Information

4.1: Origins of Mutations - Biology

4.1: Origins of Mutations - Biology


We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

Types of mutations

Mutations may involve the loss (deletion), gain (insertion) of one or more base pairs, or else the substitution of one or more base pairs with another DNA sequence of equal length. These changes in DNA sequence can arise in many ways, some of which are spontaneous and due to natural processes, while others are induced by humans intentionally (or unintentionally) using mutagens. There are many ways to classify mutagens, which are the agents or processes that cause mutation or increase the frequency of mutations. We will classify mutagens here as being (1) biological, (2) chemical, or (3) physical.

Mutations of biological origin

A major source of spontaneous mutation is errors that arise during DNA replication. DNA polymerases are usually very accurate in adding a base to the growing strand that is the exact complement of the base on the template strand. However, occasionally, an incorrect base is inserted. Usually, the machinery of DNA replication will recognize and repair mispaired bases, but nevertheless, some errors become permanently incorporated in a daughter strand, and so become mutations that will be inherited by the cell’s descendents (Figure (PageIndex{1})).

Another type of error introduced during replication is caused by a rare, temporary misalignment of a few bases between the template strand and daughter strand (Figure (PageIndex{2})). This strand-slippage causes one or more bases on either strand to be temporarily displaced in a loop that is not paired with the opposite strand. If this loop forms on the template strand, the bases in the loop may not be replicated, and a deletion will be introduced in the growing daughter strand. Conversely, if a region of the daughter strand that has just been replicated becomes displaced in a loop, this region may be replicated again, leading to an insertion of additional sequence in the daughter strand, as compared to the template strand.

Consequences: Regions of DNA that have several repeats of the same few nucleotides in a row are especially prone to this type of error during replication. Thus regions with short-sequence repeats (SSRs) are tend to be highly polymorphic, and are therefore particularly useful in genetics. They are called microsatellites.

Mutations can also be caused by the insertion of viruses, transposable elements (transposons), see below, and other types of DNA that are naturally added at more or less random positions in chromosomes. The insertion may disrupt the coding or regulatory sequence of a gene, including the fusion of part of one gene with another. These insertions can occur spontaneously, or they may also be intentionally stimulated in the laboratory as a method of mutagenesis called transposon-tagging. For example, a type of transposable element called a P element is widely used in Drosophila as a biological mutagen. T-DNA, which is an insertional element modified from a bacterial pathogen, is used as a mutagen in some plant species.

Mutations due to Transposable Elements

Transposable elements (TEs) are also known as mobile genetic elements, or more informally as jumping genes. They are present throughout the chromosomes of almost all organisms. These DNA sequences have a unique ability to be cut or copied from their original location and inserted into new locations in the genome. This is called transposition. These insert locations are not entirely random, but TEs can, in principle, be inserted into almost any region of the genome. TEs can therefore insert into genes, disrupting its function and causing a mutation. Researchers have developed methods of artificially increasing the rate of transposition, which makes some TEs a useful type of mutagen. However, the biological importance of TEs extends far beyond their use in mutant screening. TEs are also important causes of disease and phenotypic instability, and they are a major mutational force in evolution.

There are two major classes of TEs in eukaryotes (Figure (PageIndex{3})).

  • Class I elements include retrotransposons; these transpose by means of an RNA intermediate. The TE transcript is reverse transcribed into DNA before being inserted elsewhere in the genome through the action of enzymes such as integrase.
  • Class II elements are known also as transposons. They do not use reverse transcriptase or an RNA intermediate for transposition. Instead, they use an enzyme called transposase to cut DNA from the original location and then this excised dsDNA fragment is inserted into a new location. Note that the name transposon is sometimes used incorrectly to refer to any type of TEs, but in this book we use transposon to refer specifically to Class II elements.

TEs are relatively short DNA sequences (100-10,000 bp), and encode no more than a few proteins (if any). Normally, the protein-coding genes within a TE are all related to the TE’s own transposition functions. These proteins may include reverse transcriptase, transposase, and integrase. However, some TEs (of either Class I or II) do not encode any proteins at all. These non-autonomous TEs can only transpose if they are supplied with enzymes produced by other, autonomous TEs located elsewhere in the genome. In all cases, enzymes for transposition recognize conserved nucleotide sequences within the TE, which dictate where the enzymes begin cutting or copying.

The human genome consists of nearly 45% TEs, the vast majority of which are families of Class I elements called LINEs and SINEs. The short, Alu type of SINE occurs in more than one million copies in the human genome (compare this to the approximately 21,000, non-TE, protein-coding genes in humans). Indeed, TEs make up a significant portion of the genomes of almost all eukaryotes. Class I elements, which usually transpose via an RNA copy-and-paste mechanism, tend to be more abundant than Class II elements, which mostly use a cut-and-paste mechanism. But even the cut-paste mechanism can lead to an increase in TE copy number. For example, if the site vacated by an excised transposon is repaired with a DNA template from a homologous chromosome that itself contains a copy of a transposon, then the total number of transposons in the genome will increase.

Besides greatly expanding the overall DNA content of genomes, TEs contribute to genome evolution in many other ways. As already mentioned, they may disrupt gene function by insertion into a gene’s coding region or regulatory region. More interestingly adjacent regions of chromosomal DNA are sometimes mistakenly transposed along with the TE; this can lead to gene duplication. The duplicated genes are then free to evolve independently, leading in some cases to the development of new functions. The breakage of strands by TE excision and integration can disrupt genes, and can lead to chromosome rearrangement or deletion if errors are made during strand rejoining. Furthermore, having so many similar TE sequences distributed throughout a chromosome sometimes allows mispairing of regions of homologous chromosomes at meiosis, which can cause unequal crossing-over, resulting in deletion or duplication of large segments of chromosomes. Thus, TEs are a potentially important evolutionary force, and may not be included as merely “junk DNA”, as they once were.


Gene mutation: a change to the base sequence of a gene.

Sickle cell anaemia is a genetic disease that affects red blood cells in the body. It is due to a mutation on the Hb gene which codes for a polypeptide of 146 amino acids which is part of haemoglobin (haemoglobin is an important protein component in red blood cells). In sickle cell anaemia the codon GAG found in the normal Hb gene is mutated to GTG. This is called a base substitution mutation as adenine (A) is replaced by thymine (T). This means that when the mutated gene is transcribed, a codon in the messenger RNA will be different. Instead of the normal codon GAG, the messenger RNA will contain the codon GUG. This in turn will result in a mistake during translation. In a healthy individual the codon GAG on the messenger RNA matches with the anticodon CUC on the transfer RNA carrying the amino acid glutamic acid. However, if the mutated gene is present then GUG on the messenger RNA matches with the anticodon CAC on the transfer RNA which carries the amino acid valine. So the base substitution mutation has caused glutamic acid to be replaced by valine on the sixth position on the polypeptide. This results in haemoglobin S being present in red blood cells instead of the normal haemoglobin A. This has an effect on the phenotype as instead of normal donut shaped red blood cells being produced some of the red blood cells will be sickle shaped. As a result these sickle shaped red blood cells cannot carry oxygen as efficiently as normal red blood cells would. However, there is an advantage to sickle cell anemia. The sickle cell red blood cells give resistance to malaria and so the allele Hb s on the Hb gene which causes sickle cell anemia is quite common in parts of the world where malaria is found as it provides an advantage over the disease.


Contents

Three classical hypotheses Edit

Viruses are ancient. Studies at the molecular level have revealed relationships between viruses infecting organisms from each of the three domains of life, suggesting viral proteins that pre-date the divergence of life and thus infecting the last universal common ancestor. [3] This indicates that some viruses emerged early in the evolution of life, [4] and that they have probably arisen multiple times. [5] It has been suggested that new groups of viruses have repeatedly emerged at all stages of evolution, often through the displacement of ancestral structural and genome replication genes. [6]

There are three classical hypotheses on the origins of viruses and how they evolved:

  • Virus-first hypothesis: Viruses evolved from complex molecules of protein and nucleic acid before cells first appeared on earth. [1][2] By this hypothesis, viruses contributed to the rise of cellular life. [7] This is supported by the idea that all viral genomes encode proteins that do not have cellular homologs. The virus-first hypothesis has been dismissed by some scientists because it violates the definition of viruses, in that they require a host cell to replicate. [1]
  • Reduction hypothesis (degeneracy hypothesis): Viruses were once small cells that parasitized larger cells. [8][9] This is supported by the discovery of giant viruses with similar genetic material to parasitic bacteria. However, the hypothesis does not explain why even the smallest of cellular parasites do not resemble viruses in any way. [7]
  • Escape hypothesis (vagrancy hypothesis): Some viruses evolved from bits of DNA or RNA that "escaped" from the genes of larger organisms. [10] This does not explain the structures that are unique to viruses and are not seen anywhere in cells. It also does not explain the complex capsids and other structures of virus particles. [7]

Virologists are in the process of re-evaluating these hypotheses. [6] [11] [12]

Later hypotheses Edit

  • Coevolution hypothesis (Bubble Theory): At the beginning of life, a community of early replicons (pieces of genetic information capable of self-replication) existed in proximity to a food source such as a hot spring or hydrothermal vent. This food source also produced lipid-like molecules self-assembling into vesicles that could enclose replicons. Close to the food source replicons thrived, but further away the only non-diluted resources would be inside vesicles. Therefore, evolutionary pressure could push replicons along two paths of development: merging with a vesicle, giving rise to cells and entering the vesicle, using its resources, multiplying and leaving for another vesicle, giving rise to viruses. [13]
  • Chimeric-origins hypothesis: Based on the analyses of the evolution of the replicative and structural modules of viruses, a chimeric scenario for the origin of viruses was proposed in 2019. [6] According to this hypothesis, the replication modules of viruses originated from the primordial genetic pool, although the long course of their subsequent evolution involved many displacements by replicative genes from their cellular hosts. By contrast, the genes encoding major structural proteins evolved from functionally diverse host proteins throughout the evolution of the virosphere. [6] This scenario is distinct from each of the three traditional scenarios but combines features of the Virus-first and Escape hypotheses.

One of the problems for studying viral origins and evolution is the high rate of viral mutation, particularly the case in RNA retroviruses like HIV/AIDS. A recent study based on comparisons of viral protein folding structures, however, is offering some new evidence. Fold Super Families (FSFs) are proteins that show similar folding structures independent of the actual sequence of amino acids, and have been found to show evidence of viral phylogeny. The proteome of a virus, the viral proteome, still contains traces of ancient evolutionary history that can be studied today. The study of protein FSFs suggests the existence of ancient cellular lineages common to both cells and viruses before the appearance of the 'last universal cellular ancestor' that gave rise to modern cells. Evolutionary pressure to reduce genome and particle size may have eventually reduced viro-cells into modern viruses, whereas other coexisting cellular lineages eventually evolved into modern cells. [14] Furthermore, the long genetic distance between RNA and DNA FSFs suggests that the RNA world hypothesis may have new experimental evidence, with a long intermediary period in the evolution of cellular life.

Definitive exclusion of a hypothesis on the origin of viruses is difficult to make on Earth given the ubiquitous interactions between viruses and cells, and the lack of availability of rocks that are old enough to reveal traces of the earliest viruses on the planet. From an astrobiological perspective, it has therefore been proposed that on celestial bodies such as Mars not only cells but also traces of former virions or viroids should be actively searched for: possible findings of traces of virions in the apparent absence of cells could provide support for the virus-first hypothesis. [15]

Viruses do not form fossils in the traditional sense, because they are much smaller than the finest colloidal fragments forming sedimentary rocks that fossilize plants and animals. However, the genomes of many organisms contain endogenous viral elements (EVEs). These DNA sequences are the remnants of ancient virus genes and genomes that ancestrally 'invaded' the host germline. For example, the genomes of most vertebrate species contain hundreds to thousands of sequences derived from ancient retroviruses. These sequences are a valuable source of retrospective evidence about the evolutionary history of viruses, and have given birth to the science of paleovirology. [16]

The evolutionary history of viruses can to some extent be inferred from analysis of contemporary viral genomes. The mutation rates for many viruses have been measured, and application of a molecular clock allows dates of divergence to be inferred. [17]

Viruses evolve through changes in their RNA (or DNA), some quite rapidly, and the best adapted mutants quickly outnumber their less fit counterparts. In this sense their evolution is Darwinian. [18] The way viruses reproduce in their host cells makes them particularly susceptible to the genetic changes that help to drive their evolution. [19] The RNA viruses are especially prone to mutations. [20] In host cells there are mechanisms for correcting mistakes when DNA replicates and these kick in whenever cells divide. [20] These important mechanisms prevent potentially lethal mutations from being passed on to offspring. But these mechanisms do not work for RNA and when an RNA virus replicates in its host cell, changes in their genes are occasionally introduced in error, some of which are lethal. One virus particle can produce millions of progeny viruses in just one cycle of replication, therefore the production of a few "dud" viruses is not a problem. Most mutations are "silent" and do not result in any obvious changes to the progeny viruses, but others confer advantages that increase the fitness of the viruses in the environment. These could be changes to the virus particles that disguise them so they are not identified by the cells of the immune system or changes that make antiviral drugs less effective. Both of these changes occur frequently with HIV. [21]

Many viruses (for example, influenza A virus) can "shuffle" their genes with other viruses when two similar strains infect the same cell. This phenomenon is called genetic shift, and is often the cause of new and more virulent strains appearing. Other viruses change more slowly as mutations in their genes gradually accumulate over time, a process known as antigenic drift. [23]

Through these mechanisms new viruses are constantly emerging and present a continuing challenge in attempts to control the diseases they cause. [24] [25] Most species of viruses are now known to have common ancestors, and although the "virus first" hypothesis has yet to gain full acceptance, there is little doubt that the thousands of species of modern viruses have evolved from less numerous ancient ones. [26] The morbilliviruses, for example, are a group of closely related, but distinct viruses that infect a broad range of animals. The group includes measles virus, which infects humans and primates canine distemper virus, which infects many animals including dogs, cats, bears, weasels and hyaenas rinderpest, which infected cattle and buffalo and other viruses of seals, porpoises and dolphins. [27] Although it is not possible to prove which of these rapidly evolving viruses is the earliest, for such a closely related group of viruses to be found in such diverse hosts suggests the possibility that their common ancestor is ancient. [28]

Bacteriophage Edit

Escherichia virus T4 (phage T4) is a species of bacteriophage that infects Escherichia coli bacteria. It is a double-stranded DNA virus in the family Myoviridae. Phage T4 is an obligate intracellular parasite that reproduces within the host bacterial cell and its progeny are released when the host is destroyed by lysis. The complete genome sequence of phage T4 encodes about 300 gene products. [29] These virulent viruses are among the largest, most complex viruses that are known and one of the best studied model organisms. They have played a key role in the development of virology and molecular biology. The numbers of reported genetic homologies between phage T4 and bacteria and between phage T4 and eukaryotes are similar suggesting that phage T4 shares ancestry with both bacteria and eukaryotes and has about equal similarity to each. [30] Phage T4 may have diverged in evolution from a common ancestor of bacteria and eucaryotes or from an early evolved member of either lineage. Most of the phage genes showing homology with bacteria and eukaryotes encode enzymes acting in the ubiquitous processes of DNA replication, DNA repair, recombination and nucleotide synthesis. [30] These processes likely evolved very early. The adaptive features of the enzymes catalyzing these early processes may have been maintained in the phage T4, bacterial, and eukaryotic lineages because they were established well-tested solutions to basic functional problems by the time these lineages diverged.

Viruses have been able to continue their infectious existence due to evolution. Their rapid mutation rates and natural selection has given viruses the advantage to continue to spread. One way that viruses have been able to spread is with the evolution of virus transmission. The virus can find a new host through: [31]

  • Droplet transmission- passed on through body fluids (sneezing on someone)
    • An example is the influenza virus [32]
    • An example would be how viral meningitis is passed on [33]
    • An example is viral encephalitis [34]
    • Poliovirus is an example for this [35]
    • The smallpox virus is also an example for this [35]

    There are also some ideas behind the idea that virulence, or the harm that the virus does on its host, depends on a few factors. These factors also have an effect on how the level of virulence will change over time. Viruses that transmit through vertical transmission (transmission to the offspring of the host) will evolve to have lower levels of virulence. Viruses that transmit through horizontal transmission (transmission between members of the same species that don't have a parent-child relationship) will usually evolve to have a higher virulence. [36]


    Types of Mutations

    The DNA 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. The types of mutations include:

    • Silent mutation: Silent mutations cause a change in the sequence of bases in a DNA molecule, but do not result in a change in the amino acid sequence of a protein (Figure 1).
    • Missense mutation: This type of mutation is a change in one DNA base pair that results in the substitution of one amino acid for another in the protein made by a gene (Figure 1).
    • Nonsense mutation: A nonsense mutation is also a change in one DNA base pair. Instead of substituting one amino acid for another, however, the altered DNA sequence prematurely signals the cell to stop building a protein (Figure 1). This type of mutation results in a shortened protein that may function improperly or not at all.
    Figure: Some mutations do not change the sequence of amino acids in a protein. Some swap one amino acid for another. Others introduce an early stop codon into the sequence causing the protein to be truncated.

    Related Biology Terms

    • Chromosome – A part of DNA that carries genetic information.
    • Homologous – Having the same function or structure within a body, or between two species.

    1. Mutations like SCD, which sometimes have deadly side effects, do not become extinct due to natural selection because:
    A. The government wants them to stay.
    B. Mutations work outside of natural selection. Unlike traits, they cannot be bred out.
    C. They provide resistance or immunity to other, more serious illnesses.
    D. Mutations are a superbug that drugs cannot combat.

    2. Mutations are sometimes carried on the sex chromosomes, X and Y. Why might a male inherit a mutation carried by his mother, even though his mother does not have the mutation, herself?
    A. The male inherited the recessive mutation on his X chromosome, while his mother inherited the recessive mutation on one X chromosome and a dominant form of the gene on her other X chromosome.
    B. The male inherited the dominant mutation on his X chromosome, because his mother carried the dominant mutation on both of her X chromosomes.
    C. The male inherited the dominant mutation on his Y chromosome, because his mother carried the dominant mutation on her Y chromosome.
    D. The male inherited the dominant mutation on his Y chromosome, because his mother carried the recessive mutation on her Y chromosome.

    3. Male calico cats are rare because:
    A. The gene for fur color is carried on the X chromosome, and is inherited exclusively from the mother. The mother would have to carry both the gene for orange fur and the gene for black fur for her male offspring to be a calico.
    B. The gene for fur color is carried on the X chromosome, and male cats only have one X chromosome. A male cat would have to have two X chromosomes, or the Klinefelter’s syndrome mutation, to inherit both orange and black fur.
    C. The gene for fur color is carried on the X chromosome, and male cats do not always inherit the X chromosome. This is why there are so many albino male cats.
    D. The gene for fur color is carried on the Y chromosome, and male cats do not usually inherit two Y chromosomes. A male cat must therefore have an XYY genotype to be a calico.


    Molecular analysis of insertion/deletion mutations in protein 4.1 in elliptocytosis. II. Determination of molecular genetic origins of rearrangements.

    Department of Laboratory Medicine, University of California, San Francisco 94143.

    Department of Laboratory Medicine, University of California, San Francisco 94143.

    Find articles by Marchesi, S. in: JCI | PubMed | Google Scholar

    Department of Laboratory Medicine, University of California, San Francisco 94143.

    Department of Laboratory Medicine, University of California, San Francisco 94143.

    Department of Laboratory Medicine, University of California, San Francisco 94143.

    Department of Laboratory Medicine, University of California, San Francisco 94143.

    Find articles by Mohandas, N. in: JCI | PubMed | Google Scholar

    Protein 4.1 is an approximately 80-kD structural protein in the membrane skeleton which underlies and supports the erythrocyte plasma membrane. The preceding companion paper presents a biochemical study of two abnormal protein 4.1 species from individuals with the red blood cell disorder, hereditary elliptocytosis. These variants, "protein 4.1(68/65)" and "protein 4.1(95)," have altered molecular weights due to internal deletions and duplications apparently localized around the spectrin-actin binding domain. Here we use polymerase chain reaction (PCR) techniques to clone and sequence the corresponding mutant reticulocyte mRNAs, and correlate the deletion/duplication end points with exon boundaries of the gene. Protein 4.1(68/65) mRNA lacks sequences encoding the functionally important spectrin-actin binding domain due to a 240 nucleotide (nt) deletion spanning the codons for Lys407-Gly486. Protein 4.1(95) mRNA encodes a protein with two spectrin-actin binding domains by virtue of a 369 nt duplication of codons for Lys407-Gln529. These deletions and duplications correspond to gene rearrangements involving three exons encoding 21, 59, and 43 amino acids, respectively. The duplicated 21 amino acid exon in the 4.1(95) gene retains its proper tissue-specific expression pattern, being spliced into reticulocyte 4.1 mRNA and out of lymphocyte 4.1 mRNA.

    Click on an image below to see the page. View PDF of the complete article


    Molecular analysis of insertion/deletion mutations in protein 4.1 in elliptocytosis. II. Determination of molecular genetic origins of rearrangements

    Protein 4.1 is an approximately 80-kD structural protein in the membrane skeleton which underlies and supports the erythrocyte plasma membrane. The preceding companion paper presents a biochemical study of two abnormal protein 4.1 species from individuals with the red blood cell disorder, hereditary elliptocytosis. These variants, "protein 4.1(68/65)" and "protein 4.1(95)," have altered molecular weights due to internal deletions and duplications apparently localized around the spectrin-actin binding domain. Here we use polymerase chain reaction (PCR) techniques to clone and sequence the corresponding mutant reticulocyte mRNAs, and correlate the deletion/duplication end points with exon boundaries of the gene. Protein 4.1(68/65) mRNA lacks sequences encoding the functionally important spectrin-actin binding domain due to a 240 nucleotide (nt) deletion spanning the codons for Lys407-Gly486. Protein 4.1(95) mRNA encodes a protein with two spectrin-actin binding domains by virtue of a 369 nt duplication of codons for Lys407-Gln529. These deletions and duplications correspond to gene rearrangements involving three exons encoding 21, 59, and 43 amino acids, respectively. The duplicated 21 amino acid exon in the 4.1(95) gene retains its proper tissue-specific expression pattern, being spliced into reticulocyte 4.1 mRNA and out of lymphocyte 4.1 mRNA.


    Appendix II - A favorable mutation, journal abstract

    Arterioscler Thromb Vasc Biol 1998 Apr18(4):562-567. "PAI-1 plasma levels in a general population without clinical evidence of atherosclerosis: relation to environmental and genetic determinants," by Margaglione M, Cappucci G, d'Addedda M, Colaizzo D, Giuliani N, Vecchione G, Mascolo G, Grandone E, Di Minno G Unita' di Trombosi e Aterosclerosi, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.

    Plasminogen activator inhibitor-1 (PAI-1) plasma levels have been consistently related to a polymorphism (4G/5G) of the PAI-1 gene. The renin-angiotensin pathway plays a role in the regulation of PAI-1 plasma levels. An insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been related to plasma and cellular ACE levels. In 1032 employees (446 men and 586 women 22 to 66 years old) of a hospital in southern Italy, we investigated the association between PAI-1 4G/5G and the ACE I/D gene variants and plasma PAI-1 antigen levels. None of the individuals enrolled had clinical evidence of atherosclerosis. In univariate analysis, PAI-1 levels were significantly higher in men (P<.001), alcohol drinkers (P<.001), smokers (P=.009), and homozygotes for the PAI-1 gene deletion allele (4G/4G) (P=.012). Multivariate analysis documented the independent effect on PAI-1 plasma levels of body mass index (P<.001), triglycerides (P<.001), sex (P<.001), PAI-1 4G/5G polymorphism (P=.019), smoking habit (P=.041), and ACE I/D genotype (P=.042). Thus, in addition to the markers of insulin resistance and smoking habit, gene variants of PAI-1 and ACE account for a significant portion of the between-individual variability of circulating PAI-1 antigen concentrations in a general population without clinical evidence of atherosclerosis. [Full text]


    Notes on Mutation: Meaning and Historical Account

    The offsprings resemble their parents in one or several respects, yet there are differences between the two. These differences, whether large or small, are called variations. Some of the variations may be induced by environment, while others may be hereditary. Generally, the variations caused by environment are not permanent, hence non-heritable.

    But the variations which appear due to changes in the hereditary mechanism are permanent and heritable. Sudden appearance of marked heritable variation in the nature of any organism in ordinary sense is known as mutation and the offsprings with unusual variability in characters are called mutants. A mutant individual or cell is one in which the changed phenotype is attributable to mutated gene or genes.

    Many other definitions for mutation have been proposed from time to time by different biologists. Some are as under:

    1. Sudden appearance of new hereditary character in the progenies of plants and animals was referred to as ‘sport’ or mutation by Darwin.

    2. In the broad sense, it covers “any heritable change in the genotype” (Macromutation). In the narrower sense, “mutation is a change of gene” (micromutation) (Sinnot and others).

    3. According to Bateson, “mutation is discontinuous variation”.

    4. According to De Vries, “mutations are sudden and drastic heritable changes not traceable or ascribable to segregation or recombination”.

    5. Stebbins describes mutation as discontinuous chromosomal change with genetic effect. He further states that the chromosomal change refers to chemical change in a small part of its chromomere, as well as to alteration of its physical structure.

    6. Amatto and Otto (1956) have defined mutation as a change in the heredity constitution of a given species.

    Notes # Historical Account of Mutation:

    Little was known about mutation before 19th century. It was Darwin who first noticed several sudden changes in the organisms in nature. He called those changes as ‘sports’. Several years after Darwin, Bateson marked that some variations were not continuous.

    They were called discontinuous variations. Hugo De Vries (Fig. 22.1), one of the three persons who rediscovered Mendel’s laws of inheritance, observed in 1901 sudden changes in Oenothera lamarkiana.

    In Oenothera lamarkiana, gigas (large size), nanella (dwarf) and many other unusual changes, such as, changes in the colour and shape of flowers were marked by him. The new forms, he observed, differed in appearance from the normal forms and apparently they arose in small numbers in each generation.

    On the basis of those observations he proposed a general theory of species formation by means of sudden discontinuous changes.

    De Vries called such sudden changes as mutations. His observations were published in a book entitled. The Mutation Theory. Simultaneously several unique cases of mutation had been reported in nature, Ancon sheep (Fig. 22.2), one of the most interesting cases of mutation was first noticed in England.

    The ancon sheep had a short leg (an unusual feature). That type appeared suddenly in the flock of sheep, existed for several years and then disappeared.

    Again after eighty years, they reappeared in Norway and since then they are existing in some European countries. Besides these, many other remarkable cases of mutation have been noticed in both plants and animals. In 1904, Morgan reported white eyed Drosophila melanogaster in the population of red eye flies.

    The sudden occurrence of Haemophilia disease in the royal family (Queen Victoria’s family) of England deserves special mention here. Queen Victoria came from a family in which Haemophilia A as not known, but suddenly the disease appeared in some of her sons and subsequently in several sons of her daughters.

    Why did it appear? Perhaps, because something went wrong with the genetic machinery of one of the parents or apparently mutation to Haemophilia took place in germ cells of one of her parents so that she herself was already heterozygous for newly mutated character.

    Notes # Characteristics of Mutation:

    Originally the geneticists were of the opinion that mutations were spontaneous and random in effect, i.e., they were occasionally noticed but this statement seems to be contusive. Mutations may occur in an> cell at any stage of the life of an organism. Mutations occurring in reproductive cells (sperms and ova) are referred to as germinal mutations.

    In sexually reproducing species only the mutations arising in germ cells are transmitted to the future generation. Mutations arising in body cells other than germ cells are called somatic mutations.

    Somatic mutations, as for example, the fatal cancer of blood or the leukaemia, chronic myeloid, etc. arising in the body cells are not inherited as they affect only the mutant individuals and are not transmitted to future generations.

    Asexually propagated species in which somatic mutations occur may become established as mutant strains. Many new varieties of fruit trees have originated as “bud mutations “. In vegetatively propagated mutant plants, the gamete will be either normal or mutant depending on which cell forms germinal tissue.

    A mutation may be dominant or recessive, viable or lethal, sex-linked or autosomal. In diploid species, recessive mutation can produce bud mutation or mosaics only when the individual is heterozygous for the gene in question.

    Mosaic in snapdragon flower, which is half purple and half lavender, sometimes develops on a branch which, in addition to one or more such mosaic flowers, also bears several wholly purple or wholly lavender colour flowers.

    The plant itself was heterozygous for the recessive lavender genes. In some of the cells from which mosaic bud developed the normal allele has mutated to lavender. Dominant mutations may give rise to immediately observable bud, spores or mosaics.

    Mutations are detected when some heritable changes occur in the characters of an organism. Since the characters are governed by genes, any change in them directly reflects the change in the genes (gene mutation). So the relationship between a gene and a character is apparent only due to mutation.

    A gene mutation is also called point mutation. Sometimes, the mutations in genes do not result in any perceptible change in characters. Nevertheless, such changes are important from evolution point of view because they go on accumulating and have a cumulative effect on the phenotype.

    Normally, the original activity of a gene is lost due to mutation and this is the reason why original or wild type genes are dominant and mutant genes are recessive.

    In diploid organisms, for each character there are two genes located on two homologous chromosomes. As the mutation is a random process, the chance of simultaneous mutations in both the genes controlling a particular trait is very remote. If the mutation takes place in one of the two genes governing a particular trait, it results in heterozygosity because the other gene remains unaffected.

    In such a case the mutation may not be immediately expressed because of the presence of the wild or unmutated genes. It may be expressed in later generations in a small number of individuals which are homozygous for mutant gene.

    Recessive mutations perpetuate and are maintained in heterozygous state. In haploids, each character is usually governed by a single gene. So every mutation is expressed in them. Undesirable or unfit mutations are eliminated from the natural populations.

    The mutated gene differs from original one in chemical composition or structure. The mutated gene like the original one must be capable of accurate self-replication in mutated form. Any change away from the standard form is called forward mutation. Sometimes mutant genes change towards the standard form. This is called reverse mutation, reversion or back mutation.

    The truly mutated genes do not show reversion to the original gene. However, there are some rare exceptional cases in which reversion may be observed. Each individual gene mutates only very rarely, perhaps once in 1, 00,000 or once in a million cells but as the number of genes in the majority of the organisms is very high, the overall mutation frequency per generation may be considerable.

    Notes # Types of Mutation:

    Geneticists have classified mutations in different ways according to their convenience.

    Amatto (1950) considered three types of mutation:

    1. Gene mutation (Mutation at gene level),

    2. Chromosomal mutation (Mutation due to changes in the structure of chromosomes) and

    3. Genomatic mutation (Mutation due to change in genome or basic chromosome number).

    Recently Darlington and Mather have classified mutations into the following five types:

    1. Gene mutation (Mutation at gene level)

    2. Structural mutation (change in chromosome structure)

    Of the above mutational classes, numerical mutation and cytoplasmic and plastid mutations are described in separate chapters. Here only structural mutations and gene mutations will be discussed in detail.


    4.1: Origins of Mutations - Biology

    Mutation, Migration, Inbreeding, & Genetic Drift in natural populations

    How do mutation, migration, inbreeding, and genetic drift interact with selection ? Do they maintain or reduce variation?
    Can they maintain variation at a high level?
    What is their significance in population (short-term) & evolutionary (long-term) biology?

    (1) Mutation / selection equilibrium

    Deleterious alleles are maintained by recurrent mutation.
    A stable equilibrium (where q = 0) is reached
    when the rate of replacement (by mutation)
    balances the rate of removal (by selection).

    µ = frequency of new mutant alleles per locus per generation
    typical µ = 10 -6 : 1 in 1,000,000 gametes has new mutant
    _____
    then =(µ / s) [see derivation]

    Ex.: For a recessive lethal allele (s = 1) with a mutation rate of µ = 10 -6
    then = û = (10 -6 / 1.0) = 0.001

    mutational genetic load
    Lowering selection against alleles increases their frequency.
    Medical intervention has increased the frequency of heritable conditions
    in Homo (e.g., diabetes, myopia)
    Eugenics : modification of human condition by selective breeding
    'positive eugenics': encouraging people with "good genes" to breed
    'negative eugenics': discouraging people with 'bad genes'' from breeding
    e.g., immigration control, compulsory sterilization
    [See: S. J. Gould , " The Mismeasure of Man "]

    Is eugenics effective at reducing frequency of deleterious alleles?
    What proportion of 'deleterious alleles' are found in heterozygous carriers?

    (2pq) / 2q 2 = p/q 1/q (if q << 1)

    if s = 1 as above, ratio is 1000 / 1 : most of variation is in heterozygotes,
    not subject to selection

    (2) Migration / selection equilibrium

    Directional selection is balanced by influx of 'immigrant' alleles
    a stable 'equilibrium' can be reached iff migration rate constant.

    Consider an island adjacent to a mainland, with unidirectional migration to the island.
    The fitness values of the AA, AB, and BB genotypes differ in the two environments,
    so that the allele frequencies differ between the mainland (qm) and the island (qi).


    AA AB BB
    W0 W1 W2 q
    Island 1 1-t 1-2t qi 0
    Mainland 0 0 1 qm 1

    B has high fitness on mainland, and low fitness on island.
    [For this model only, allele A is semi-dominant to allele B,
    so we use t for the selection coefficient to avoid confusion]

    m = freq. of new migrants (with q m) as fraction of residents (with q i)
    if m << t qi = (m / t)(qm) [see derivation]

    Gene flow can hinder optimal adaptation of a population to local conditions.

    Ex: Water snakes (Natrix sipedon) live on islands in Lake Erie ( Camin & Ehrlich 1958 )
    Island Natrix mostly unbanded on adjacent mainland, all banded.
    Banded snakes are non-cryptic on limestone islands, eaten by gulls
    Suppose A = unbanded B = banded [AB are intermediate]
    Let qm = 1.0 ["B" allele is fixed on mainland]
    m = 0.05 [5% of island snakes are new migrants]
    t = 0.5 so W2 = 0 ["Banded" trait is lethal on island]
    then qi = (0.05/0.5)(1) = 0.05
    and Hexp = 2pq = (2)(0.95)(0.05) 10%
    i.e, about 10% of snakes show intermediate banding, despite strong selection

    => Recurrent migration can maintain a disadvantageous trait at high frequency.

    (3) Inbreeding / selection

    Inbreeding is the mating of (close) relatives
    or, mating of individuals with at least one common ancestor

    F ( Inbreeding Coefficient ) = prob. of " identity by descent ":
    Expectation that two alleles in an individual are
    exact genetic copies of an allele in the common ancestor
    or, proportion of population with two alleles identical by descent

    This is determined by the consanguinity (relatedness) of parents.

    Inbreeding reduces Hexp by a proportion F
    (& increases the proportion of homozygotes). [see derivation]

    f(AB) = 2pq (1-F)
    f(BB) = q 2 + Fpq
    f(AA) = p 2 + Fpq

    Inbreeding affects genotype proportions,
    inbreeding does not affect allele frequencies.

    Inbreeding increases the frequency of individuals
    with deleterious recessive genetic diseases by F/q [see derivation]

    Ex.: if q = 10 -3 and F = 0.10 , F/q = 100
    => 100-fold increase in f(BB) births

    Inbreeding coefficient of a population can be estimated from experimental data:

    F = ( 2pq - Hobs ) / 2pq [see derivation]

    Ex.: Selander (1970) studied structure of Mus house mice living in chicken sheds in Texas

    & q = 0.374 + (1/2)(0.400) = 0.574

    Then F = (0.489 - 0.400) / (0.489) = 0.182
    which is intermediate between Ffull-sib = 0.250
    & F1st-cousin = 0.125

    => Mice live in small family groups with close inbreeding
    [This is typical for small mammals]


    Paradoxes of inbreeding:
    Inbreeding is usually thought of as "harmful":
    inbreeding increase the probability that deleterious recessive alleles
    will come together in homozygous combinations
    "Harmful" alleles are reinforced
    Inbreeding depression : a loss of fitness in the short-term due to
    difficulty in conception, increased spontaneous abortion, pre- & peri-natal deaths
    Ex.: First-cousin marriages in Homo
    Two-fold increase in spontaneous abortion & infant mortality
    Every human carries 3

    Demonsration #2: Selection & inbreeding in small populations

    However, in combination with natural selection, inbreeding can be "advantageous":
    increases rate of evolution in the long-term (q 0 more quickly)
    deleterious alleles are eliminated more quickly.
    increases phenotypic variance (homozygotes are more common).
    advantageous alleles are also reinforced in homozygous form

    (4) Genetic Drift / selection

    Genetic Drift is stochastic q [unpredictable, random]
    (cf. deterministic q [predictable, due to selection, mutation, migration)

    Sewall Wright (1889 - 1989): " Evolution and the Genetics of Populations "

    Stochastic q > deterministic q in small populations:
    allele frequencies drift more rapidly in 'small' than 'large' populations.

    Drift is most noticeable if s 0, and/or N small (< 10) [N 1/s]
    genetic variance = q 2 = (q)(1 - q) / 2N
    if q = p = 0.5, then q 2 = 1 / 8N

    <> q drifts between generations ( within population variance decreases) [ DEMO ]

    eventually, allele is lost (q = 0) or fixed (q = 1) (if qi = 0.5 , 50:50 odds)

    q drifts among populations ( among population variance increases )
    eventually, half lose the allele, half fix it.

    Ex: [Demonstration #3]
    [Try: q = 0.5, W0 = W1 = W2 = 1.0, and N = 10, 50, 200, 1000
    repeat 10 trials each, note q at endpoint
    ]

    **=> Variation is 'fixed' or 'lost' & populations will diverge by chance <=**

    Evolutionary significance:
    "Gambler's Dilemma" : if you play long enough, you win or lose everything.
    All populations are finite: many are very small, somewhere or sometime.
    Evolution occurs on vast time scales: "one in a million chance" is a certainty.
    Reproductive success of individuals in variable: "The race is not to the swift . "

    What happens in the really long run?

    Effective Population Size (Ne)
    = size of an ' ideal ' population with same genetic variation (measured as H)
    as the observed 'real' population.
    = The ' real ' population behaves evolutionarily like one of size Ne :
    e.g., the population will drift like one of size Ne
    loosely , the number of breeding individuals in the population

    Consider three special cases where Ne < or << Nobs [the 'count' of individuals]:

    where Nm & Nf are numbers of breeding males & females, respectively.

    "harem" structures in mammals (Nm << Nf)
    Ex.: if Nm = 1 "alpha male" and Nf = 200
    then Ne = (4)(1)(200)/(1 + 200) 4
    A single male elephant seal (Mirounga) does most of the breeding
    Elephant seals have very low genetic variation

    eusocial (colonial) insects like ant & bees (Nf << Nm)
    Ex.: if Nf = 1 "queen" and Nm= 1,000 drones
    then Ne = (4)(1)(1,000)/(1 + 1,000) 4
    Hives are like single small families

    (2) Unequal reproductive success
    In stable population, Noffspring/parent = 1
    "Random" reproduction follows Poisson distribution (N = 1 1)
    (some parents have 0 , most have 1 , some have 2 , a few have 3 or more)

    X Ne = Reproductive strategy
    1 1 Nobs Breeding success is random
    1 0 2 x Nobs A zoo-breeding strategy
    1 >1 < Nobs K-strategy, as in Homo
    1 >>1 << Nobs r-strategy, as in Gadus

    (3) Population size variation over time

    Ne = harmonic mean of N = inverse of arithmetic mean of inverses
    [a harmonic mean is much closer to lowest value in series]
    n
    Ne = n / [ (1/Ni) ] where Ni = pop size in ith generation
    i=1

    Populations exist in changing environments:
    Populations are unlikely to be stable over very long periods of time
    10 -2 forest fire / 10 -3 flood / 10 -4 ice age

    Ex.: if typical N = 1,000,000 & every 100th generation N = 10 :
    then Ne = (100) / [(99)(10 -6 ) + (1)(1/10)] 100 / 0.1 = 1,000

    Founder Effect & Bottlenecks:
    Populations are started by (very) small number of individuals ( N=2 ),
    or undergo dramatic reduction in size ( N < 10 )).

    Ex.: Origin of Newfoundland moose (Alces):
    2 bulls + 2 cows at Howley in 1904
    [maximum 8 alleles / locus , likely less if single source population]
    [1 bull + 1 cow at Gander in 1878 didn't succeed].

    Population cycles: Hudson Bay Co. trapping records (Elton 1925)
    Population densities of lynx, hare, muskrat cycle over several orders of magnitude
    Lynx cycle appears to "chase" hare cycle

    The effect of drift on genetic variation in populations

    Larger populations are more variable (higher H) than smaller
    if s = 0 : H reflects balance between loss of alleles by drift
    and replacement by mutation

    Ex.: if µ = 10 -7 & Ne = 10 6 then Ne µ = 1 and Hexp = (0.4)/(0.4 + 1) = 0.29

    But typical Hobs 0.20 which suggests Ne 10 5
    Most natural populations have a much smaller effective size than their typically observed size.

    Ex.: Gadus morhua in W. Atlantic were confined to Flemish Cap during last Ice Age 8

    10 KYBP
    mtDNA sequence variation occurs as "star phylogeny":
    most variants are rare and related to a common surviving genotype
    Carr et al. 1995 estimated Ne = 3x10 4 as compared with Nob s 10 9
    Effective size is ca. 5 orders of magnitude smaller than observed

    Marshall et al. (2004) showed that " genome-types " at Flemish Cap are distinctive

    Stochastic effects may be as or more important than deterministic processes in long-term evolution.


    Watch the video: The different types of mutations. Biomolecules. MCAT. Khan Academy (May 2022).