Textbook Assignment: Chapter 17, Pages 513 - 528
Major concepts .
Euploid variation in chromosome number: The term euploid refers to genomes that contain exact multiples of fully normal haploid sets of chromosomes (including one sex chromosome of either type per set). Diploid refers to a genome that has exactly two haploid sets of chromosomes. Polyploid refers to a genome that contains more than two haploid sets of chromosomes. Autopolyploid refers to a polyploid genome in which all of the haploid sets are from the same species. Allopolyploid refers to a polyploid genome that contains haploid genomes from two or more different species.
Aneuploid variation in chromosome number and morphology: The term aneuploid refers to all genomic variations that are not euploid, including increased or decreased numbers of individual chromosomes in an otherwise diploid background (monosomies and trisomies), as well as changes in chromosome morphology due to insertion, deletion, inversion and translocation, and changes in chromosome number due to centromeric fusion or fission. Cancer cells and permanent cell lines that are maintained in culture for extended periods of time often become grossly aneuploid. This lecture focuses on trisomy and polyploidy, with emphasis on plant systems, and also begins an examination of altered chromosomes. The next lecture finishes the examination of altered chromosomes and then examines aneuploidies of all types in humans.
Trisomies in plants: Trisomies (one extra copy of one of the chromosomes) are frequently viable in plants. In the case of Datura stramonium (Jimson weed), trisomies have been identified for all 12 of its chromosomes, each of which gives the seed capsule a characteristic appearance (Figure 9.10 in Klug and Cummings, Concepts of Genetiocs, 5th Ed., Norlin Reserve). Our textbook does not illustrate the Datura trisomies but describes studies with one of them in boxed example 17.1. The effect of trisomies on leaf shape in tomato plants are shown in figure 17.3. Such trisomies result in trivalent association of homologous chromosomes during meiosis, which in some cases can give rise to gametes containing a mixture of 1 and 2 copies of the trivalent chromosome, thus making it possible to perpetuate the trisomic condition. Example 17.1 examines patterns of inheritance in such a situation.
Even-numbered polyploids: Even numbered polyploids are potentially capable of normal meiotic pairing and thus are often fertile. In practice, allopolyploids are more likely to be fully fertile, since their chromosomes are derived from different species and thus are likely to contain minor differences that help to insure correct pairing during meiosis. Such chromosomes are sometimes referred to as homeologous, rather than homologous. Autopolyploids , which contain two diploid sets of chromosomes from the same species, often have reduced fertility due to aberrant pairing of multiple copies of identical chromosomes, but there are usually enough bivalents and tetravalents formed in autotetraploids to achieve some production of functional gametes.
Polyploidy in food plants: Polyploidy is common among plants, and often selected for in food plants because it increases cell size and thus the size of the fruit or seed grain that is produced. Thus, potatoes, coffee, peanuts, and McIntosh apples are tetraploid, bread wheat and barley are hexaploid, and strawberries are octaploid. Polyploidy also occurs in some types of animal life, but is not well tolerated systemically (in all body tissues) in most complex species. However, hepatocytes (liver cells) in humans and other mammals are generally polyploid. This is often referred to as endopolyploidy because it results from a process of "endomitosis" in which chromosomes are duplicated and separated but then merge into a single nucleus without cell division.
Origins of polyploidy: Polyploidy can occur naturally either through meiotic abnormalities that result in production of diploid gametes or through mitotic abnormalities that result in failure of mitosis to occur after the chromosomes have duplicated. Allotetraploidy is sometimes the result of mitotic duplication of chromosomes in a cross-species hybrid that would otherwise be sterile. The presence of two copies of all of the parental chromosomes from both species makes it possible for homologous (homeologous) pairing to occur, generating gametes that contain one copy of each of the chromosomes from both original parents. Because of this, allotetraploids are also sometimes referred to as amphidiploids.
Radish plus cabbage allopolyploid: A famous historical case is a cross between a radish and a cabbage done in the 1920's in Russia with the goal of producing a plant with the leaves of a cabbage and the root of a radish. . Each parent species had 18 chromosomes. The fertile plant that finally emerged after chromosome duplicaiton had 36 chromosomes. Unfortunately, it had the root of a cabbage and the leaves of a radish, and thus was of no agricultural value. Such a plant cannot breed successfully with either of the parents, and thus fully fits the definition of a new species!
Induced allopolyploidy: With modern technology, one does not have to wait for rare natural events to convert a sterile cross-species hybrid into a fertile allotertaploid. Instead, the process can be induced by drugs such as colchicine that disrupt mitotic spindle function and allow a single nuclear envelope to reform around the duplicated chromosomes. An example is the development in Canada of a cold-resistant allotetraploid for commercial production of rapeseed (Canola) oil. Two species with haploid chromosome numbers of 9 and 10 were used to generate an allotetraploid with a chromosome nubmer of 38.
Trictale: Another example of a man-made allopolyploid is trictale (figure 17.9), which was generated from a hexaploid wheat and a diploid rye. In this case, desirable properties of the rye and wheat parents were combined in the fertile hybrid. Trictale is not only considered to be a new species, but because of its differences from both of its parents, it has been assigned to a new genus.
Cell culture hybridization: Modern technology even makes it possible to generate fetile allopolyploids from plants that cannot be hybridized directly. Fusion of cultured cells from the two plants, followed by duplication of chromosome number and hormonal induction of differentiation can sometimes result in the formation of a fully fertile plant despite the incompatibility of cross-fertilization of the parental plants.
Sterile (seedless) odd numbered polyploids: Triploids (and other odd numbered polyploids) are sterile because they are unable to undergo meiotic pairing in a manner that will produce chromosomally balanced gametes. This property has been exploited to generate a number of types of seedless fruits, which are also generally larger than their diploid counterparts. Sterile autotriploids occur spontaneously when a meiotic failure results in a diploid gamete (which in most cases will combine with a normal haploid gamete). However, many commercial tirploids are produced by crossing a diploid of one species with a tetraploid of a slightly different species.
Bananas: Bananas are a classic example of a triploid seedless fruit. The little black dots in commercial bananas are abortive seeds that did not fully develop. A diploid banana is smaller and contains many large hard seeds about the size of coffee beans. Bananas have 22 chromosomes per haploid set. Each trivalent is expected to generate one haploid chromosome and one diploid pair. The chances that a gamete will be all haploid or all diploid is therefore (1/2)22. Thus, the chances of two euploid gametes participating in fertilization event that will lead to development of a seed is extremely small.
Other seedless triploids: Seedless watermelons are also triploids. It is relatively easy to produce large numbers of sterile triploids from a single plant for species that can be propagated vegetatively from cuttings. For those that cannot be grown in that manner, it is necessary to set up special crosses (such as diploid x tetraploid) to obtain seeds that will produce the sterile triploid plants. The process that is used to obtain seedless watermelons is described in a web page from Waynes Word, a web site that provides extensive plant information. The same site also has pages on seedless grapes and bananas.
Detection of altered chromosomes: The term heterokaryotipic is sometimes used (but not in our textbook) to describe individuals with homologous chromosomes that differ from each other. Such differences are most easily seen during pairing of homologous chromosomes, which occurs during meiotic prophase and also in certain types of somatic cells, such as the salivary glands of larval Drosophila. Sequences that are present in different orders on the two homologous chromosomes and sequences that are only present on one of them form a variety of loops and other convoluted structures as the homologous areas attempt to match up as closely as possible. Such structures can often be observed during meiotic prophase, although the small size and incomplete condensation of meiotic chromosomes may make detailed studies difficult.
Polytene chromosomes: The giant polytene chromosomes in the salivary glands of larval Drosophila are particularly well suited for observation of imperfectly matched pairing. Each chromosome has duplicated itself many hundred times, with all of the strands perfectly aligned, creating a structure that is readily visible with the light microscope even while the chromosomes remain relatively extended. In addition, the bound proteins and the folding of the DNA that does occur give the chromosomes a distinctive banded appearance (figure 10.19) that allows an expert to identify localized regions in great detail. Also, the two homologous chromosomes are paired, allowing loops and other forms of mispairing to be observed in much greater detail than is usually possible with meiotic chromosomes.
Deletions: A deletion is the absence of a chromosomal segment that is present in a wild type chromosome. Deletion of a segment at the end of a chromosome is called a terminal deletion. If both ends of the chromosome are in place and an internal segment is missing, the deletion is called an interstitial deletion. During meiotic or somatic pairing of homologs, deletions cause the formation of loops that consist of the portion of the normal chromosome that has nothing to pair with because of the deletion. Duplications cause very similar appearing loops, as described below.
Dominant lethal deletions: Deletions of moderate size often have dominant phenotypes that are lethal when they are homozygous (because of missing genes) . (Recall that this is how the dominant yellow lethal mutation in mice operates, as described in boxed example 13.2). Another example is the classic Notch deletion in Drosophila, which was originally detected as a dominant X-linked mutation that causes the posterior margins of the wings to be notched in heterozygous females. This deletion is presumed to be lethal in hemizygous males since they are never recovered. Thus, it can presumably also be viewed as a dominant lethal in homozygous females. However, actual detection of the lethality is not as simple as implied because there are no viable males to provide a second deleted X-chromosome in crosses with heterozygous females.
Partial hemizygosity: Deletions cause heterozygotes to be hemizygous for the deleted genes. This in turn results in the phenomenon sometimes called pseudodominance in which recessive alleles on the homologous normal chromosome are expressed in a hemizygous manner that superficially resembles dominance (figure 15.18).
No reversion of deletions: Another feature of deletion mutants is that they are non-reverting, since they reflect sequences that are totally absent and thus cannot be restored to functionality by a second mutation. Deletions that are large enough to span several genes are usually lethal when homozygous, and can cause pathology even when heterozygous due to gene dosage imbalances. A well known example is the human cri-du-chat (cry of cat) syndrome in newborn infants that are heterozygous for a deletion in the short arm of chromosome 5. We will examine this syndrome in the next lecture.
Duplications: Duplications of chromosomal material that occur on the original chromosome fall into three classes. Tandem duplications have extra copies of a chromosomal segment adjacent to the original and in the same orientation. Reverse duplications have an extra copy adjacent to the original, but in the opposite orientation. Duplications that are inserted into other parts of the original chromosome in either orientation are referred to as displaced duplications. Note that a duplication that is no longer on the original chromosome is called a translocation (discussed separately in the next lecture).
Duplication loops: During pairing of chromosomes that are heterozygous for a duplication, duplicated sequences that are unable to find a partner form a duplication loop. A very similar loop is seen when a deletion is present in one of the homologs. Duplications and deletions often occur concurrently, either as the result of breakage and rejoining of crossed chromosomes or as a consequence of unequal crossover (figure 17.13). Unequal crossing over is particularly likely to occur at the site of a pre-exisitng duplication, which facilitates achieving a good match at the point of crossover, even when the overall chromosomal alignment is distorted (figure 17.13)
Bar eye: The Bar eye mutation in Drosophila (figure 17.14)is a classic example of a duplication. The phenotypic effect of the Bar locus is to limit the number of facets in the eye. Wild type eyes have about 800 facets. The Bar mutation, which consists of a short duplication of the region contianing the Bar locus, reduces the number to about 70 in homozygous females (B/B) and in hemizygous males (B/Y), with about 350 in the heterozygoous female (B/+). Unequal crossing over within the Bar duplication can give rise to wild type gametes that contain only one copy of the Bar locus, and Double Bar (also called Ultrabar) gametes that contain three tandem repeats of it (figure 17.13). Double Bar (BD) reduces the number of eye facets to about 25 when homozygous or hemizygous.
Gene redundancy: It is important to recognize that not all duplications are abnormal. Many genes, such as those coding for the various ribosomal RNAs, are highly repeated in the normal genomes of most species, often in the form of tandem repeats. In addition, the genomes of higher organisms contain substantial amounts of other repetitive DNA, including some sequences with very high levels of repetition that are species specific and do not have any known genetic function.
Evolutionary role of gene duplication: There is substantial evidence that gene duplication has played a major role in the evolution of higher organisms. Complex genomes, such as those of humans, contain large families of closely related genes with slightly different funcitons that appear to have arisen through duplication followed by divergence of function, with one copy maintaining the original funciton while others have become modified in ways that have allowed them to acquire new functions.
Inversions: Reversal of the sequence of genes on a segment of a chromosome is called an inversion. Inversions that do not include the centromere are called paracentric, whereas those that do include the centromere are called pericentric. Inversions cause the formation of chromosomal loops in which one of the strands is crossed (figure 17.16). When crossing over occurs within an inversion loop, a variety of chromosomal abnormalities can be generated (figure 17.17).
Dicentric and acentric chromosomes: Crossing over in a paracentric inversion loop can result in the formation of a chromosomes with two centromeres that will form a dicentric bridge during anaphase I of meiosis. The reciprocal crossover products will be acentric chromosomes that do not contain centromeres and are thus lost during anaphase.
Duplications and deletions: A variety of duplications and deletions are generated when crossing over occurs in pericentric inversions. Note that the dicentric and acentric chromosomes generated by crossing over in paracentric loops can also be viewed as duplications and deletions that include the centromere.
Evolutionary consequences: Crossing over within inversion loops generates non-functional chromosomes and thus reduces the number of fertile gametes produced by inversion heterozygotes. However, in certain cases rendering the products of crossing over infertile when hybridized with non-crossover strains appears to keep specific combinations of alleles together in ways that can provide a selective advantage to the crossover strain. The evidence for this is the maintenance of inversions in certain wild populations, such as Drosophila pseudoobscura. This can aslo be an early step toward reproductive isolation of a new species.