Neutral Mutations

11 Key excerpts on "Neutral Mutations"

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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)

  Allowances can be made for more intense periods of selec-tion. This was, however, before molecular biology had fully exposed the massive variation existing at the molecular level. Recently Shaw (1970) estimated that all loci on a genome have undergone substitution. We do not agree that the rates of substitution are constant for all proteins. This would assume that in any protein the number of neutral sites has also remained constant. This reasoning does not allow for functionally related changes that might alter this number. However, for those sites that have retained complete tolerance to mutation throughout the history of the protein, the rates of substitution should be constant. The same situation should exist in DNA that has become functionless. This presents the possibility of a precise method of determining the date of divergence of species or other larger groups of organisms when geo-logical evidence is sparse or inconclusive. The significance of Neutral Mutations in evolution is small when com-pared to the driving force of natural selection. However, neutral muta-tions and stochastic processes may prove to be of some value to the evolving organism; that is, they allow for the absorption of mutations without any burden to the organism. As Kimura and Ohta (1971a) suggested, they may allow for the easy accumulation of intermediate mutations needed to achieve a truly adaptive sequence of amino acids. As Edwards (1972) has stated, Neutral Mutations may be of neutral value only in the sense that a lottery ticket can be said to be valueless because it is likely to be valueless. Because they cost nothing in terms of genetic load, Neutral Mutations might be compared to free lottery tickets. REFERENCES ARNHEIM, N., C. E. TAYLOR 1969 Non-Darwinian evolution: consequences for neutral allelic variation. Nature 223:900-903. AY ALA, F. J. 1972 Darwinian versus non-Darwinian evolution in natural populations of

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  Advanced Molecular Biology

  A Concise Reference

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

    (Publisher)

  Such mutations are described as being selectively neutral because they do not influence the Darwinian fitness of the individual; they include most extragenic mutations. Most mutations which have a phenotypic consequence fall within genes or the regulatory elements which control them. There are three different target sequences for such mutations: the coding region of the gene, noncoding sequences within the transcription unit, and regulatory sequences outside the transcription unit. Many point mutations within genes are neutral because they do not alter either the structure or expression of the encoded product (see Table 15.2). Point mutations which do modify the gene product or its expression in some way are usually deleterious or neutral — a few may be beneficial, but this depends on the selective constraints on the structure of the polypeptide and the environment in which the polypeptide functions (q.v. natural selection, molecular clock). Macromutations occurring within genes or involving genes are generally deleterious because they cause large-scale disruptions (see Table 15.3). The consequences of many different types of mutation are exemplified by the study of hemoglobin disorders (Box 15.1). Whatever the consequences of a mutation per se, whether these effects are expressed at the level of the phenotype depends on several additional factors. (1) Dominance. In diploids, the mutant allele may be recessive to the wild-type allele and its effects will not manifest in the heterozygote. (2) Genetic background and environment. The mutant allele may not be penetrant even in the homozygous state if its. effects can be compensated by nonallelic interactions (e.g. redundant genes, external suppressor mutations) or by environmental factors (e.g

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  DNA Fingerprinting

  • M. Krawczak, J. Schmidtke(Authors)
  • 2020(Publication Date)
  • Taylor & Francis

    (Publisher)

  The principal difference between these two theories is the inevitable adoption of different evolutionary time scales. Since selection acts on individuals, its unit must be generation number. Neo-Darwinian theory would therefore predict that species with short generation times evolve faster than others. In neutral theory, however, mutational pressure plays the predominant role. As we shall see later in this chapter, many mutational mechanisms are concerned with errors in DNA replication and repair. The impact of these processes is determined by the number of divisions that a germ cell undergoes, and is thus clearly dependent on time. Neutral theory would thus predict equal rates of molecular evolution even in species with different generation times, provided their mechanisms of germ cell development exhibit similar physiological properties.

  Since, in terms of evolution, lack of function is equivalent to lack of selection, functionless DNA should evolve more freely than functional parts of the genome and therefore change much faster. However, selectionists would maintain that functionless DNA is not necessarily neutral, because selection operates on whole chromosomal regions. If a nonfunctional mutation arises, just by chance, in close proximity to an advantageous allele of an important gene, its descendants will share the selective advantage of that allele until recombination moves a minority of them on to chromosomes with different genetic backgrounds (haplotypes).

  Nevertheless, the level of sequence diversity observed in non-functional DNA is usually much higher than that seen in regions of functional importance, and techniques for DNA fingerprinting and profiling rely heavily upon this. For example, in the mammalian β-globin genes, exon sequences are more similiar to one another than are some noncoding DNA homologs in humans. Further, even within exons of the same gene, nucleotides at which a mutation does not alter the identity of the amino acid are polymorphic more often than others. These molecular genetic findings strongly support the neutral theory of evolution.

  Promoters of neutral theory also claim that evolution at the phenotype level, and thus in functionally important regions of the genome, has resulted mainly from random processes 1

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  Encyclopedia of Caves

  • William B. White, David C. Culver(Authors)
  • 2011(Publication Date)
  • Academic Press

    (Publisher)

  Neutral Mutations

  Horst Wilkens

  Zoologisches Institut und Zoologisches Museum, University of Hamburg

  Selection dominates all modern interpretations of evolutionary processes and is part of their most efficient explanation. However, this is in contrast with the characteristics at the molecular level of evolution in which random mutations and drift play the major role, whereas external selection only gets involved secondarily, at the phenotypic level. Biologically functionless traits in cave animals are providing some of the rare examples of these basic evolutionary principles manifesting in phenotypic evolution. This is proven by the variability developed by such traits, in particular, during the initial phase of reduction due to deleterious mutations no longer being selected against, which would be necessary to preserve functional capability. The neutral mutation theory states that over the course of time the random accumulation of deleterious mutations leads to the complete reduction of biologically functionless traits such as eyes, pigmentation, or optically triggered behaviour.

  Keywords

  Astyanax; eye regression; Neutral Mutations

  The paradigm of selection dominates all modern interpretations of evolutionary processes and provides their most efficient explanation. However, this is in contrast with the conditions characteristic of the basal process of molecular evolution. Here mutation pressure and drift play the major role (Kimura, 1983 ), whereas as a rule selection only gets involved secondarily, at the phenotypic level. The question is whether these basic principles of molecular evolution, random mutations, and drift may also manifest in phenotypic evolution and can, in some cases, be traced here.

  The reduction and rudimentation of structures is very common throughout nature. It can be observed in wingless birds and insects such as ostriches and carabid beetles. Also baleen whales, which have not only reduced their hind legs but also the teeth, provide spectacular examples. The most conspicuous and curious phenotypes are found in cave-dwelling animals. Eye loss and paleness of the so-called troglobites have stimulated the thinking of scientists from the beginning of research. Even Darwin was aware of the bizarre phenotypic appearance of cave animals, which seemed to him “wrecks of ancient life.” Cave animals are a central object for the study of the causes of regressive evolutionary processes, because most reduced traits may be no longer influenced by persisting biological functions.

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  The Evolution of Biological Information

  How Evolution Creates Complexity, from Viruses to Brains

  • Christoph Adami(Author)
  • 2024(Publication Date)
  • Princeton University Press

    (Publisher)

  Neutral Mutations can have other uses still: some argue that “neutral walks” in fitness landscapes are essential for moving populations to different (unexplored) areas in genetic space where adaptive mutations might be more prevalent (see, e.g., Gavrilets 2004). Besides leading populations to the “foothills” where selection can drive them “uphill,” Neutral Mutations have more subtle uses. In the following, we will explore how populations might adapt to very stressful evolutionary condi- tions. The stress we discuss here is not the usual stress that an organism might be subject to (such as the stress of bacterial infection for a eukaryotic cell, or the stress of viral infection for a bacterial cell). Instead, they are stresses that jeopardize the evolutionary survival of the population. Two such stresses are usually recognized: the threat of high mutation rates and the scepter of small population sizes. We will discuss each one by one, and study how organisms have adapted to deal with them. The lesson we will learn is an important one: evolution is a process that takes place in a complex and changing environment. To survive, a population should adapt to the environment, but it must also adapt to the process itself, making evolution work better for the population under dire circumstances. This is the evolution of robustness. 6.2 Evolution of Mutational Robustness Mutations are essential to the evolutionary process. As we saw in the very first chapter, without mutations, the evolution of novel structures and functions 2. In a curious twist of history, King and Jukes made essentially the same argument inde- pendently a year later (King and Jukes 1969). 326 chapter 6 cannot proceed. But, as with most things, too much of a good thing quickly turns into a nightmare.

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  Bioinformatics and Molecular Evolution

  • Paul G. Higgs, Teresa K. Attwood(Authors)
  • 2013(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  selective sweep. When the advantageous mutation goes to fixation, it may cause other mutations at closely linked points in the sequence to hitch-hike to fixation at the same time. The other mutations may be neutral or even slightly disadvantageous. If they are close to the original mutation, so that there is no recombination between them during the time in which the selective sweep is occuring, then they will be dragged along with the advantageous mutation.

  In recent years, the argument for and against neutral evolution has died down, even if it has not been fully resolved. Neutral Mutations are seen as part of a spectrum of possibilities, and the neutral theory has an established role as a null model. Even if the neutral hypothesis is true on a statistical basis, it is nevertheless of interest to look for particular examples in which gene sequences seem to have been under directional selection in particular organisms. One way of doing this is to look for genes in which there is a large ratio of non-synonymous to synonymous substitutions (more details in Section 11.2.3). Such genes are rare, although the BRCA1 gene is actually an example where there seems to have been adaptive evolution in the lineage of humans and chimpanzees since their divergence from gorillas (Huntley et al . 2000). Kreitman and Comeron (1999) have also reviewed recent studies looking for evidence of selection acting in coding sequences.

  We will conclude this section with a brief mention of the phenomenon known as codon bias. We might expect that synonymous substitutions would be a prime case where the neutral theory was likely to apply. However, there is considerable evidence that weak selection can also act between synonymous codons. As a result, synonymous codons are not all used with equal frequency in gene sequences,i.e., there is a bias in the usage of codons, such that some codons are apparently preferred over others. One reason for this is purely mutational. If mutation rates between the four bases are different, then the expected frequencies of the bases at the third codon position will be different from one another, even in the absence of selection. However, a key observation is that codon usage sometimes differs between genes in the same genome. It is often found that genes that are highly expressed are more biased in their codon usage (i.e., they use the preferred codons more frequently) than less strongly expressed genes. This is thought to be due to selection for increasing the efficiency of the translation process. It is known that certain tRNAs are present in the cell at higher concentration than others, and that the preferred codons seem to correspond to the anticodons of the tRNAs that are most frequent. Using the preferred codons therefore means there is less time spent during translation waiting for an appropriate tRNA to come along. Codon bias is quite a subtle problem because it arises as a result of weak selective effects that may not be the same in all situations. For interesting recent examples in this field, see Musto et al

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  The Princeton Guide to Evolution

  • David A. Baum, Douglas J. Futuyma, Hopi E. Hoekstra, Richard E. Lenski, Allen J. Moore, Catherine L. Peichel, Dolph Schluter, Michael C. Whitlock, David A. Baum, Douglas J. Futuyma, Hopi E. Hoekstra, Richard E. Lenski, Allen J. Moore, Catherine L. Peichel, Dolph Schluter, Michael C. Whitlock(Authors)
  • 2013(Publication Date)
  • Princeton University Press

    (Publisher)

  all new mutations, be they deleterious, neutral, or adaptive, are lost and lost quickly.

  2. THE NEUTRAL THEORY OF MOLECULAR EVOLUTION

  To detect adaptation with confidence, much more specific, quantitative expectations under the null model of no adaptation must be generated. The neutral theory, most commonly associated with Motoo Kimura, provides a good example of such expectations (see chapter V.1 ). The neutral theory postulates that practically all mutations are either deleterious or neutral and that practically all detectable polymorphisms and all substitutions are due to Neutral Mutations. Note that the second postulate is much more restrictive than the first. Even if the adaptive mutations are vanishingly rare compared with neutral or deleterious mutations, they still could easily contribute to the majority of substitutions. This is because the probability of fixation of a new neutral mutation is the reciprocal of the population size (N) (technically of the long-term effective population size Ne ), while the probability of fixation of a strongly advantageous mutation is roughly equal to its selective benefit (as mentioned above) and the latter can be much, much larger. For instance, in Drosophila melanogaster, where the (long-term effective) population size is roughly 1 million, a mutation that provides 1 percent benefit has a 10,000 times greater chance of fixation than a neutral mutation. This implies that if adaptive mutations of 1 percent advantage were even 1000 times less frequent than neutral ones, they would still correspond to about 90 percent of all substitutions. The neutral theory thus claims that the increased chance of fixation of adaptive mutations does not compensate for their relative rarity.

  Figure 1. Expected patterns of polymorphism (P) and divergence (D) and functional (subscript n) and neutral (subscript s) sites. (A) The expectation under the neutral theory. Mutations at functional sites come in two classes, either lethal

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  Medical Genetics at a Glance

  • Dorian J. Pritchard, Bruce R. Korf(Authors)
  • 2013(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  25 Types of genetic alterations

  Overview

  Mutations are permanent modifications in the base sequence of DNA. They can occur at the level of one or a few bases of DNA, as point mutations involving substitution, deletion or insertion. Substitution of a purine by another purine or of a pyrimidine by another primidine is a transition, exchanges of purines and pyrimidines are transversions. At the level of a gene, mutations involve dozens to thousands of bases. At the genomic level muta­tions include deletions or dupli­cations of hundreds of thousands to millions of bases, up to chromosome rearrangements and aneuploidies (Chapter 36 ). Copy number variation (CNV) involves large deletions and insertions of various lengths created by unequal crossing over between misaligned segments of repetitious DNA or by non-homologous end-joining. Unequal crossing over is the origin of X-linked anomalous colour vision (see Chapter 11 ).

  Activation of enhancers and silencers (Chapter 21 ) can cause phenotypic variation in expression of the genes they control.

  Dynamic mutations involve expansion of triplet repeat sequences (see Chapter 28 ), and can undergo further expansion or contraction from generation to generation.

  Substitutions, deletions, insertions, frameshifts and duplications

  Substitution involves replacement of a base pair. If the amino acid encoded by the new codon is the same, it is a silent mutation, or if different, a missense mutation (see Figures 25.1, 24.1). Some missense mutations do not alter the chemical properties of the protein (conservative mutations), whereas others have a deleterious effect. In some cases, though, heterozygosity of a deleterious mutation may create selective advantage. A notable example is the substitution of the sixth codon in the β-globin chain responsible for sickle cell anaemia (see Chapter 29 ), which in heterozygotes confers resistance to malaria.

  Substitution can create a STOP codon, causing translation to come to a premature halt. This is called a premature termination or nonsense (‘non-sense’) mutation

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  Annual Reviews Of Computational Physics Vii

  • Dietrich Stauffer(Author)
  • 2000(Publication Date)
  • World Scientific

    (Publisher)

  This way, models of molecular evolution may appear next to those used in animal breeding. This should not be misunderstood as neglect of the historical context or the biological motivation; however, it is felt that the classical and molecular fields should (and do!) intermingle, and much can be gained by considering their mutual relationships. 4.1. Mutation models If the genotype is a collection of sites, it is usually assumed that all sites mutate independently and experience the same transition probabilities. With binary variables at the sites, mutation is either chosen symmetric or unidirectional. Biological Evolution Through Mutation, Selection, and ... 221 Symmetric mutation is more adequate for the molecular context, whereas uni-directional mutation is often used in the classical regime. The notion behind the latter is that, actually, multiple alleles per site are assumed, but they are lumped into a (small) wild type and a (large) mutant class, where muta-tions from wild type to mutant are predominant and back mutations negligible, due to sheer entropic reasons. With a £ {+, — } L and symmetric mutation with probability p per site at every reproduction event, the mutation probability from

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  Quantitative Biosciences

  Dynamics across Cells, Organisms, and Populations

  • Joshua S. Weitz(Author)
  • 2024(Publication Date)
  • Princeton University Press

    (Publisher)

  cerevisiae 1 A ABs 1 ABs 1 C Figure 4.14: A sequence of beneficial mutations and neutral muta- tions that hitchhike offer a parsimonious explanation of the con- current rise of multiple mutations in experimentally evolving yeast populations. Reproduced from Lang et al. (2013). cohorts to partial fixation. This is the subject of one of the homework problems, but at least some additional evidence is worthwhile to consider. At first, a beneficial mutation appears and begins to sweep through the population. Call this genome A. But then another mutation appears on a different genome (genome u), potentially with Neutral Mutations in the back- ground, and genome u begins to outcom- pete the original sweeping genome. How- ever, then a new mutation appears in the A background—call this genome AB—and it (and its Neutral Mutations) recovers and outcom- petes u and its mutations. This process—called clonal interference—can repeat many times over. Clonal interference denotes the fact that dif- ferent “clones” with different beneficial muta- tions can compete (i.e., interfere) with what might otherwise be the selective sweep of a focal lineage. One hallmark is that nonNeutral Mutations recur time and again in the evolu- tionary history (i.e., repeatably) even as neutral 110 Chapter 4 mutations appear by chance and sweep (i.e., contingently). The sweeping of neutral muta- tions is called genetic hitchhiking. Figure 4.14 shows precisely this point, in which groups of mutations appear at nearly precisely the same time and change in frequency in nearly pre- cisely the same shape. Many of these mutations are neutral. One way to verify the presence of clonal interference is to evaluate if the genomic sites of nonNeutral Mutations repeat. (Hint: They do.) Likewise one way to verify the presence of genetic hitchiking is to eval- uate whether or not the sites of synonymous mutations repeat.

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  Molecular Biology

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

    (Publisher)

  silent mutation is an alteration in the DNA sequence that has no effect on the operation of the cell and is therefore not so much silent as invisible from the outside. In other words, silent mutations do not alter the phenotype. One obvious kind of silent mutation is a base change occurring in the non-coding DNA between genes. Therefore, no genes are damaged and no proteins are altered. Higher organisms possess intervening sequences, the introns, within many of their genes. Since introns are cut out and discarded when the messenger RNA is made, most alterations to the sequence of an intron will not affect the final protein.

  Many mutations have no effect on the phenotype—they are “silent”.

  Not all base changes in an intron are harmless. Changes in the few critical bases at the splice recognition sites will result in failure to splice out the intron or in aberrant splicing. This will give a severely damaged protein product when the misspliced mRNA is translated. Further, many of the small nucleolar RNAs are derived from introns in other genes (Ch.12 ). In addition, occasional cases are known where an intronis needed to guide base modifications to a neighboring exon (seeCh. 12 ). Nevertheless, most base changes within most introns are silent mutations.

  silent mutation

  An alteration in the DNA sequence that has no effect on the phenotype

  The third main type of silent mutation occurs within the coding region of a gene and does get passed on to the messenger RNA. Remember that each codon, or group of three bases, is translated into a single amino acid in the final protein product. However, because there are 64 different codons, most of the 20 possible amino acids have more than one codon (see Codon Table,Fig. 8.02 ). So a base change that converts the original codon into another codon that codes for the same amino acid will have no effect on the final structure of the protein.

  Since many amino acids have several codons, changing the third base of a codon often leaves the amino acid unchanged.

  For example, the amino acid alanine has four codons: GCU, GCC, GCA and GCG. (Note that the sequences are discussed in RNA language;these are the codons as found on mRNA.) Since they all have GC as the first two bases, any codon of the form GCN (N = any base) will give alanine. A mutation in an original GCC sequence changing the last C to an A or a G or a U results in change in the sequence of the codon, but there is no change in the amino acid produced (alanine) in the resulting protein. Many other amino acids (such as valine, threonine and glycine) also have sets of four codons in which the last base does not matter. This pattern is referred to as third base redun-dancy

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