Tuesday, 29 October 2019

Types of mutations in genetics

Types of mutations in genetics

Point mutations

Point mutations

There are many ways in which the structure of the genetic material may in changes. Much of the basis of genetics has been established using simple mutations (point mutations) in which the sequence of the DNA has been altered at a single position. Where this change consists of replacing one nucleotide by another, it is known as a base substitution. The consequence of such a change depends both on the nature of the change and its location. If the changes are within the coding region of a gene (i.e. the region which ultimately is translated into protein), it may cause an alteration of the amino acid sequence which may affect the function of the protein. The alteration may, of course, have a little or no effect, either because the changed triplet still codes for the same amino acid or because the new amino acid is sufficiently similar to the original for the function of the protein to remain unaffected.

For example, the triplet UUA codes for leucine; a single base change in the DNA can give rise to one of nine other codons as shown in Figure.1.

Types of mutations in genetics

Figure .1. Codons arising by single base substitutions from UUA

Two of the possible changes (UUG, CUA) are completely silent, as the resulting codons still code for leucine. These are known as synonymous codons. Two further changes (AUA and GUA) may well have little effect on the protein since the substituted amino acids (isoleucine and valine respectively) are similar to the original leucine (they are all hydrophobic amino acids). Phenylalanine (UUU or UUC codons) is also hydrophobic but is more likely to cause a significant change in the structure of the protein at that point. The significance of the change to UCA, resulting in the substitution of serine (which is considerably different) for leucine will depend on the role played by that amino acid (and its neighbors) in the overall function or conformation of the protein.

The final two changes (UAA, UGA) are referred to as stop or termination codons (as is a third codon, UAG) since they result in termination of translation; there is normally no tRNA molecule with the corresponding anticodon. The occurrence of such a mutation (also known as a nonsense mutation) will result in the production of a truncated protein; such a protein may or may not be functional, depending on the degree of shortening. The UAG codon was named ‘amber’ which is a literal translation of the German word ‘Bernstein’, the name of one of the investigators who discovered it; subsequently the joke was continued by calling the UAA and UGA codons ‘ochre’ and ‘opal’ respectively, although the latter two names are less commonly used.

A different kind of mutation still involving a change at a single position consists of the deletion or addition of a single nucleotide (or of any number other than a multiple of three). This is known as a frameshift mutation since it results in the reading frame being altered for the remainder of the gene. Since the message is read in triplets, with no punctuation marks (the reading frame being determined solely by the translation start codon), an alteration in the reading frame will result in the synthesis of the totally different protein from that point on. This point is illustrated in Figure.2.

Point mutations

Figure 2. Frameshift mutation and suppression.
(a) Initial (mRNA) sequence and translated product. 
(b) The deletion of a single base alters the subsequent reading frame producing a different amino acid sequence and encountering a stop codon. 
(c) Addition of a base at a different position restores the original reading frame and may suppress the

In fact, protein synthesis is likely to be terminated quite soon after the position of the deletion. For most genes, the two alternative reading frames are blocked by termination codons, which serve to prevent the production of aberrant proteins by mistakes in translation. Non-translated regions also often contain frequent stop codons, so that the existence of a long region of DNA that does not contain a stop codon in one reading frame (i.e. it has an Open Reading Frame or ORF) is used to identify hitherto unknown genes from the DNA sequence.
If point mutation results in premature termination of translation, it may also affect the expression of other genes downstream in the same operon. This effect is known as polarity and needs to be considered in genetic analysis.

Conditional mutants

There are many genes that do not affect resistance to antibiotics bacteriophages, biosynthesis of essential metabolites or utilization of carbon sources. Some of these genes are indispensable and any mutants defective in those activities would die (or fail to grow). Since this includes a wide range of genes that control the essential functions of the cell, such as DNA replication, it is important to be able to use genetic analysis to understand the role of these genes and their products. This can be done by using conditional mutants. This means that the gene functions normally under certain conditions while the defect is only apparent when the conditions are changed. One of the very useful types of conditional mutation confers temperature sensitivity on the relevant function. So, for example, a strain with a temperature-sensitive mutation in a gene needed for DNA replication would be able to grow normally at, say 308C (the permissive temperature) but would be unable to grow at a higher temperature, such as 428C.

Other types of larger-scale alterations are important in the generation of the natural diversity of micro-organisms. When an extraneous piece of DNA is inserted within a gene, it will usually inactivate that gene. The elements known as Insertion Sequences (IS) have a specific ability to insert into other DNA sequences, thus generating insertion mutations. 

Transposons are essentially similar to IS elements in that they have the ability to move (transpose) from one site to another; they differ in carrying one or more identifiable genetic markers. The most widely studied transposons carry antibiotic resistance genes and have played a key role in the evolution and spread of antibiotic resistance.

Instead of moving from one site to another, a region of DNA may flip around into the opposite orientation. If this invertible region contains the signals needed for expression of an adjacent gene, inversion will switch the associated gene on or off in a readily reversible (but still inherited) manner. The best-studied example of this effect is the variation of the flagellar antigens of Salmonella typhimurium. Insertion sequences, transposons, and invertible sequences are covered more fully in the article.

Extrachromosomal agents and horizontal gene transfer

horizontal gene transfer

In addition to alterations of the structure of the chromosomal DNA, variation in bacteria commonly occurs by the acquisition (or loss) of extrachromosomal DNA, either in the form of plasmids or bacteriophages. A wide range of characteristics, notably antibiotic resistance, can be encoded by these extrachromosomal elements. The transfer of genetic information from one strain to another is known as horizontal gene transfer and in some species may affect the structure of the chromosome itself, as well as the acquisition of extrachromosomal elements. Plasmids are considered in more detail in the article and horizontal gene transfer is covered in the article.

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