Point Mutations

9 Key excerpts on "Point Mutations"

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  Sequence Alignment

  Methods, Models, Concepts, and Strategies

  • Michael S. Rosenberg, Michael S. Rosenberg Ph. D.(Authors)
  • 2009(Publication Date)
  • University of California Press

    (Publisher)

  In rare cases, a mutation may be advantageous and as a result may propagate throughout the population (Alberts et al. 1994 ). Point Mutations Point Mutations occur when one nucleotide is exchanged for another. When these mutations occur within coding regions of DNA, they can be classified as one of three types: silent , nonsense , or missense (Weaver and Hedrick 1992 ). Molecular Mechanisms of Indels 27 Silent Mutations When a silent mutation occurs, the codon is altered such that it results in the translation of the same amino acid. Therefore, no effect is seen at the protein sequence level and such mutations can be seen as neutral. Nonsense Mutations A nonsense mutation occurs when the base change results in the production of a stop codon. This leads to the translation of truncated proteins and is often deleterious. However, a nonsense mutation toward the beginning of the sequence will have a potentially more dramatic effect than one that occurs near the end of the sequence. Missense Mutations In this case, the codon is altered such that it results in the translation of a different amino acid. These mutations can be deleterious, effectively neutral if they lead to no change in biological activity, or, in rare cases, advantageous. Point accepted missense mutations are accounted for in protein sequence alignments by using mutation matrices. These matrices are essentially tables of scores that weigh changes in amino acids according to the differences in their physical, chemical, or structural properties. Certain mutations that appear to be Point Mutations could be con-sidered to have occurred through the deletion of one amino acid fol-lowed by the replacement of another. Intuitively, it would seem that these events will be far less likely than a true point mutation. True indel events have a greater effect on the gene products and can sig-nificantly alter the amino acid sequences.

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  Point Mutation

  • Colin Logie(Author)
  • 2012(Publication Date)
  • IntechOpen

    (Publisher)

  Part 1 Current Views on Point Mutation Theory 1 Point Mutations, Their Transition Rates and Involvements in Human and Animal Disorders Viliam Šnábel Parasitological Institute, Slovak Academy of Sciences, Košice, Slovakia 1. Introduction Point mutation or single base substitution is the replacement of a single base nucleotide with another nucleotide of the genetic material. Point Mutations can be divided into transitions, changes between the purines A and G, or changes between the pyrimidines C and T, and transversions, changes between purines and pyrimidines. A fundamental aspect of DNA point mutation is the observation that transitional nucleotide changes commonly occur with greater frequency than transversional changes. This bias is primarily due to the biochemical structure of the nucleotide bases and the similar chemical properties of complementary base pairing (Topal & Fresco, 1976). Estimates of the bias are important for understanding the mechanisms of nucleotide substitution, assessing mode and strength of natural selection, and the relative abundance of transitional and/or transversional mutations has important consequences in epidemiological research as each class is associated with different diseases (Wakeley, 1996; Martínez-Arias et al., 2001). This review addresses the issue to which extent transition bias is ubiquitous among living organisms and whether this is similar in different species, along with the screening of Point Mutations associated with diseases and disorders. 2. Point Mutations and transitional bias Within coding sequences, transitional changes are often synonymous whereas transversional changes are not. When both types of changes lead to a change in protein sequence, the transitional change is often less severe with respect to the chemical properties of the original and mutant amino acids (Zhang, 2000).

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  Population Genetics

  • Matthew B. Hamilton(Author)
  • 2021(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  The following sections will present classical population genetic models for the fate of a new mutation, the impact of mutation on allele fre- quencies in a population, and the predicted balance between the removal of genetic variation by genetic drift and its replacement by mutation. This chapter will also cover several models of the way new alleles are introduced by mutation commonly employed in population genetics, illustrated with applications that highlight the consequences of these models. The final section of the chapter will show how the process of mutation can be incorporated into genea- logical branching models. Mutation is a broad term that encompasses a wide variety of events that lead to alterations in DNA sequences. Point Mutations lead to the replace- ment of a single base pair by another nucleotide. Point Mutations to chemically similar nucleotides (purine to purine (A G) or pyrimidine to pyrimidine (C T)) are called transitions, while point muta- tions to chemically dissimilar nucleotides (purine to pyrimidine or pyrimidine to purine) are called transversions. Base substitutions that occur within coding genes may or may not alter the protein pro- duced by that gene. Synonymous or silent muta- tions result in the same translation of a DNA sequence into a protein due to the redundant nature of the genetic code, while nonsynonymous or mis- sense mutations result in a codon that does change the resulting amino acid sequence. Mutation can take the form of insertion or dele- tion of DNA sequences, often referred to by the short-hand indels. Indels within coding regions result in frameshift mutations if the change in sequence length is not an even multiple of three, altering the translation of a DNA sequence and possibly creating premature stop codons. Indels may range in size from a single base pair to segments of chromosomes containing many thousands of base Population Genetics, Second Edition.

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  Advanced Molecular Biology

  A Concise Reference

  • Richard Twyman(Author)
  • 2018(Publication Date)
  • Garland Science

    (Publisher)

  Chapter 15

  Mutation and Selection

  Fundamental concepts and definitions

  • A mutation is a stable, heritable change in genotype caused by an alteration to the nucleotide sequence in a particular region of the genome (c.f. epimutation, paramatation). A gene, genome, cell or individual carrying a given mutation is a mutant.
  • Mutations can be localized (i.e. affecting a single nucleotide or a small cluster of nucleotides) or can involve large segments of the genome. In the former category, gene mutations occur within a gene and can affect the nature of the gene product or interfere with its expression, whereas extragenic mutations usually have no effect (unless they disrupt a regulatory element). Large-scale mutations involve tens to many thousands of nucleotides and affect whole genes or groups of genes. In eukaryotes, the largest mutations are visible at the cytogenetic level and are termed chromosome mutations (see Chromosome Mutation).
  • Gene mutations convert one allelic form of a gene into another. For many gene loci, there is a wild-type allele which predominates in the population because it confers the greatest fitness (ability to survive and reproduce). This generally encodes the normal, functional product associated with the gene, and the wild-type phenotype reflects this normal gene activity. Other, rare alleles are designated mutant alleles, and the quantity and/or structural properties of the encoded product may differ, generating distinct mutant phenotypes. Gene mutations away from the wild type are usually deleterious or selectively neutral; few are beneficial.
  • Instead of a single wild-type allele, several alleles conferring equal fitness may exist in equilibrium within the population, and the locus is described as polymorphic.

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  Animal Genetics for Chemists

  • Ralph G Wilkins(Author)
  • 2017(Publication Date)
  • Royal Society of Chemistry

    (Publisher)

  Chapter 5 ), in which case there will have been no history of the disease in the family. Alternatively, it may be inherited from an affected parent.

  4.2 TYPES OF MUTATION

  There is a wide range of types of alterations in DNA that lead to a mutation. Slight changes, involving only one or a few nucleotides, can only be detected by full sequencing techniques. On the other hand, whole chunks of DNA, involving millions of base pairs and even entire genes, may be lost or moved around within a chromosome or between chromosomes. These may be detected using karyotype patterns or by spectroscopic techniques (see FISH and SKY in Section 1.4.3 in Chapter 1 ).

  4.3 SMALL CHANGES IN DNA

  4.3.1 Single Nucleotide Polymorphism

  A single nucleotide variation or point mutation in either the coding or non-coding region of the gene (single nucleotide polymorphism, SNP, pronounced “snips”) is the most abundant type of genetic variation in the human genome and accounts for 90% of the differences between individuals. SNPs occur about one in every 300 nucleotides in the human genome. There are a variety of SNPs, most of which are harmless. Those within the intron regions (see Section 3.1 in Chapter 3 ) are termed intronic (iSNP) and those located between genes, i.e. , the intergenic (gSNP) regions, are much more plentiful than the more harmful ones that are within the coding (cSNP) and regulatory (rSNP) regions. About 70% of SNPs involve a nucleotide replacement of C by T. For the altered sequences to be considered a significant SNP, they must occur in over 1% in at least one population. SNPs change little through generations.

  • The single nucleotide change in, for example, GGC to GGA will not lead to a change in the encoded protein since both codons lead to one particular amino acid, namely glycine (Figure 3.6

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  Molecular Biology

  • David P. Clark(Author)
  • 2009(Publication Date)
  • Academic Cell

    (Publisher)

  inherited disease . In fact, all humans are mutants many times over, with a substantial number of errors in their genes. However, there are many different types of mutation and most have only minor effects; in fact, many appear to cause no noticeable defect at all. Relatively few mutations cause such large changes that they attract attention. Moreover, higher organisms have two copies of each gene. This means that if one copy is damagedby mutation, there is a back-up copy which can be used to produce the correct protein. This often suppresses the potential defect, unless the mutation is dominant. It has been estimated that a typical human carries enough harmful mutations to total approximately eight lethal equivalents per genome. Put another way, if humans were haploid, with only a single copy of each gene, the average person would be dead eight times over. Due to mutations accumulated over the centuries, all humans are genetically different from their ancestors.

  Most mutations cause little observable harm. A few unusually severe mutations are responsible for inherited disease.

  inherited disease	Disease due to a genetic defect that is passed on from one generation to the next
  mutation	An alteration in the DNA (or RNA) that comprises the genetic information

  The Major Types of Mutation

  A single mutation is a single event and a multiple mutation is the result of several events. A single mutational event, however large or complex its effect, is regarded as a single mutation. A mutation that involves only a single base is known as a point mutation . A null mutation totally inactivates a gene; the expression “null mutation” is a genotypic term. Complete absence of a gene product may or may not cause a detectable phenotype. A tight mutation is one whose phenotype is clear-cut. The complete loss of a particular enzyme may result in no product in a particular biochemical pathway. For example, the complete inability of a bacterium to grow if provided with a certain sugar is an example of a tight mutation. A leaky mutation is one where partial activity remains. For example, 10 percent residual enzyme activity might allow a bacterium to still grow, albeit very slowly.

  Many different types of mutation occur. Some affect a single base, others affect large segments of DNA.

  The sequence of a DNA molecule may be altered in many different ways. Such mutations have a variety of outcomes that depend in part on the nature of the change and in part on the role of the DNA sequence that was altered. The major types of sequence alteration are as follows, and will be discussed separately below:

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  The Human Genome

  A User's Guide

  • Julia E. Richards, R. Scott Hawley(Authors)
  • 2004(Publication Date)
  • Academic Press

    (Publisher)

  So for myocilin, does less severe glaucoma result from a nonsense mutation because it is operating through a different loss-of-function mechanism instead of acting as a monkey wrench? That re-mains to be seen, and some studies suggest that the difference may not be anything quite that simple. MUTATIONS DON’T ALWAYS CHANGE THE PROTEIN Notice that Point Mutations are not always missense mutations or nonsense mutations—that is, sometimes you can change a single base within the coding sequence and get no change in the amino acid or the protein. Why? Remem-ber that there are sixty-four different codons that designate which amino acid will be used, and there are only twenty amino acids. This means that there is redundancy in the code. So some changes in the DNA sequence will replace one of the codons specifying leucine with a different codon specifying leucine. We joke sometimes about finding a leucine-to-leucine mutation, meaning a change in the sequence that does not affect the protein. These are called silent mutations (Figure 16.4). Even when a missense mutation does change the protein sequence, some-times this results in no functional change and no change in phenotype. This is especially easy to understand in cases in which an amino acid of very similar size, shape, charge, and polarity replaces the original amino acid. So missense mutations often cause functional problems, but just knowing that there is a change in amino acid is not enough to tell you that this change is neces-sarily bad enough to affect the phenotype. In one disease gene with more than fifty known missense mutations, only about half of them seem to cause the disease. The other half appear to be what we call benign polymorphisms . CHAPTER 16: We Are All Mutants 159 “SILENT” MUTATIONS THAT CAN HAVE AN EFFECT! Most molecular biologists will glance at a newly discovered silent mutation in scorn or disappointment and set it aside as not being a causative mutation.

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  Molecular Evolution and Population Genetics for Marine Biologists

  • Yuri Kartavtsev(Author)
  • 2015(Publication Date)
  • CRC Press

    (Publisher)

  6 GENES, MUTATIONS AND EVOLUTION MAIN GOALS 6.1 Introduction to the Study of Mutation 6.2 Structure and Functions of Genes 6.3 Types of Mutations on DNA Level 6.4 Mutations and Amino Acid Substitutions 6.5 Mutation Rate 6.6 TRAINING COURSE, #6 SUMMARY 1. Mutations lead to the alteration of a current phenotype or to creation of variability, and by this provide a subject for genetic research. Due to this, their importance for genetics and evolution of life in general is obvious. 2. In terms of their function, genes can be classi fi ed into two groups: protein-coding or structural genes and RNA-coding or regulatory genes . Structural genes may participate in regulation too, and in this have no principal difference from the second group of genes. 3. Nucleotide substitutions can be divided into two different classes: transition and transvertion . Transition is the substitution of a purine for another purine (A G) or the substitution of a pyrimidine for another pyrimidine (T C). Transvertions are inverse types of nucleotide substitutions, when a purine is substituted by a pyrimidine and vice versa (G T, A C, C G or A T). 4. Classical geneticists have determined that the rate of mutations, that alter phenotypic characters or induce lethal effects, is of the order of 10 –5 per locus per generation in eukaryotes such as man, Drosophila and corn. The mean rate of amino acid substitution for an average polypeptide is estimated to be 70 Molecular Evolution and Population Genetics for Marine Biologists 4 × 10 –7 per locus per year. Due to the evidences that electrophoresis detects only about one-quarter of all amino acid changes, the rate of amino acid substitutions detectable by electrophoresis is estimated to be about 10 –7 per locus per year. 5. Mutations play the principal role in molecular clocks .

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  Evolutionary Models and Studies in Human Diversity

  • Robert J. Meier, Charlotte M. Otten, Fathi Abdel-Hameed, Robert J. Meier, Charlotte M. Otten, Fathi Abdel-Hameed(Authors)
  • 2011(Publication Date)
  • De Gruyter Mouton

    (Publisher)

  NUCLEOTIDE SUBSTITUTION The most basic point mutation is an alteration in a sequence of nucleo-tides. This usually occurs through the substitution of one nucleotide for another, but it may also be caused by an insertion, duplication, or deletion. In the context of protein evolution, however, the primary emphasis is placed on changes in amino acid sequences. When poly-morphisms in natural populations are discussed, the allelomorphs in question are distinguished by electrostatic charge. This, however, may distinguish only half of the different amino acid substitutions possible (Lewontin and Hubby 1966). Unfortunately, the lack of electrostatic difference does not necessarily imply a lack of adaptive difference, and for this reason some questions remain concerning the validity of conclu-sions based on this type of investigation. We should, nevertheless, be concerned with the question of how many different proteins there are for every electrostatic enzyme variant observed; and for any protein whose amino acid sequence is known, how many different nucleotide sequences (true alleles?) are present in a population for the locus in question. In particular, we are concerned with where and to what degree we should begin to note adaptive character in the variously observed differences. Serine (see the codon catalogue, Figure 6), for example, has six alterna-tive DNA codings. In four of these, UCU, UCC, UCA, and UCG, the identity of the third nucleotide is spurious, at least with respect to coding for serine. The degeneracy of the DNA code is not generally thought to be an accident, and a number of functions have been postulated (Gold-berg and Wittes 1966; Mitchell 1968). However, at this time not enough evidence exists to make a definite conclusion concerning the adaptive character of synonymous codons.

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