1. Discuss the three different types of gene mutations discussed in the commentary: Week 6–Gene Mutations and DNA Repair. Describein detail how insertion, deletion, and base substitution of nucleotides can have a significant impact on genes. Find three specific examples (actual genemutations, not chromosome mutations) of ways in which a very small change in DNA can have a major impact on an organism, and describe each mutation in detail.
2. Why do agricultural researchers intentionally produce polyploid crop plants? Explain in detail what polyploidy means and discuss different types of polyploid plants. Give four specific detailed examples of actual commercial crops that are polyploid. In each case explain why polyploidy is advantageous. Also, indicate whether the polyploidy occurred naturally or describe how botanists created the new varieties. Why is it more common for polyploidy to occur in plants than in animals? Give examples of types of animals that have been found to exhibit polyploidy.

Information needed to answer these questions.

Mutations

Antoine LeBlanc, one of 18 white alligators known to exist in the world.The eight-year -old, six-foot-long, 50-lb. reptile is white as a result of a genetic mutation called leucism. (AP Photo/Robin Weiner)

Mutations are often called the "raw material of evolution." Evolution means change through time, and in terms of genetics, evolution means a change in the frequency of alleles in the gene pool of a population. Evolution by means of natural selection relies on survival of the fittest among a population of organisms that show phenotypic variety in their genetic traits. Genetic variety may be increased through immigration of new individuals. The ultimate source of genetic variety, however, is mutations.

A mutation is an alteration in the structure of a gene or chromosome. It may involve duplications, deletions, or rearrangements of DNA. Mutations may be so small that they affect single base pairs of the DNA, or large enough to affect entire chromosomes. As you might expect, the vast majority of mutations are harmful, or even lethal.

Occasionally, however, a mutation has a beneficial effect on the phenotype of an individual, which confers an evolutionary advantage over the other members of the population. If the individual gains a reproductive advantage over other members of the species, the frequency of occurrence of the mutation may increase rapidly in the population.

Mutations that involve whole chromosomes or large portions of chromosomes are termed chromosomal mutations. Examples of chromosomal mutations include abnormal numbers of chromosomes, deletions or duplications of parts of chromosomes, and rearrangements of large segments of DNA, such as inversions that reverse the order of a series of genes, and translocation of genes to new locations. Smaller mutations that occur on the level of individual genes are termed gene mutations. Gene mutations involve the addition, deletion, or substitution of one or more nucleotides in a gene.

Over the past few decades, scientists have been intrigued by the fact that there is a great deal of duplication in DNA. The discovery of sequences that are repeated over and over along the DNA led to a variety of hypotheses as to the reason for all this redundancy. Sometimes referred to as genetic "junk," these normally untranscribed segments are now thought of as possibly important to the development of new genes in the course of evolution. If a product of a gene is crucial to the survival of the organism, it stands to reason that most mutations in that gene would be lethal. If, however, there are multiple copies of the gene, then a mutation in one of the copies will probably not adversely affect the individual. Multiple copies of genes allow for a lot more chance for modification without harm. A beneficial mutation, such as instructions for a slightly different respiratory pigment, may confer an evolutionary advantage to the individuals expressing it, and it may become an important new gene in the gene pool of the population.

Abnormalities in Chromosome Number

All organisms have a set number of chromosomes in their genome. Cells with one set of chromosomes are termed haploid. In humans, only the gametes have a haploid number of chromosomes (23 chromosomes). Cells with two sets of chromosomes are termed diploid. In humans, all other cells (somatic cells) are diploid, because they have two sets of 23 chromosomes, for a total of 46 chromosomes. Some types of chromosomal mutations involve abnormalities in chromosome number. Loss of a chromosome is usually lethal, but some organisms can tolerate extra copies of chromosomes, especially plants.

Aneuploidy refers to the condition of having an abnormal number of chromosomes, other than the gain of entire sets of chromosomes, which is termed polyploidy. The gain or loss of one chromosome is the most common form of aneuploidy. This chromosomal mutation results from nondisjunction, which is failure of homologous chromosomes to separate during meiosis.

Nondisjunction can occur during the first or second meiotic division, as seen in the diagram (below).

Nondisjunction results in aneuploid gametes, which may join normal haploid gametes to produce monosomic or trisomic zygotes. Monosomy, in which one chromosome is missing, is usually a lethal condition, even though the homolgous chromosome is present, with one copy of each gene. One theory that would explain this phenomenon suggests that the presence of recessive lethal alleles that are not masked by dominant normal, wild-type, alleles cause the death of the individual. Turner syndrome (45,X) is the only non-lethal type of monosomy in humans. Cri-du-chat syndrome results from the loss of a small part of chromosome 5.

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Trisomy results from the addition of an extra chromosome following nondisjunction. The only common example of trisomy in humans is Down syndrome (47,21+), sometimes called trisomy 21. In 95% of Down syndrome cases, the extra chromosome 21 is caused by nondisjunction, and does not run in families. The mistake in meiosis almost always occurs in the formation of the ovum, and is thought to result from the advanced age of oocytes that began their development before the mother's birth. Familial Down syndrome is responsible for the other 5% of cases, and has a completely different cause, unrelated to the age of the mother: translocation of chromosome 21. This syndrome does run in families, and is discussed in the next commentary.

View the following animation about nondisjunction.

Polyploidy is a condition in which there are more than two sets of chromosomes in cells. Triploidy (3n) can result when an entire set of chromosomes fails to disjoin during meiosis, and the resulting diploid gamete joins with a normal haploid gamete to form a triploid zygote. Triploidy can also result from an ovum that is fertilized by two sperm cells. Tetraploidy (4n) can result from cells that replicate their chromosomes, but reenter interphase instead of dividing. Researchers can induce the formation of polyploid organisms by using colchicine, which disrupts the formation of the spindle apparatus, thereby preventing segregation of the chromosomes. Polyploidy is infrequent among animals, but more common among plants. Tetraploid cells, with an even number of sets of chromosomes, can undergo normal meiosis, with twice as many homologous pairs of chromosomes.

Chromosomal Mutations

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Chromosomal mutations that involve structural changes in chromosomes include deletion, duplication, inversion, and translocation. These mutations are caused by breaks in chromosomes, followed by an alteration of the gene sequence. Broken chromosomes have "sticky" ends that may join with the "sticky" ends of the same chromosome or other broken chromosomes.

View an animation on the different types of mutations.

The origin of duplicated and deficient regions of chromosomes as a result of unequal crossing over. The tetrad on the left is mispaired during synapsis. A single crossover between chromatids 2 and 3 results in the deficient (chromosome 2) and duplicated (chromosome 3) chromosomal regions shown on the right. The two chromosomes uninvolved in the crossover event remain normal in gene sequence and content.

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Inversion results in the flipping over and reinsertion of a segment of the chromosome, so that the affected genes are in backwards order. Individuals with inversions may be normal, but their gametes may be abnormal.

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Translocation involves the movement of part of a chromosome to a new location. In the following illustration of familial Down syndrome, short ends of chromosomes 14 and 21 have broken off and are lost (fortunately none of the lost genes are necessary for survival). The two "sticky" ends attach to form a large chromosome that is a combination of the two chromosomes. An individual with this transformation has a normal phenotype. During gamete formation, however, the three chromosomes can produce four different types of gametes: one normal, one lethal, one carrier, and one that displays trisomy 21--the familial type of Down syndrome, which represent 5% of all cases. As discussed in the commentary, "Abnormalities in Chromosome Number," 95% of Down syndrome cases are caused by nondisjunction.

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Deletion involves the loss of a part of a chromosome. A terminal deletion results in the loss of the entire end of a chromosome, such as in cri-du-chat syndrome. An intercalary deletion occurs in the interior of the chromosome, and requires two breaks in the chromosome. Look at the formation of a deficiency loop in the diagram, which illustrates how a chromosome with an intercalary deletion can synapse successfully during synapsis.

View an animation about deletions.

Duplication can result from a mistake during replication of the chromosome, or from unequal crossing over during synapsis, as in the diagram. As discussed in the "Mutations" commentary, duplication may be very important in providing extra copies of genes, in which mutations may occur without having lethal implications for the organism.

Gene Mutations and DNA Repair

Gene mutations involve changes in much smaller sections of DNA than chromosomal mutations, usually affecting only a single gene, often affecting only one nucleotide pair. There are three basic types of gene mutations: base substitutions (also called point mutations) are potentially the least harmful since they do not cause a frameshift mutation, the way that a deletion or an insertion does. The example on this page demonstrates the damage caused by frameshift mutations, using sentences to represent genes, and letters to represent nucleotides.

(above) Analogy of the impact of the substitution, deletion, and insertion of one letter in a sentence composed of three-letter words demonstrating point and frameshift mutations.

A mutagen is something that causes a mutation, such as radiation and some types of chemicals.

Any type of radiation that contains more energy than visible light can cause mutations. Ultraviolet (UV) light, X-rays, gamma rays and cosmic rays are all mutagenic. UV light can cause mutations in DNA, as shown in the following animation which illustrates the formation of dimers (unusual attachments) along the DNA.

Researchers discovered that in E. coli the damage caused by UV light could be repaired by an enzyme in a process called photoreactivation repair, demonstrated in the following animation.

The replication (duplication) of DNA is extremely accurate, but not perfect. Mistakes occur in approximately one out of every 100,000 nucleotide insertions. DNA polymerase (the enzyme responsible for enabling the insertion of complementary nucleotides in the new DNA strand being created along the old template strand of DNA) occasionally inserts an incorrect nucleotide. Fortunately, DNA polymerase proofreads its work and corrects 99% of its errors, by backing up, cutting out the incorrect nucleotide, and replacing it with a correct nucleotide. Those few errors that escape correction, along with many of the gene mutations discussed above, are sometimes detected and repaired by several different protein complexes involved in DNA repair.

Mismatch repair involves finding a spot on the DNA where the nucleotides are mismatched (the bases are not complementary). It is important to determine which strand is the new incorrect strand by the absence of methyl groups (newly formed DNA strands are not yet methylated--later they will have methyl groups attached to them; these methyl groups will be important to the structure of chromosomes). The incorrect nucleotide is then excised and replaced by a correct necleotide.

Post-replication repair is responsible for repairing damage to DNA, perhaps caused by one of the mutagens described above. The following animation demonstrates how correct nucleotides from the original parent strand are used to correct the gap caused by the mutation in the newly replicated strand. Subsequently, the missing nucleotides in the parental strand are replaced.

It is important to determine what substances may be mutagenic to humans. Bruce Ames developed a test in the 1970s that is still used by chemical and pharmaceutical companies to assess the mutagenic potential of chemical products. The Ames test is described in the following animation.