Mutation

A mutation is a change in a gene (or genetic material) that is heritable and results in a mutant (as opposed to the Wild - type)^[1]. A mutation produces mutant mRNA, which is translated into a mutant protein. As such, they can be exhibited as a mutation in the organism as long as the mutation is not a silent mutation. Mutations can alter the protein produced, affect the function of the gene, or have no effect at all as in silent mutation. Studies show that around 70% of mutations^[2] will have damaging effects to the organism, with the others being either beneficial or silent. While a mutation is typically damaging, some can have positive effects on the organism and aid in Evolution.

Mutation is the change in DNA sequence of a cell due to errors in DNA replication or during meiosis. It can also be caused by environmental agents called mutagens though induced mutation. Mutagens are physical or chemical agents that lead to changes in the genetic material of an organism. There are various types of mutations:

Point mutation is the addition or deletion of a single base pair within the DNA. It usually occurs through base substitution and even though it only causes a minute change in DNA it can still have important consequences. Silent mutation is the change in nucleotide sequence of an amino acid in a polypeptide. Even though an nucleotide sequence is changed, it does not alter the amino acid of the polypeptide, this is because silent mutation only occurs in the third base of codons as genetic code is degenerate. As silent mutations do not affect the function of the protein, it is considered as a neutral mutation.

Missense mutation occurs through base substitution which changes a single amino acid in the polypeptide. Missense mutation can also be considered as a neutral mutation as it may not alter the function of the protein. They are not always neutral mutation and can also have a large effect on the function of the protein.

Nonsense mutation is another mutation which can have a dramatic effect on the polypeptides sequence. It affects the codons of the polypeptide, changing a normal codon to a stop codon. This causes early termination of translation resulting in a truncated polypeptide, which is less likely to function properly.

Frameshift mutation can also have a dramatic effect on the polypeptide sequence even causing inhibition of protein function. It involves the addition or deletion of nucleotides which are not in multiples of three. As codons come in multiples of three, frameshift causes a completely different amino acid sequence to be read downstream from the point of mutation^[3].

Contents 1 Causes 2 Types 3 Effects 4 References

Causes

Mutations can be either spontaneous or induced. They often occur at hotspots, where they are more likely to happen. The rate at which this and other mutations happen vary by species, and can have both damaging and beneficial effects.

Spontaneous mutations occur on a molecular level and include;

• Tautomerism - A hydrogen atom or bond is repositioned to bring about incorrect base pairings^[4].
• Deamination - Removal of an amine group.
• Depurination - A purine base (A or G) is lost^[5].
• Slipped strand mispairing - Template strand joined in the wrong spot^[6].

Induced mutations on a molecular level include;

• Hydroxylamine - NH₂OH^[7]
• Base analogs - substitute for a regular base^[8].
• Alkylating agents - mutates all types of DNA.
• Oxidative damage - involved in many diseases^[9].
• Nitrous acid - Amine groups to Diazo groups.
• Radiation - both Ultraviolet and Ionising.
• Viral infections - such as herpes simplex^[10].

Types

Point mutations exchange one Nucleotide for another. Transitions see a purine changed for a purine, or a pyrimidine for a pyrimidine, while transversion sees a purine for a pyrimidine or vice versa. The former is the most common.

• Silent mutations code for the same amino acid due to the degenerate code, so the same protein is produced.
• Missense mutations code for a different amino acid, so a different protein will be produced.
• Nonsense mutations code for a stop codon and result in a truncated protein (ended early).

Insertion mutations occur when a nucleotide is added into the sequence. This will cause a frame shift as all following bases will be read in the wrong frame (different three read). It is more harmful the earlier it is.

Deletion mutations occur when a nucleotide is removed from the sequence. This also causes a frameshift as all following bases are moved back one. It is also more harmful the earlier it is found.

Effects

Mutations can be classed as loss of function or gain of function. Depending on the protein affected by the mutated sequence, it may result in a complete loss of function in that gene or allow it to gain a new or abnormal function. Loss of function mutations normally exhibit a recessive phenotype, and gain of function usually exhibit a dominant phenotype. Furthermore, all mutations can be either harmful or beneficial, depending on whether they increase the fitness of the organism and make it more suited for survival. This is because mutations drive natural selection, and thus also for evolution to occur.

Harmful mutations is where the Fitness of the organism is decreased and so its Survival becomes less likely. Resultant genetic disorders can be hereditary if present in germ cells, and while this is useful for natural selection in beneficial mutations, it is not useful in harmful mutations. Most mutations associated with genetic disorders are classed as harmful.

Beneficial mutations is where the fitness of the organism is increased and so its survival becomes more likely. Environmental changes mean that organisms with specific mutations are better adapted to survive, and so are more likely to reproduce and pass on this mutation to their offspring. This drives evolution as eventually, these mutations could give rise to a new Species.Both types of mutations can be seen in Sickle Cell disease. The sickle-shape of the red blood cells is harmful to those who carry both Recessive alleles and therefore suffer from the disorder. However, having just one of the alleles and thus being a carrier still causes some sickle cell symptoms, but also gives the benefit of Malaria resistance. This is because malaria infection is stopped when a blood cell sickles^[11]. In Africa, there is a selection pressure against malaria, so carriers of the sickle cell allele are more likely to reproduce and pass on this resistance.

References

1. ↑ Hartl DL, Jones EW (2009). "Genetics; analysis of genes and genomes". Jones and Bartlett Publishers. 7th Edition. 26-27.
2. ↑ Sawyer SA, Parsch J, Zhang Z, Hartl DL (2007). "Prevalence of positive selection among nearly neutral amino acid replacements in Drosophila". Proc. Natl. Acad. Sci. U.S.A, 6504–10.
3. ↑ Robert J. Brooker, Eric P. Widmaier, Linda E. Graham, Peter D. Stilling. (2008) Biology, McGraw-Hill International Edition, New York: McGraw-Hill. Chapter 14, Page 278-283.
4. ↑ Roman M. Balabin (2009). "Tautomeric equilibrium and hydrogen shifts in tetrazole and triazoles: Focal-point analysis and ab initio limit". J. Chem. Phys. 131
5. ↑ Lindahl, T. (22 April 1993). "Instability and decay of the primary structure of DNA". Nature 362 (6422): 709–715
6. ↑ Levinson G, Gutman, G. A. (1987). "Slipped-Strand Mispairing: A Major Mechanism for DNA Sequence Evolution". Mol. Biol. Evol. 4 (3): 203–221
7. ↑ Inoue S, Kawanishi S, Yamamoto K (1993). "Site-specific DNA damage and 8-hydroxydeoxyguanosine formation by hydroxylamine and 4-hydroxyaminoquinoline 1-oxide." Carcinogenesis. Jul;14(7):1397-401.
8. ↑ Griffiths AJ, Wessler SR, Lewontin RC, Gelbart WM, Suzuki DT, Miller JH. Introduction to Genetic Analysis, 8th ed. New York:W.H.Freeman and Co, 2005.
9. ↑ Sies, H. (1985). "Oxidative stress: introductory remarks". In H. Sies, (Ed.). Oxidative Stress. London: Academic Press. pp. 1–7.
10. ↑ Pilon L, Langelier Y, Royal A (1 August 1986). "Herpes simplex virus type 2 mutagenesis: characterization of mutants induced at the hprt locus of nonpermissive XC cells". Mol. Cell. Biol. 6 (8): 2977–83
11. ↑ Aidoo M, Kariuki S, Kolczak MS, Kuile FOT, Lal AA, McElroy PD, Nahlen BL, Terlouw DJ, Udhayakumar V (2002). "Protective effects of the sickle cell gene against malaria morbidity and mortality." The Lancet. 359; 1311-1312.