Mutation

Part of the Biology series on
Genetics
Key components

Chromosome
DNA · RNA
Genome
Heredity
Mutation
Nucleotide
Variation

Index
Outline

History and topics

Introduction
History

Evolution · Molecular
Population genetics
Mendelian inheritance
Quantitative genetics
Molecular genetics

Research

DNA sequencing
Genetic engineering
Genomics · Topics
Medical genetics

Branches in genetics

Biology portal
Part of the Biology series on
Evolution
Mechanisms and processes

Adaptation
Genetic drift
Gene flow
Mutation
Natural selection
Speciation

Research and history

Introduction
Evidence
Evolutionary history of life
History
Level of support
Modern synthesis
Objections / Controversy
Social effect
Theory and fact

Evolutionary biology fields

Cladistics
Ecological genetics
Evolutionary development
Evolutionary psychology
Molecular evolution
Phylogenetics
Population genetics
Systematics

Biology portal ·

Mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. Mutations are caused by radiation, viruses, transposons and mutagenic chemicals, as well as errors that occur during meiosis or DNA replication.[1][2][3] They can also be induced by the organism itself, by cellular processes such as hypermutation.

Mutation can result in several different types of change in DNA sequences; these can either have no effect, alter the product of a gene, or prevent the gene from functioning properly or completely. Studies in the fly Drosophila melanogaster suggest that if a mutation changes a protein produced by a gene, this will probably be harmful, with about 70 percent of these mutations having damaging effects, and the remainder being either neutral or weakly beneficial.[4] Due to the damaging effects that mutations can have on cells, organisms have evolved mechanisms such as DNA repair to remove mutations.[1] Therefore, the optimal mutation rate for a species is a trade-off between costs of a high mutation rate, such as deleterious mutations, and the metabolic costs of maintaining systems to reduce the mutation rate, such as DNA repair enzymes.[5] Viruses that use RNA as their genetic material have rapid mutation rates,[6] which can be an advantage since these viruses will evolve constantly and rapidly, and thus evade the defensive responses of e.g. the human immune system.[7]

Contents

Description

Mutations can involve large sections of DNA becoming duplicated, usually through genetic recombination.[8] These duplications are a major source of raw material for evolving new genes, with tens to hundreds of genes duplicated in animal genomes every million years.[9] Most genes belong to larger families of genes of shared ancestry.[10] Novel genes are produced by several methods, commonly through the duplication and mutation of an ancestral gene, or by recombining parts of different genes to form new combinations with new functions.[11][12] Here, domains act as modules, each with a particular and independent function, that can be mixed together to produce genes encoding new proteins with novel properties.[13] For example, the human eye uses four genes to make structures that sense light: three for color vision and one for night vision; all four arose from a single ancestral gene.[14] Another advantage of duplicating a gene (or even an entire genome) is that this increases redundancy; this allows one gene in the pair to acquire a new function while the other copy performs the original function.[15][16] Other types of mutation occasionally create new genes from previously noncoding DNA.[17][18]

Changes in chromosome number may involve even larger mutations, where segments of the DNA within chromosomes break and then rearrange. For example, two chromosomes in the Homo genus fused to produce human chromosome 2; this fusion did not occur in the lineage of the other apes, and they retain these separate chromosomes.[19] In evolution, the most important role of such chromosomal rearrangements may be to accelerate the divergence of a population into new species by making populations less likely to interbreed, and thereby preserving genetic differences between these populations.[20]

Sequences of DNA that can move about the genome, such as transposons, make up a major fraction of the genetic material of plants and animals, and may have been important in the evolution of genomes.[21] For example, more than a million copies of the Alu sequence are present in the human genome, and these sequences have now been recruited to perform functions such as regulating gene expression.[22] Another effect of these mobile DNA sequences is that when they move within a genome, they can mutate or delete existing genes and thereby produce genetic diversity.[2]

A mutation has caused this garden moss rose to produce flowers of different colors. This is a somatic mutation that may also be passed on in the germ line.

In multicellular organisms with dedicated reproductive cells, mutations can be subdivided into germ line mutations, which can be passed on to descendants through their reproductive cells, and somatic mutations (also called acquired mutations)[23], which involve cells outside the dedicated reproductive group and which are not usually transmitted to descendants. If the organism can reproduce asexually through mechanisms such as cuttings or budding the distinction can become blurred.

For example, plants can sometimes transmit somatic mutations to their descendants asexually or sexually where flower buds develop in somatically mutated parts of plants. A new mutation that was not inherited from either parent is called a de novo mutation. The source of the mutation is unrelated to the consequence, although the consequences are related to which cells were mutated.

Nonlethal mutations accumulate within the gene pool and increase the amount of genetic variation[24]. The abundance of some genetic changes within the gene pool can be reduced by natural selection, while other "more favorable" mutations may accumulate and result in adaptive evolutionary changes.

For example, a butterfly may produce offspring with new mutations. The majority of these mutations will have no effect; but one might change the color of one of the butterfly's offspring, making it harder (or easier) for predators to see. If this color change is advantageous, the chance of this butterfly surviving and producing its own offspring are a little better, and over time the number of butterflies with this mutation may form a larger percentage of the population.

Neutral mutations are defined as mutations whose effects do not influence the fitness of an individual. These can accumulate over time due to genetic drift. It is believed that the overwhelming majority of mutations have no significant effect on an organism's fitness. Also, DNA repair mechanisms are able to mend most changes before they become permanent mutations, and many organisms have mechanisms for eliminating otherwise permanently mutated somatic cells.

Mutation is generally accepted by biologists as the mechanism by which natural selection acts, generating advantageous new traits that survive and multiply in offspring as well as disadvantageous traits, in less fit offspring, that tend to die out.

Causes

Two classes of mutations are spontaneous mutations (molecular decay) and induced mutations caused by mutagens.

Spontaneous mutations on the molecular level can be caused by:

A covalent adduct between benzo[a]pyrene, the major mutagen in tobacco smoke, and DNA[25]

Induced mutations on the molecular level can be caused by:

DNA has so-called hotspots, where mutations occur up to 100 times more frequently than the normal mutation rate. A hotspot can be at an unusual base, e.g., 5-methylcytosine.

Mutation rates also vary across species. Evolutionary biologists have theorized that higher mutation rates are beneficial in some situations, because they allow organisms to evolve and therefore adapt more quickly to their environments. For example, repeated exposure of bacteria to antibiotics, and selection of resistant mutants, can result in the selection of bacteria that have a much higher mutation rate than the original population (mutator strains).

Classification of mutation types

Illustrations of five types of chromosomal mutations.
Selection of disease-causing mutations, in a standard table of the genetic code of amino acids.[29]

By effect on structure

The sequence of a gene can be altered in a number of ways. Gene mutations have varying effects on health depending on where they occur and whether they alter the function of essential proteins. Mutations in the structure of genes can be classified as:

By effect on function

By effect on fitness

In applied genetics it is usual to speak of mutations as either harmful or beneficial.

In theoretical population genetics, it is more usual to speak of such mutations as deleterious or advantageous. In the neutral theory of molecular evolution, genetic drift is the basis for most variation at the molecular level.

In reality, viewing the fitness effects of mutations in these discrete categories is an oversimplification. Attempts have been made to infer the distribution of fitness effects using mutagenesis experiments or theoretical models derived from molecular sequence data. However, the current distribution is still uncertain, and some aspects of the distribution likely vary between species.[33]

By inheritance

By pattern of inheritance The human genome contains two copies of each gene – a paternal and a maternal allele.

By impact on protein sequence

Special classes

Nomenclature

Nomenclature of mutations specify the type of mutation and base or amino acid changes.

Harmful mutations

Changes in DNA caused by mutation can cause errors in protein sequence, creating partially or completely non-functional proteins. To function correctly, each cell depends on thousands of proteins to function in the right places at the right times. When a mutation alters a protein that plays a critical role in the body, a medical condition can result. A condition caused by mutations in one or more genes is called a genetic disorder. Some mutations alter a gene's DNA base sequence but do not change the function of the protein made by the gene. Studies of the fly Drosophila melanogaster suggest that if a mutation does change a protein, this will probably be harmful, with about 70 percent of these mutations having damaging effects, and the remainder being either neutral or weakly beneficial.[35] However, studies in yeast have shown that only 7% of mutations that are not in genes are harmful.[36]

If a mutation is present in a germ cell, it can give rise to offspring that carries the mutation in all of its cells. This is the case in hereditary diseases. On the other hand, a mutation may occur in a somatic cell of an organism. Such mutations will be present in all descendants of this cell within the same organism, and certain mutations can cause the cell to become malignant, and thus cause cancer[37].

Often, gene mutations that could cause a genetic disorder are repaired by the DNA repair system of the cell. Each cell has a number of pathways through which enzymes recognize and repair mistakes in DNA. Because DNA can be damaged or mutated in many ways, the process of DNA repair is an important way in which the body protects itself from disease.

Beneficial mutations

Although most mutations that change protein sequences are neutral or harmful, some mutations have a positive effect on an organism. In this case, the mutation may enable the mutant organism to withstand particular environmental stresses better than wild-type organisms, or reproduce more quickly. In these cases a mutation will tend to become more common in a population through natural selection.

For example, a specific 32 base pair deletion in human CCR5 (CCR5-Δ32) confers HIV resistance to homozygotes and delays AIDS onset in heterozygotes.[38] The CCR5 mutation is more common in those of European descent. One possible explanation of the etiology of the relatively high frequency of CCR5-Δ32 in the European population is that it conferred resistance to the bubonic plague in mid-14th century Europe. People with this mutation were more likely to survive infection; thus its frequency in the population increased.[39] This theory could explain why this mutation is not found in southern Africa, where the bubonic plague never reached. A newer theory suggests that the selective pressure on the CCR5 Delta 32 mutation was caused by smallpox instead of the bubonic plague.[40]

Another example, is Sickle cell disease which is a blood disorder in which the body produces an abnormal type of the oxygen-carrying substance hemoglobin in the red blood cells. One-third of all indigenous inhabitants of Sub-Saharan Africa carry the gene[41], because in areas where malaria is common, there is a survival value in carrying only a single sickle-cell gene (sickle cell trait).[42] Those with only one of the two alleles of the sickle-cell disease are more resistant to malaria, since the infestation of the malaria plasmodium is halted by the sickling of the cells which it infests.

Prion mutation

Prions are proteins and do not contain genetic material. However, prion replication has been shown to be subject to mutation and natural selection just like other forms of replication.[43]

See also

  • Aneuploidy
  • Antioxidant
  • Budgerigar colour genetics
  • Homeobox
  • Macromutation
  • Muller's morphs
  • Mutant
  • Mutagenesis
  • Polyploidy
  • Robertsonian translocation
  • Signature tagged mutagenesis
  • Site-directed mutagenesis
  • TILLING (molecular biology)

References

  1. 1.0 1.1 Bertram J (2000). "The molecular biology of cancer". Mol. Aspects Med. 21 (6): 167–223. doi:10.1016/S0098-2997(00)00007-8. PMID 11173079. 
  2. 2.0 2.1 Aminetzach YT, Macpherson JM, Petrov DA (2005). "Pesticide resistance via transposition-mediated adaptive gene truncation in Drosophila". Science 309 (5735): 764–7. doi:10.1126/science.1112699. PMID 16051794. 
  3. Burrus V, Waldor M (2004). "Shaping bacterial genomes with integrative and conjugative elements". Res. Microbiol. 155 (5): 376–86. doi:10.1016/j.resmic.2004.01.012. PMID 15207870. 
  4. 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. 104 (16): 6504–10. doi:10.1073/pnas.0701572104. PMID 17409186. 
  5. Sniegowski P, Gerrish P, Johnson T, Shaver A (2000). "The evolution of mutation rates: separating causes from consequences". Bioessays 22 (12): 1057–66. doi:10.1002/1521-1878(200012)22:12<1057::AID-BIES3>3.0.CO;2-W. PMID 11084621. 
  6. Drake JW, Holland JJ (1999). "Mutation rates among RNA viruses". Proc. Natl. Acad. Sci. U.S.A. 96 (24): 13910–3. doi:10.1073/pnas.96.24.13910. PMID 10570172. PMC 24164. http://www.pnas.org/content/96/24/13910.long. 
  7. Holland J, Spindler K, Horodyski F, Grabau E, Nichol S, VandePol S (1982). "Rapid evolution of RNA genomes". Science 215 (4540): 1577–85. doi:10.1126/science.7041255. PMID 7041255. 
  8. Hastings, P J; Lupski, JR; Rosenberg, SM; Ira, G (2009). "Mechanisms of change in gene copy number". Nature Reviews. Genetics 10 (8): 551–564. doi:10.1038/nrg2593. PMID 19597530. 
  9. Carroll SB, Grenier J, Weatherbee SD (2005). From DNA to Diversity: Molecular Genetics and the Evolution of Animal Design. Second Edition. Oxford: Blackwell Publishing. ISBN 1-4051-1950-0. 
  10. Harrison P, Gerstein M (2002). "Studying genomes through the aeons: protein families, pseudogenes and proteome evolution". J Mol Biol 318 (5): 1155–74. doi:10.1016/S0022-2836(02)00109-2. PMID 12083509. 
  11. Orengo CA, Thornton JM (2005). "Protein families and their evolution-a structural perspective". Annu. Rev. Biochem. 74: 867–900. doi:10.1146/annurev.biochem.74.082803.133029. PMID 15954844. 
  12. Long M, Betrán E, Thornton K, Wang W (November 2003). "The origin of new genes: glimpses from the young and old". Nat. Rev. Genet. 4 (11): 865–75. doi:10.1038/nrg1204. PMID 14634634. 
  13. Wang M, Caetano-Anollés G (2009). "The evolutionary mechanics of domain organization in proteomes and the rise of modularity in the protein world". Structure 17 (1): 66–78. doi:10.1016/j.str.2008.11.008. PMID 19141283. 
  14. Bowmaker JK (1998). "Evolution of colour vision in vertebrates". Eye (London, England) 12 (Pt 3b): 541–7. PMID 9775215. 
  15. Gregory TR, Hebert PD (1999). "The modulation of DNA content: proximate causes and ultimate consequences". Genome Res. 9 (4): 317–24. doi:10.1101/gr.9.4.317 (inactive 2009-11-14). PMID 10207154. http://genome.cshlp.org/content/9/4/317.full. 
  16. Hurles M (July 2004). "Gene duplication: the genomic trade in spare parts". PLoS Biol. 2 (7): E206. doi:10.1371/journal.pbio.0020206. PMID 15252449. 
  17. Liu N, Okamura K, Tyler DM (2008). "The evolution and functional diversification of animal microRNA genes". Cell Res. 18 (10): 985–96. doi:10.1038/cr.2008.278. PMID 18711447. PMC 2712117. http://www.nature.com/cr/journal/v18/n10/full/cr2008278a.html. 
  18. Siepel A (October 2009). "Darwinian alchemy: Human genes from noncoding DNA". Genome Res. 19 (10): 1693–5. doi:10.1101/gr.098376.109. PMID 19797681. PMC 2765273. http://genome.cshlp.org/content/19/10/1693.full. 
  19. Zhang J, Wang X, Podlaha O (2004). "Testing the chromosomal speciation hypothesis for humans and chimpanzees". Genome Res. 14 (5): 845–51. doi:10.1101/gr.1891104. PMID 15123584. 
  20. Ayala FJ, Coluzzi M (2005). "Chromosome speciation: humans, Drosophila, and mosquitoes". Proc. Natl. Acad. Sci. U.S.A. 102 (Suppl 1): 6535–42. doi:10.1073/pnas.0501847102. PMID 15851677. PMC 1131864. http://www.pnas.org/content/102/suppl.1/6535.full. 
  21. Hurst GD, Werren JH (2001). "The role of selfish genetic elements in eukaryotic evolution". Nat. Rev. Genet. 2 (8): 597–606. doi:10.1038/35084545. PMID 11483984. 
  22. Häsler J, Strub K (2006). "Alu elements as regulators of gene expression". Nucleic Acids Res. 34 (19): 5491–7. doi:10.1093/nar/gkl706. PMID 17020921. 
  23. "Genome Dictionary". http://www.theodora.com/genetics/#somaticcellgeneticmutation. Retrieved 2010-06-06. .
  24. doi:10.1038/nrg2146
    This citation will be automatically completed in the next few minutes. You can jump the queue or expand by hand
  25. Created from PDB 1JDG
  26. Pfohl-Leszkowicz A, Manderville RA (January 2007). "Ochratoxin A: An overview on toxicity and carcinogenicity in animals and humans". Mol Nutr Food Res 51 (1): 61–99. doi:10.1002/mnfr.200600137. PMID 17195275. 
  27. Kozmin S, Slezak G, Reynaud-Angelin A, Elie C, de Rycke Y, Boiteux S, Sage E (September 2005). "UVA radiation is highly mutagenic in cells that are unable to repair 7,8-dihydro-8-oxoguanine in Saccharomyces cerevisiae". Proc. Natl. Acad. Sci. U.S.A. 102 (38): 13538–43. doi:10.1073/pnas.0504497102. PMID 16157879. PMC 1224634. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=16157879. 
  28. 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. PMID 3023954. PMC 367868. http://mcb.asm.org/cgi/pmidlookup?view=long&pmid=3023954. 
  29. References for the image are found in Wikimedia Commons page at: Commons:File:Notable mutations.svg#References.
  30. Freese, Ernst (April 1959). "The Difference between Spontaneous and Base-Analogue Induced Mutations of Phage T4". Proc. Natl. Acad. Sci. U.S.A. 45 (4): 622–33. doi:10.1073/pnas.45.4.622. PMID 16590424. 
  31. Freese, Ernst (1959). "The Specific Mutagenic Effect of Base Analogues on Phage T4". J. Mol. Biol. 1: 87–105. doi:10.1016/S0022-2836(59)80038-3. 
  32. Ellis NA, Ciocci S, German J (2001). "Back mutation can produce phenotype reversion in Bloom syndrome somatic cells". Hum Genet 108 (2): 167–73. doi:10.1007/s004390000447. PMID 11281456. http://link.springer.de/link/service/journals/00439/bibs/1108002/11080167.htm. 
  33. Eyre-Walker A, Keightley PD (August 2007). "The distribution of fitness effects of new mutations". Nature 8 (8): 610-8. PMID 17637733. http://www.lifesci.sussex.ac.uk/home/Adam_Eyre-Walker/Website/Publications_files/EWNRG07.pdf. 
  34. Medterms.com
  35. 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. 104 (16): 6504–10. doi:10.1073/pnas.0701572104. PMID 17409186. 
  36. Doniger SW, Kim HS, Swain D, et al. (August 2008). "A catalog of neutral and deleterious polymorphism in yeast". PLoS Genet. 4 (8): e1000183. doi:10.1371/journal.pgen.1000183. PMID 18769710. 
  37. Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M (1993). "Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis". Nature 363 (6429): 558–61. doi:10.1038/363558a0. PMID 8505985. 
  38. Sullivan, Amy D. et al. (2001). "The coreceptor mutation CCR5Δ32 influences the dynamics of HIV epidemics and is selected for by HIV". PNAS 95 (18): 10214–10219. doi:10.1073/pnas.181325198. PMID 11517319. PMC 56941. http://www.pnas.org/content/98/18/10214.full. 
  39. "PBS:Secrets of the Dead. Case File: Mystery of the Black Death". http://www.pbs.org/wnet/secrets/previous_seasons/case_plague/clues.html. 
  40. Galvani A, Slatkin M (2003). "Evaluating plague and smallpox as historical selective pressures for the CCR5-Δ32 HIV-resistance allele". Proc Natl Acad Sci USA 100 (25): 15276–9. doi:10.1073/pnas.2435085100. PMID 14645720. 
  41. Sicklecell.md
  42. Sicklecell.md FAQ: "Why is Sickle Cell Anaemia only found in Black people?
  43. 'Lifeless' prion proteins are 'capable of evolution'

External links