Question

Why is a single base-pair deletion mutation within a protein-coding sequence more likely to be harmful than a single base-pair change mutation?

Short answer

A single base-pair deletion mutation within a protein-coding sequence is more likely to be harmful than a single base-pair change mutation because it can cause a frameshift mutation, significantly altering the amino acid sequence and potentially producing nonfunctional or harmful proteins. In contrast, single base-pair change mutations may have less severe effects due to the redundancy of the genetic code, which can result in silent, missense, or nonsense mutations with varying consequences.

Step-by-step solution

Understand the genetic code and its relationship to protein-coding sequences

In this context, it's important to understand that the genetic code is degenerate, meaning that most amino acids are coded by more than one codon (sets of three nucleotide bases). This degeneration of the genetic code allows for some tolerance to single base-pair changes. However, deletions of nucleotide bases can lead to more dramatic consequences.

Understand point mutations

Point mutations are genetic mutations where a single nucleotide base is changed, inserted, or deleted within the DNA sequence. There are three main types of point mutations: 1. Base substitution: A single nucleotide base is replaced by another. 2. Base insertion: A single nucleotide base is inserted into the sequence. 3. Base deletion: A single nucleotide base is removed from the sequence.

Describe the effects of a single base-pair deletion

A single base-pair deletion within a protein-coding sequence can lead to a frameshift mutation, in which the reading frame of the genetic code is altered. The deletion of a single base-pair shifts all downstream codons by one base, resulting in a completely different amino acid sequence from the point of the deletion onward. This can lead to the production of nonfunctional or even harmful proteins, which can have a severe impact on the organism. Examples of the consequences of a frameshift caused by a single base-pair deletion include Tay-Sachs disease and Cystic Fibrosis, among others.

Describe the effects of a single base-pair change

Comparatively, a single base-pair change mutation often has less dramatic consequences due to the redundancy of the genetic code. A base-pair change may either result in: 1. Silent mutation: The change in the nucleotide does not have any effect on the resulting amino acid, thanks to the degeneracy of the genetic code. 2. Missense mutation: The change results in a different amino acid being incorporated into the protein. The impact of this mutation will depend on the chemical properties and role of the original amino acid versus the new amino acid. Some missense mutations can have minimal effects, while others can be harmful. 3. Nonsense mutation: The change results in a premature STOP codon, often leading to a truncated, nonfunctional protein. This type of mutation can also be harmful.

Compare the potential harm of both mutation types

Considering the redundancy of the genetic code and the various outcomes of a single base-pair change mutation, there is a higher likelihood that it will have a less severe effect on the organism. In contrast, a single base-pair deletion mutation will often cause a frameshift, significantly altering the amino acid sequence, with a greater potential to be harmful. In conclusion, a single base-pair deletion mutation within a protein-coding sequence is more likely to be harmful than a single base-pair change mutation due to the higher probability of causing a frameshift mutation, leading to a severely altered protein.

Key concepts

Genetic Code

The genetic code is the essential dictionary within biology that tells cells how to turn a sequence of nucleotides into a sequence of amino acids—the building blocks of proteins. Imagine it much like a set of instructions for assembling a complex piece of furniture, where the correct sequence of steps leads to the intended product. In this biological set of instructions, every three nucleotides, known as a codon, correspond to a specific amino acid. An important feature of the genetic code is its redundancy; several codons can encode for the same amino acid.

This redundancy provides a buffer against certain mutations, specifically base-pair changes, where one nucleotide is replaced by another. These substitutions might not have a dramatic effect if the new codon still translates into the same amino acid. However, not all changes to the genetic script lead to harmless variations. Deletions, for instance, can be particularly devastating, leading to a complete rewriting of the instructions downstream of the mutation—often with harmful results.

Frameshift Mutation

A frameshift mutation is akin to deleting a letter in a sentence, which shifts the grouping of all subsequent letters and scrambles the intended message. In biological terms, when a base-pair deletion occurs, the nucleotide sequence from the point of deletion is 'read' incorrectly. This means that all codons downstream of the mutation are shifted out of their proper reading frame.

The resulting protein is constructed with an entirely different set of amino acids from the point of mutation onwards, often rendering it nonfunctional or even detrimental to the cell. Frameshift mutations can be caused by either deletions or insertions of nucleotides within the DNA sequence. These types of mutations can lead to severe genetic disorders or even prove lethal, especially if critical proteins are affected.

Base-Pair Deletion

A base-pair deletion is a type of mutation where a single pair of nucleotides is removed from the DNA sequence. This seemingly minor loss can have a cascading effect on a protein's structure and function because it alters the genetic instructions for building that protein.

Since proteins are assembled amino acid by amino acid in a linear fashion based on triplet codons, the deletion of even a single base pair can misalign the entire sequence that follows. The magnitude of this misalignment can lead to the production of proteins with improper shapes or functions, much like removing a single piece from an intricately connected puzzle can prevent the picture from forming correctly. In a protein-coding sequence, this can have dire consequences for the organism if the affected protein plays an essential role in cellular processes.

Protein-Coding Sequence

The segments of DNA that are transcribed and translated to make proteins are termed protein-coding sequences. These sequences are fundamentally important as they define the identity, structure, and function of proteins within the organism. Each segment is a precise linear array of nucleotides that, through the process of translation, dictates the order of amino acids in a protein.

Just as each letter matters in constructing words that make sense in a sentence, each nucleotide is vital in the protein-coding sequence for creating functional proteins. Mutations in these sequences, particularly base-pair deletions, can drastically change the protein 'sentence,' leading to a dysfunctional protein—or in some severe cases, a harmful one. Protein-coding sequences are the core of genetic expression and heredity, and their integrity is crucial for the survival and proper functioning of an organism.