MUTATION BOT-704 (RADIATION & MOLECULAR BIOLOGY) (DEPARTMENT OF BOTANY, UAF) MUTATION • An alteration in the genetic material (the genome) of a cell of a living organism or of a virus that is more or less permanent and that can be transmitted to the cell’s or the virus’s descendants. • The genomes of organisms are all composed of DNA, whereas viral genomes can be of DNA or RNA. • A mutated form of a gene is called a mutant allele TYPES (ON BASIS OF CELLS) 1-SOMATIC MUTATION • Mutation in the DNA of a body cell of a multicellular organism may be transmitted to descendant cells by DNA replication and hence result in a sector or patch of cells having abnormal function. • An example being cancer. TYPES (ON BASIS OF CELLS) 2-GERMINAL MUTATION • Mutations in egg or sperm cells may result in an individual offspring all of whose cells carry the mutation, which often confers some serious malfunction, • As in the case of a human genetic disease such as cystic fibrosis. • Cystic fibrosis (CF) is an inherited disorder that causes severe damage to the lungs, digestive system and other organs in the body. CAUSES • Mutations result either from accidents during the normal chemical transactions of DNA, often during replication, or • from exposure to high-energy electromagnetic radiation (e.g., ultraviolet light or X-rays) or • particle radiation or to highly reactive chemicals in the environment. EFFECT OF MUTATION • Because mutations are random changes, they are expected to be mostly deleterious, but some may be beneficial in certain environments. • In general, mutation is the main source of genetic variation, which is the raw material for evolution by natural selection. • The genome is composed of one to several long molecules of DNA, and mutation can occur potentially anywhere on these molecules at any time. • The most serious changes take place in the functional units of DNA, the genes. TYPES OF MUTATIONS 1-SILENT MUTATIONS • many mutations are silent, showing no obvious effect at the functional level. • Some silent mutations are in the DNA between genes, or they are of a type that results in no significant amino acid changes and thus protein will be functional. • Because of this, the changes are regarded as though they are evolutionarily neutral. TYPES OF MUTATIONS • For example, if the codon AAA is altered to become AAG, the same amino acid – lysine – will be incorporated into the peptide chain. 2-POINT MUTATIONS • Changes within genes are called point mutations. • Kinds of Point Mutations: • The simplest kinds are changes to single base pairs, called base-pair substitutions. • Many of these substitute an incorrect amino acid in the corresponding position in the encoded TYPES OF MUTATIONS protein, and of these a large proportion result in altered protein function. • Some base-pair substitutions produce a stop codon. • Normally, when a stop codon occurs at the end of a gene, it stops protein synthesis, but, when it occurs in an abnormal position, it can result in a truncated and nonfunctional protein. • Another type of simple change, the deletion or insertion of single base pairs, generally has a profound effect on the protein because the protein’s synthesis, which is carried out by the reading of triplet codons in TYPES OF MUTATIONS a linear fashion from one end of the gene to the other, is thrown off. • This change leads to a frameshift in reading the gene such that all amino acids are incorrect from the mutation onward. • More-complex combinations of base substitutions, insertions, and deletions can also be observed in some mutant genes. • For example, sickle-cell disease is caused by a single point mutation in the betahemoglobin TYPES OF MUTATIONS gene that converts a GAG codon into GUG, which encodes the amino acid valine rather than glutamic acid at carbon no 6. 3-CHROMOSOMAL MUTATIONS • Mutations that span more than one gene are called chromosomal mutations because they affect the structure, function, and inheritance of whole DNA molecules. • Often these chromosome mutations result from one or more coincident breaks in the DNA TYPES OF MUTATIONS molecules of the genome (possibly from exposure to energetic radiation), followed in some cases by faulty rejoining. • Some outcomes are large-scale deletions, duplications, inversions, and translocations. • In a diploid species (a species, such as human beings, that has a double set of chromosomes in the nucleus of each cell), deletions and TYPES OF MUTATIONS duplications alter gene balance and often result in abnormality. • Inversions and translocations involve no loss or gain and are functionally normal unless a break occurs within a gene. • However, at meiosis, faulty pairing of an inverted or translocated chromosome set with TYPES OF MUTATIONS a normal set can result in gametes and hence progeny with duplications and deletions. • Another type of chromosome mutation is the gain or loss of whole chromosome sets. • Loss of whole chromosomes results in a condition called aneuploidy. • Gain of sets results in polyploidy—that is, the presence of three, four, or more chromosome sets instead of the usual two. TYPES OF MUTATIONS • Polyploidy has been a significant force in the evolution of new species of plants and animals. MOBILE DNA ELEMENTS • Most genomes contain mobile DNA elements that move from one location to another. • The movement of these elements can cause mutation, either because the element arrives in some crucial location, such as within a gene, or because it promotes large-scale chromosome mutations via recombination between pairs of mobile elements in different locations. MUTATIONAL PRESSURE • Most are eliminated by chance. • In some cases a mutant allele can increase in frequency by chance, and then individuals expressing the allele can be subject to selection, either positive or negative. • Hence, for any one gene the frequency of a mutant allele in a population is determined by a combination of mutational pressure, selection, and chance. GENE MUTAION • Need of Gene Mutation Study • 1. Variants in genes (which are caused by mutations) are needed to study the transmission of traits • 2. Mutations can tell the researcher about the function of a gene product in a biological system • 3. Mutations are the basis for cancer and other genetic diseases • 4. Gene mutations serve as the source for most alleles in a population and is therefore the origin of genetic variation within a population • 5. Mutations drive evolution: mutations are the raw material upon which natural selection acts. MEASURING MUATION Frequencies of mutations • Mutation frequency = # of times mutation appears in the population / # of individuals in the population where a population can be bacterial cells, people, gametes • Mutation rate = # of mutations / unit time where unit time can be per cell division, cell generation MUTATION & CANCER • A. Cancer is a group of diseases characterized by rapid, uncontrolled proliferation of cells within a tissue resulting in the formation of a tumor. • Cancer has many causes and phenotypes but the fundamental mechanism underlying all cancers is genetic. • B. There are two types of genes that are involved in cancer formation. • 1. Tumor suppressor genes are genes that encode a product that normally stops cell division. • Mutations in these genes result in uncontrolled activation of cell division and therefore tumor formation. MUTATION & CANCER • Mutations are generally recessive and thus you need mutations in both alleles to have cancer. • A mutation in one allele predisposes the carrier to cancer. • a) Rb gene - retinoblastoma (retinal cancer) • b) BRCA1 - hereditary breast cancer gene • c) p53 gene mutations are found in a variety of cancers including breast, lung, bladder, MUTATION & CANCER and colon cancers. Over 1/2 of all cancers are associated with p53. • 2. Proto-oncogenes are genes that encode a product that normally controls cell division (kind of like an on/off switch). • Mutations in these genes make the gene product permanently in the on position which results in uncontrolled activation of cell division and therefore tumor formation. MUTATION & CANCER • a) N-ras – neuroblastoma (tumor formed of embryonic ganglion cells), leukemia • b) N-myc – neuroblastoma • c) man – mammary carcinoma THANKS !
