11.6: DNA Mutation

Describe the types of mutations that can affect genes. Explain what can cause a mutation.

A sickle ….

Sickle Cell Disease

Sickle cell disease is an example of a disorder caused by a genetic mutation. In sickle cell disease, the hemoglobin in red blood cells tends to bind together when oxygen levels are low. The hemoglobin crystals deform the red blood cells into sickle, or crescent, shapes.

The sickle-shaped cells clog tiny blood vessels, dangerously blocking the normal flow of blood.Blood capillaries burst…other painful symptoms result…

The molecular basis for the disease lies in the difference of only one DNA nucleotide out of a 438-base sequence.

Sickle cell protein

How Mutations Affect Genes

A mutation is any change in the nucleotide sequence of DNA. Mutations can involve large regions of a chromosome or just a single nucleotide pair, as in the sickle cell allele described previously. How can small changes such as altering a single nucleotide in the DNA sequence cause such big changes in the phenotype?

Mutations within a gene can be divided into 2 general categories:

1. Base substitutions 2. Base insertions or deletions.

A base substitution is the replacement of one base or nucleotide with another. Occasionally, a base substitution causes no change to a protein, but sometimes it results in a change that affects the function of a protein, sometimes drastically (as in the base substitution leading to sickle cell disease). Mutation that does not cause a change in protein structure is called a "silent mutation." Other changes of a single nucleotide may result in an mRNA that codes for an amino acid whose chemical properties are similar enough to the original amino acid that there is little effect on the overall function of the protein.

Base Insertion or Deletion MutationInsertion or deletion of one or more nucleotides in a gene is usually more disastrous than the effects of a base substitution. Because mRNA is read as a series of triplets, adding or subtracting nucleotides may alter the triplet groupings of the genetic message. Therefore, all the nucleotides that are "downstream" of the mutation will be regrouped into different codons. These new codons code for new amino acids. The result will be a different, and probably nonworking, protein.

What Causes Mutations?

Mutations may occur when errors are made during DNA replication, or when errors are made during chromosome crossovers in meiosis.

What Causes Mutations?

Physical or chemical agents that cause mutations are called mutagens . The

most common physical mutagen is high-energy radiation, such as X-rays and ultraviolet light.

What Causes Mutations?

One type of chemical mutagen consists of chemicals that are similar to normal DNA bases but cause incorrect base-pairing when incorporated into DNA.

Most Mutations are Deadly!

Mutations happen. They happen with great regularity. Almost all mutations are lethal……to the individual. Especially is it involves a “frameshift”.Remember that an insertion or deletion causes the frame shift. A silent mutation is not lethal because it is a point mutation and it does not change the amino acid that is coded for.

Some rare mutations may not be harmful!

Although mutations are often harmful, they can alter a protein in a way that may be beneficial in certain environments. For example, a genetic mutation is responsible for the dark color seen in some females of the tiger swallowtail butterfly species, Papilio glaucus. The mutation may be advantageous when the environment includes a related species, the poisonous black swallowtail Battus philenor. Predators that avoid eating the black swallowtail may also avoid eating its mimic, the dark form of P. glaucus.Papilio glaucus fitness is thus increased!

Helpful Mutations: Fitness

Battus philenor

(Bitter-tasting)

Papilio glaucus

Normal female

Papilio glaucus

Mutant female

If a mutation is present in an organism's gametes, it can be passed on to its offspring. According evolution theory, mutations are the “engine” for the genetic diversity in the living organisms.

30 New Mutations per Lifetime

As scientists learn to read the instructions in our genes, they are discovering that much of our DNA is riddled with errors. Fortunately, most of these errors are harmless. Considering the difficulties involved—the 6 feet of DNA in a human cell consists of 6 billion subunits, or base pairs, coiled and tightly packed into 23 pairs of chromosomes, all of which must be duplicated every time a cell divides—our general state of health is something of a miracle. We each inherit hundreds of genetic mutations from our parents, as they did from their forebears. In addition, the DNA in our own cells undergoes an estimated 30 new mutations during our lifetime, either through mistakes during DNA copying or cell division or, more often, because of damage from the environment. Bits of our DNA may be deleted, inserted, broken, or substituted. Most mutations affect only the parts of DNA that do not contain instructions for making a gene, so we need not worry about them. Problems arise only when an error in DNA alters a message that tells certain cells to manufacture a certain protein. Such messages are spelled out in varying sequences of the four chemical bases that make up DNA: adenine (A), thymine (T), guanine (G), and cytosine (C). To stay alive and functioning, the human body requires a daily crop of billions of fresh protein molecules—about 40,000 different kinds of proteins that must be supplied in the right quantities, at the right times, and in the right places. We need hemoglobin to carry oxygen through the bloodstream, antibodies to fight foreign substances, hormones to deal with stress, neurotransmitters to evoke movements, emotions, and thought, and many other proteins to give structure to organs or speed up chemical reactions.