frameshift mutations, caused by insertions or deletions of a number of nucleotides that are not a multiple of three are extremely problematic because a shift in the reading frame results (Figure 1). Because ribosomes read the mRNA in triplet codons, frameshift mutations can change every amino acid after the point of the mutation. The new reading frame may also include a stop codon before the end of the coding sequence. Consequently, proteins made from genes containing frameshift mutations are nearly always nonfunctional.

Insertions are mutations in which extra base pairs are inserted into a new place in the DNA. The number of base pairs inserted can range from one to thousands!

Example of Insertion Mutation: Huntington's disease and the fragile X syndrome are examples of insertion mutation wherein trinucleotide repeats are inserted into the DNA sequence leading to these diseases.

Protein-coding DNA is divided into codons which are three bases long, insertions and deletions in these codons can completely change a gene so its message cannot be decoded correctly. Such mutations are called frameshift mutations. For example, consider the sentence, "The cat ate her rat." Each word represents a codon. If we delete the first letter and read the sentence in the same way, it doesn't make sense. Similarly if the codons become jumbled up, they would no longer make any sense, in such frameshifts, a similar error occurs at the DNA level, where the codons cannot be parsed correctly. This usually gives rise to truncated proteins that are as useless as "rca tet hce tee" is uninformative.

Examples of Frameshift Mutation: Tay-Sachs Disease, Cancers of many types, Crohn's Disease, cystic fibrosis have been associated with Frameshift Mutation.


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