Mutation PDF

Lesson 5  MUTATION Mutation an alteration or change in the sequence of nucleotides in DNA change can either bring no effect or are harmful, and small percentage can be beneficial happens when a different or wrong nucleotide is present o...

Lesson 5  MUTATION Mutation an alteration or change in the sequence of nucleotides in DNA change can either bring no effect or are harmful, and small percentage can be beneficial happens when a different or wrong nucleotide is present or incorporated in a DNA strand during replication or transcription causes variation and brings new species Mutagens are physical and chemical agents that cause direct change and damage in the DNA replication some mutagens act on the replication mechanism and chromosomal partition can be of physical, chemical, or biological origin Types of Mutagens 1. Physical mutagens include ionizing radiations (X-rays, gamma rays, and alpha particles) and ultraviolet radiations. 2. Chemical mutagens include reactive chemicals, deaminating agents, bromine, and benzene. 3. Biological mutagens include virus and bacteria. Mutation: Hereditary or Somatic 1. Hereditary Mutation inherited from a parent and is present throughout a person’s life occurs in every cell of the body also called germline mutation because it is present in germ cells or reproductive cells. A germ cell is either the egg or the sperm cell. When the germ cells unite, the zygote will carry the mutated gene. All the cells that descend from the zygote contain the mutated gene. 2.Somatic Mutation acquired mutation occurs at a point in a person’s lifetime it occurs only in specific cells commonly caused by external factors, such as exposure to radioactivity, drugs, and alcohol does not affect the egg and the sperm cell not passed onto offspring Module IV  72 E.g. mutations that occur in a somatic cell in the bone marrow can damage the cell, make the cell cancerous, or kill the cell Mutation: Spontaneous or Induced 1. Spontaneous Mutation Spontaneous mutation is a result of natural and random changes in the DNA structure. These are undetected and unrepaired errors during DNA replication or transcription. It occurs due to errors in the normal function of cellular enzymes such as DNA and RNA polymerases. It happens at an average rate of approximately one in a million. This rate is low because of cellular repair mechanisms. 2. Induced Mutation Not all mutations happen by themselves. Some mutations happen with the intervention of living and nonliving things. This type of mutation is called induced mutation. Exposure to mutagens causes induced mutation. Mutation may occur at chromosomal level (chromosomal mutation) or at gene or molecular level (gene mutation). Gene Mutations They are described as changes in the nucleotide sequences in the DNA. Changes in the encrypted message in the DNA may result to a different protein being translated. These causes problems in cellular metabolic processes where the correct protein is required. Types of Gene Mutation 1. Point Mutation Point mutation occurs when one DNA base is replaced by another, resulting in a change of codon in the RNA sequence. Transition /transversion categorization of point mutation a. Transition happens when adenine is replaced by guanine or vice versa (purine-purine). This also happens when cytosine is replaced by thymine or vice versa (pyrimidine-pyrimidine). b. Transversion occurs when either adenine or guanine is replaced by thymine or cytosine, respectively (purine-pyrimidine). Types of point mutation based on transcriptional property a. Missense Mutation In this mutation, mutated codon codes different amino acid (other than original). Since new amino acid coded by mutated codon is altered, the protein formed from it is also altered. Such protein can be less active or completely inactive. Module IV  73 If altered amino acids lie on active site of protein then such protein become completely non- functional. The missense mutation causes phenotypic change in organism. b. Silent Mutation It is also known as neutral mutation. It is the mutation in which mutated codon codes same amino acids as the original codon. Since the amino acid is same as original one, it does not affect the structure and composition of protein. A single nucleotide can change, but the new code specifies the same amino acid, resulting in an unmutated protein. c. Non-sense Mutation It is the mutation in which altered codon is stop codon or chain terminating codon. This causes the protein to be shortened because of the stop codon interrupting its normal code. It causes incomplete synthesis. Such incomplete protein is always non-functional. It brings greatest change in phenotype of an organism. 2. Frameshift Mutation It occurs as a result of addition or deletion of nucleotide in the sequence of DNA. Addition or deletion of nucleotides causes shift of the reading frame of mRNA. In an mRNA each codon is represented by three bases without punctuation and insertion or deletion of nucleotide changes the entire frame. So frame shift mutations bring greater phenotypic change than point mutation. Insertion or deletion of one or two base pair of nucleotides causes shift in frame. However, insertion or deletion of three base pairs adds or removes a whole codon, this results in addition of removal of single amino acid from polypeptide chain. a. Insertion It occurs when an extra base pair is added to a sequence of bases. b. Deletion It occurs when a base pair is deleted from a sequence. Chromosomal Mutations They are any change in the chromosome structure that affects the DNA sequence. They occur during mitosis or meiosis. The cell cycle processes such as crossing-over and recombination might have been affected, where the parts reunited in the wrong chromosome. They can cause severe abnormalities and malignancies. Module IV  74 Types of Chromosomal Mutations 1. Chromosomal Deletion Chromosomal deletion happens when a portion of the chromosome is deleted or removed. The figure in the next page shows the removal of one of the long arms of a chromosome. 2. Chromosomal Duplication Chromosomal duplication occurs when a portion of the chromosome is duplicated. In the figure, a segment or a portion of one of the long arms of a chromosome is duplicated, resulting in an abnormal chromosome. 3. Chromosomal Inversion Chromosomal inversion happens when portions of the chromosome are switched or inverted. This happens during chromosomal recombination where the portions were not reattached to their original positions. 4. Chromosomal Translocation Chromosomal translocation happens when a portion of a chromosome is transferred to another chromosome. The result is two chimeric chromosomes containing genetic material from each original chromosome. Types of Chromosomal Mutation Module IV  75 Nondisjunction is the failure of the chromosomes to separate, which produces daughter cells with abnormal numbers of chromosomes. Somatic human cells contain 23 paired chromosomes or 46 total chromosomes. Forty-six is considered the “diploid” number (2n), while 23 is considered the “haploid” number (1n) or half the diploid number. “Aneuploidy” refers to the presence of an abnormal number of chromosomes. Each type of aneuploidy can be attributed to nondisjunction during mitosis or meiosis. Monosomy (n-1) is a form of aneuploidy characterized by missing a single chromosome resulting in 45 total chromosomes. Trisomy (n+1) is another form of aneuploidy that has an extra chromosome resulting in 47 total chromosomes. Genetic Disorders due to Nondisjunction Autosomal Trisomies 1. Patau syndrome: Trisomy of chromosome 13 Clinical Features: Rocker-bottom feet, microphthalmia (abnormally small eyes), microcephaly (abnormally small head), polydactyly, holoprosencephaly, cleft lip and palate, congenital heart disease, and severe intellectual disability. Life expectancy is seldom longer than one year. 2. Edwards syndrome: Trisomy of chromosome 18 Clinical Features: Rocker-bottom feet, low set ears, micrognathia (abnormally small jaw), clenched hands with overlapping fingers, congenital heart disease, and severe intellectual disability. Life expectancy is normally less than one year. 3. Down syndrome: Trisomy of chromosome 21 Clinical Features: Single palmar crease, flat facies, prominent epicanthal folds, duodenal atresia, congenital heart disease, Hirschsprung disease, intellectual disability. Notably increased risk to develop Alzheimer's disease or leukemia. Life expectancy is about 60 years. Sex Chromosome Trisomies 1. Klinefelter Syndrome: An extra X chromosome in a male (47, XXY) Clinical Features: Tall, long extremities, gynecomastia, female hair distribution, testicular atrophy, developmental delay. 2. Triple X syndrome: An extra X chromosome in a female (47, XXX) Clinical Features: Phenotypically normal, some with unusually tall stature. Module IV  76 X chromosomes are inactivated as Barr bodies. Therefore, 2 extra Barr bodies are seen, though no clinical abnormalities result. 3. XYY syndrome: An extra Y chromosome in a male (47, XYY) Clinical Features: phenotypically normal, unusually tall stature. Most cases go undiagnosed due to a lack of clinical abnormalities. Sex Chromosome Monosomies 1. Turner Syndrome: Monosomy of X chromosome in a female (45, X) The only chromosomal monosomy that is compatible with life. Clinical Features: Unusually short stature, shield chest, congenital heart disease, webbed neck, horseshoe kidney, ovarian dysgenesis. The most common cause of primary amenorrhea. No Barr bodies are seen. Benefits of Mutation 1. Mutation Breeding It can be described as the purposeful application of mutations in plant breeding. Mutation breeding is commonly used to produce traits in crops such as larger seeds, new colors, or sweeter fruits, that either cannot be found in nature or have been lost during evolution. Mutations at the genome level, leading to changes in chromosome number are also of utmost importance in crop evolution and plant breeding. This mutation is broadly divided into allopolyploidy, autopolyploidy, and aneuploidy. Allopolyploidy is the result of a combination of genomes of two or more species and commonly arises through interspecific or intergeneric hybridization followed by the doubling of chromosomes. Evolution of many crops, such as wheat, soybean, cotton, and Brassica species, has taken this path. 2. Nylonase: Nylon bacteria The nylonase bacteria can eat molecules of nylon (nylon-6). The mutation in these bacteria involves insertion of a single nucleotide in the genetic material. It is estimated that this frameshift mutation might have occurred in the 1940s when nylon was invented. Nylonase can be used in wastewater treatment plants. 3. Almond Seeds Almond seeds from wild species contain amygdalin, a bitter chemical that converts into cyanide inside the human body. According to researchers, consuming wild almonds is fatal. A single gene mutation in wild almond trees resulted in a variety that no longer synthesizes amygdalin. When humans discovered this non- bitter almond species, they cultivated them, which is continued till today. Module IV  77 4. Murray Gray: a breed of beef cattle Murray gray is a cattle breed, obtained accidentally from the traditional cow species. The calves produced by the specific cow were more productive than those produced by the others. Farmers soon noticed the difference and started breeding from the offspring. This way, the Murray breed with some of the most positive characteristics has become popular all over Australia, which then spread to various other countries. 5. Wheat In wheat, genes of branched ears, lodging resistance, high protein and lysine, amber seed colour and awned spikelets were obtained and used in plant breeding. Among these is that for amber seed colour in wheat which enabled the cultivation or red seeded Mexican wheat varieties in India. A variety Sharbati Sonora resulted from this mutant and widely grown. 6. Rice In rice, one of the high yielding varieties Reimei was developed through mutations isolated after gamma irradiation. Mutants were also obtained in rice for increased protein and lysine content. In some mutants isolated in rice, duration of crop was reduced by as many as 60 days. Some of the japonica strains of rice which are yielding cannot be grown in India due to poor grain quality. Mutations in these ‘japonica’ strains could be induced to get indica type grains liked by Indian consumers, so that it will be possible now to grow these ‘japonica’ strains in India.  LEARNING ACTIVITY 1. What is the difference between chromosomal mutation and genetic mutation? (Use your own words to differentiate the two.) 2. How does mutation become beneficial? How does it become harmful? Elaborate your answer by giving concrete examples. Module IV