Chromosome Mutations: Variation in Number and Arrangement PDF

6 Chromosome Mutations: Variation in Number and Arrangement CHAPTER CONCEPTS Spectral karyotyping of human chromosomes utilizing The failure of chromosomes to prop- differentially la...

6 Chromosome Mutations: Variation in Number and Arrangement CHAPTER CONCEPTS Spectral karyotyping of human chromosomes utilizing The failure of chromosomes to prop- differentially labeled “painting” probes. erly separate during meiosis results in variation in the chromosome content of gametes and subsequently in offspring I arising from such gametes. n previous chapters, we have emphasized how mutations and the result- Plants often tolerate an abnormal ing alleles affect an organism’s phenotype and how traits are passed from genetic content, but, as a result, they parents to offspring according to Mendelian principles. In this chapter, we often manifest unique phenotypes. look at phenotypic variation that results from more substantial changes than Such genetic variation has been an alterations of individual genes—modifications at the level of the chromosome. important factor in the evolution of Although most members of diploid species normally contain precisely plants. two haploid chromosome sets, many known cases vary from this pattern. In animals, genetic information is in a Modifications include a change in the total number of chromosomes, the delicate equilibrium whereby the gain deletion or duplication of genes or segments of a chromosome, and rearrange- or loss of a chromosome, or part of a ments of the genetic material either within or among chromosomes. Taken chromosome, in an otherwise diploid together, such changes are called chromosome mutations or chromosome organism often leads to lethality or to aberrations in order to distinguish them from gene mutations. Because the an abnormal phenotype. chromosome is the unit of genetic transmission, according to Mendelian The rearrangement of genetic informa- laws, chromosome aberrations are passed to offspring in a predictable man- tion within the genome of a diploid ner, resulting in many unique genetic outcomes. organism may be tolerated by that Because the genetic component of an organism is delicately balanced, organism but may affect the viability of even minor alterations of either content or location of genetic information gametes and the phenotypes of organ- isms arising from those gametes. within the genome can result in some form of phenotypic variation. More Chromosomes in humans contain substantial changes may be lethal, particularly in animals. Throughout this chapter, we consider many types of chromosomal aberrations, the pheno- fragile sites—regions susceptible to breakage, which lead to abnormal typic consequences for the organism that harbors an aberration, and the phenotypes. impact of the aberration on the offspring of an affected individual. We will also discuss the role of chromosome aberrations in the evolutionary process. 99 100 6 CHROMOSOME MUTATIONS: VARIATION IN NUMBER AND ARRANGEMENT TABLE 6.1 Terminology for Variation in Chromosome Numbers 6.1 Variation in Chromosome Term Explanation Number: Terminology and Origin Aneuploidy 2n { x chromosomes Monosomy 2n - 1 Variation in chromosome number ranges from the addi- Disomy 2n tion or loss of one or more chromosomes to the addition Trisomy 2n + 1 of one or more haploid sets of chromosomes. Before we Tetrasomy, pentasomy, etc. 2n + 2, 2n + 3, etc. embark on our discussion, it is useful to clarify the termi- Euploidy Multiples of n nology that describes such changes. In the general condi- tion known as aneuploidy, an organism gains or loses one Diploidy 2n or more chromosomes but not a complete set. The loss of Polyploidy 3n, 4n, 5n,!.!.!.! a single chromosome from an otherwise diploid genome is Triploidy 3n called monosomy. The gain of one chromosome results in Tetraploidy, pentaploidy, etc. 4n, 5n, etc. trisomy. These changes are contrasted with the condition Autopolyploidy Multiples of the same genome of euploidy, where complete haploid sets of chromosomes Allopolyploidy Multiples of closely related are present. If more than two sets are present, the term (amphidiploidy) genomes polyploidy applies. Organisms with three sets are specifi- cally triploid, those with four sets are tetraploid, and so on. Klinefelter syndrome or Turner syndrome, respectively Table 6.1 provides an organizational framework for you to (see Figure 5.2). Human females may contain extra X chro- follow as we discuss each of these categories of aneuploid mosomes (e.g., 47,XXX, 48,XXXX), and some males contain and euploid variation and the subsets within them. an extra Y chromosome (47,XYY). As we consider cases that include the gain or loss of Such chromosomal variation originates as a random chromosomes, it is useful to examine how such aberrations error during the production of gametes, a phenomenon originate. For instance, how do the syndromes arise where referred to as nondisjunction, whereby paired homologs fail the number of sex-determining chromosomes in humans is to disjoin during segregation. This process disrupts the nor- altered, as described in Chapter 5? As you may recall, the mal distribution of chromosomes into gametes. The results gain (47,XXY) or loss (45,X) of an X chromosome from an of nondisjunction during meiosis I and meiosis II for a single otherwise diploid genome affects the phenotype, resulting in chromosome of a diploid organism are shown in Figure 6.1. First-division Normal nondisjunction disjunction First meiotic division Normal Normal Second-division disjunction Second meiotic disjunction nondisjunction division Gametes Haploid Trisomic Trisomic Monosomic Monosomic Haploid Disomic Disomic Trisomic Monosomic gamete gamete (normal) (normal) F I G U R E 6. 1 Nondisjunction during the first and second meiotic divisions. In both cases, some of the gametes that are formed either contain two members of a specific chromosome or lack that chromosome. After fertilization by a gamete with normal haploid content, monosomic, disomic (normal), or trisomic zygotes are produced.  6.2 MONOSOMY AND TRISOMY RESULT IN A VARIETY OF PHENOTYPIC EFFECTS 101 As you can see, abnormal gametes can form that contain explanation is that if just one of those genes is represented either two members of the affected chromosome or none at by a lethal allele, monosomy unmasks the recessive lethal all. Fertilizing these with a normal haploid gamete produces allele that is tolerated in heterozygotes carrying the cor- a zygote with either three members (trisomy) or only one responding wild-type allele, leading to the death of the member (monosomy) of this chromosome. Nondisjunction organism. In other cases, a single copy of a recessive gene leads to a variety of aneuploid conditions in humans and due to monosomy may be insufficient to provide life- other organisms. sustaining function for the organism, a phenomenon called haploinsufficiency. N O W S O LV E T H I S Aneuploidy is better tolerated in the plant kingdom. Monosomy for autosomal chromosomes has been observed 6.1 A human female with Turner syndrome (45,X) also in maize, tobacco, the evening primrose (Oenothera), and expresses the X-linked trait hemophilia, as did her father. the jimson weed (Datura), among many other plants. Nev- Which of her parents underwent nondisjunction during mei- osis, giving rise to the gamete responsible for the syndrome? ertheless, such monosomic plants are usually less viable than their diploid derivatives. Haploid pollen grains, which HINT: This problem involves an understanding of how nondis- undergo extensive development before participating in fer- junction leads to aneuploidy. The key to its solution is first to tilization, are particularly sensitive to the lack of one chro- review Turner syndrome, discussed above and in more detail in Chapter 5, then to factor in that she expresses hemophilia, and mosome and are seldom viable. finally, to consider which parent contributed a gamete with an X chromosome that underwent normal meiosis. Trisomy In general, the effects of trisomy (2n + 1) parallel those of ES SENT IA L P OINT monosomy. However, the addition of an extra chromosome Alterations of the precise diploid content of chromosomes produces somewhat more viable individuals in both animal are referred to as chromosomal aberrations or chromosomal and plant species than does the loss of a chromosome. In mutations. animals, this is often true, provided that the chromosome involved is relatively small. However, the addition of a large autosome to the diploid complement in both Drosophila 6.2 Monosomy and Trisomy Result and humans has severe effects and is usually lethal during development. in a Variety of Phenotypic Effects In plants, trisomic individuals are viable, but their phenotype may be altered. A classical example involves the We turn now to a consideration of variations in the number jimson weed, Datura, whose diploid number is 24. Twelve of autosomes and the genetic consequence of such changes. primary trisomic conditions are possible, and examples of The most common examples of aneuploidy, where an organ- each one have been recovered. Each trisomy alters the phe- ism has a chromosome number other than an exact multiple notype of the plant’s capsule sufficiently to produce a unique of the haploid set, are cases in which a single chromosome is phenotype. These capsule phenotypes were first thought to either added to, or lost from, a normal diploid set. be caused by mutations in one or more genes. Still another example is seen in the rice plant (Oryza sativa), which has a haploid number of 12. Trisomic strains Monosomy for each chromosome have been isolated and studied— The loss of one chromosome produces a 2n - 1 complement the plants of 11 strains can be distinguished from one called monosomy. Although monosomy for the X chromo- another and from wild-type plants. Trisomics for the longer some occurs in humans, as we have seen in 45,X Turner syn- chromosomes are the most distinctive, and the plants grow drome, monosomy for any of the autosomes is not usually more slowly. This is in keeping with the belief that larger tolerated in humans or other animals. In Drosophila, flies that chromosomes cause greater genetic imbalance than smaller are monosomic for the very small chromosome IV (contain- ones. Leaf structure, foliage, stems, grain morphology, and ing less than 5 percent of the organism’s genes) develop more plant height also vary among the various trisomies. slowly, exhibit reduced body size, and have impaired viabil- ity. Monosomy for the larger chromosomes II and III is appar- ently lethal because such flies have never been recovered. Down Syndrome: Trisomy 21 The failure of monosomic individuals to survive is at The only human autosomal trisomy in which a significant first quite puzzling, since at least a single copy of every number of individuals survive longer than a year past gene is present in the remaining homolog. However, one birth was discovered in 1866 by John Langdon Down. The  102 6 CHROMOSOME MUTATIONS: VARIATION IN NUMBER AND ARRANGEMENT © Design Pics/Alamy F I G U R E 6. 2 The karyotype and a photograph of a child with Down syndrome (hugging her unaffected sister on the right). In the karyotype, three members of the G-group chromosome 21 are present, creating the 47, 21 + condition. condition is now known to result from trisomy of chromo- to an average of about 50 years, individuals are known to some 21, one of the G group* (Figure 6.2), and is called survive into their 60s. Down syndrome or simply trisomy 21 (designated! 47, ! Children with Down syndrome are prone to respiratory 21+ ). This trisomy is found in approximately 1 infant in disease and heart malformations, and they show an inci- every 800 live births. While this might seem to be a rare, dence of leukemia approximately 20 times higher than that improbable event, there are approximately 4000–5000 such of the normal population. However, careful medical scru- births annually in the United States, and there are currently tiny and treatment throughout their lives can extend their over 250,000 individuals with Down syndrome. survival significantly. A striking observation is that death Typical of other conditions classified as syndromes, in older adults with Down syndrome is frequently due to many phenotypic characteristics may be present in trisomy Alzheimer disease. The onset of this disease occurs at a much 21, but any single affected individual usually exhibits only earlier age than in the normal population. a subset of these. In the case of Down syndrome, there are Because Down syndrome is common in our population, 12 to 14 such characteristics, with each individual, on aver- a comprehensive understanding of the underlying genetic age, expressing 6 to 8 of them. Nevertheless, the outward basis has long been a research goal. Investigations have appearance of these individuals is very similar, and they given rise to the idea that a critical region of chromosome bear a striking resemblance to one another. This is, for the 21 contains the genes that are dosage sensitive in this tri- most part, due to a prominent epicanthic fold in each eye** somy and responsible for the many phenotypes associated and the typically flat face and round head. People with Down with the syndrome. This hypothetical portion of the chromo- syndrome are also characteristically short and may have a some has been called the Down syndrome critical region protruding, furrowed tongue (which causes the mouth to (DSCR). A mouse model was created in 2004 that is trisomic remain partially open) and short, broad hands with charac- for the DSCR, although some mice do not exhibit the char- teristic palm and fingerprint patterns. Physical, psychomo- acteristics of the syndrome. Nevertheless, this remains an tor, and cognitive!disabilities are evident, and poor muscle important investigative approach. tone is characteristic. While life expectancy is shortened Current studies of the DSCR region in both humans and mice have led to several interesting findings. We now believe that the three copies of the genes present in this region are!necessary, but themselves not sufficient, for the cogni- *On the basis of size and centromere placement, human autosomal tive deficiencies characteristic of the syndrome. Another chromosomes are divided into seven groups: A (1–3), B (4–5), C (6–12), D (13–15), E (16–18), F (19–20), and G (21–22). finding involves the important observation that Down syn- drome individuals have a decreased risk of developing a !**The epicanthic fold, or epicanthus, is a skin fold of the upper eyelid, extending from the nose to the inner side of the eyebrow. It number of cancers involving solid tumors, including lung covers and appears to lower the inner corner of the eye, giving the cancer and melanoma. This health benefit has been corre- eye an almond-shaped appearance. lated with the presence of an extra copy of the DSCR1 gene, M06_KLUG8414_10_SE_C06.indd 102 16/11/18 5:12 pm  6.2 MONOSOMY AND TRISOMY RESULT IN A VARIETY OF PHENOTYPIC EFFECTS 103 which encodes a protein that suppresses vascular endothelial is noted at age 40. The frequency increases still further to growth factor (VEGF). This suppression, in turn, blocks the about 1 in 30 at age 45. A very alarming statistic is that as process of angiogenesis. As a result, the overexpression of the age of childbearing women exceeds 45, the probability this gene inhibits tumors from forming proper vasculariza- of a child born with Down syndrome continues to increase tion, diminishing their growth. A 14-year study published in substantially. In spite of this high probability, substantially 2002 involving 17,800 Down syndrome individuals revealed more than half of such births occur to women younger than an approximate 10 percent reduction in cancer mortality in 35 years, because the overwhelming proportion of preg- contrast to a control population. nancies in the general population involve women under that age. The Origin of the Extra 21st Chromosome in Although the nondisjunctional event that produces Down Syndrome Down syndrome seems more likely to occur during oogenesis Most frequently, this trisomic condition occurs through in women over the age of 35, we do not know with certainty nondisjunction of chromosome 21 during meiosis. Failure of why this is so. However, one observation may be relevant. paired homologs to disjoin during either anaphase I or II may Meiosis is initiated in all the eggs of a human female when lead to gametes with the n + 1 chromosome composition. she is still a fetus, until the point where the homologs syn- About 75 percent of these errors leading to Down syndrome apse and recombination has begun. Then oocyte develop- are attributed to nondisjunction during the first meiotic ment is arrested in meiosis I. Thus, all primary oocytes have division. Subsequent fertilization with a normal gamete cre- been formed by birth. When ovulation begins at puberty, ates the trisomic condition. meiosis is reinitiated in one egg during each ovulatory cycle Chromosome analysis has shown that, while the addi- and continues into meiosis II. The process is once again tional chromosome may be derived from either the mother arrested after ovulation and is not completed unless fertil- or father, the ovum is the source in about 95 percent of 47, ization occurs. 21+ trisomy cases. Before the development of techniques The end result of this progression is that each ovum that using polymorphic markers to distinguish paternal from is released has been arrested in meiosis I for about a month maternal homologs, this conclusion was supported by the longer than the one released during the preceding cycle. As a more indirect evidence derived from studies of the age consequence, women 30 or 40 years old produce ova that are of mothers giving birth to infants with Down syndrome. significantly older and that have been arrested longer than Figure 6.3 shows the relationship between the incidence those they ovulated 10 or 20 years previously. In spite of of children born with Down syndrome and maternal age, the logic underlying this hypothesis explaining the cause of illustrating the dramatic increase as the age of the mother the increased incidence of Down syndrome as women age,!it increases. While the frequency is about 1 in 1000 at mater- remains difficult to prove directly. nal age 30, a tenfold increase to a frequency of 1 in 100 These statistics obviously pose a serious problem for the woman who becomes pregnant late in her reproduc- tive years. Genetic counseling early in such pregnancies is highly recommended. Counseling informs prospective par- 70 1/15 ents about the probability that their child will be affected and educates them about Down syndrome. Although some Down syndrome per 1000 births individuals with Down syndrome experience moderate to 52 severe cognitive delays, most experience only mild to mod- erate delays. These individuals are increasingly integrated into society, including school, the work force, and social and 35 recreational activities. A genetic counselor may also recom- 1/30 mend a prenatal diagnostic technique in which fetal cells are isolated and cultured. In amniocentesis and chorionic villus sampling 17 (CVS), the two most familiar approaches, fetal cells are 10/1000 obtained from the amniotic fluid or the chorion of the pla- 3/1000 centa, respectively. In a newer approach, fetal cells and DNA are derived directly from the maternal circulation, a 20 25 30 35 40 45 50 technique referred to as noninvasive prenatal genetic Maternal age (years) diagnosis (NIPGD). Requiring only a 10-mL maternal blood F I G U R E 6. 3 Incidence of children born with Down sample, this procedure will become increasingly more com- syndrome related to maternal age. mon because it poses no risk to the fetus. After fetal cells M06_KLUG8414_10_SE_C06.indd 103 16/11/18 5:12 pm 104 6 CHROMOSOME MUTATIONS: VARIATION IN NUMBER AND ARRANGEMENT are obtained and cultured, the karyotype can be deter- case has been confirmed by karyotypic analysis of sponta- mined by cytogenetic analysis. If the fetus is diagnosed as neously aborted fetuses. These studies reveal two striking being affected, further counseling for parents will be offered statistics: (1) Approximately 20 percent of all conceptions regarding the options open to them, one of which is abortion terminate in spontaneous abortion (some estimates are of the fetus. Obviously, this is a difficult decision involving considerably higher); and (2) about 30 percent of all spon- both religious and ethical issues. taneously aborted fetuses demonstrate some form of chro- Since Down syndrome is caused by a random error—non- mosomal imbalance. This suggests that at least 6 percent disjunction of chromosome 21 during maternal or paternal (0.20 * 0.30) of conceptions contain an abnormal chromo- meiosis—the occurrence of the disorder is not expected to be some complement. A large percentage of fetuses demon- inherited. Nevertheless, Down syndrome occasionally runs in strating chromosomal abnormalities are aneuploids. families. These instances, referred to as familial Down syndrome, An extensive review of this subject by David H. Carr has involve a translocation of chromosome 21, another type of chro- revealed that a significant percentage of aborted fetuses are mosomal aberration, which we will discuss later in the chapter. trisomic for one of the chromosome groups. Trisomies for every human chromosome have been recovered. Interest- ingly, the monosomy with the highest incidence among abor- Human Aneuploidy tuses is the 45,X condition, which produces an infant with Besides Down syndrome, only two human trisomies, and no Turner syndrome if the fetus survives to term. Autosomal autosomal monosomies, survive to term: Patau and Edwards monosomies are seldom found, however, even though non- syndromes (47, 13+ and 47, 18+, respectively). Even so, disjunction should produce n - 1 gametes with a frequency these individuals manifest severe malformations and early equal to n + 1 gametes. This finding suggests that gametes lethality. Figure 6.4 illustrates the abnormal karyotype and lacking a single chromosome are functionally impaired to a the many defects characterizing infants with Patau syndrome. serious degree or that the embryo dies so early in its devel- The preceding observation leads us to ask whether opment that recovery occurs infrequently. We discussed the many other aneuploid conditions arise but that the potential causes of monosomic lethality earlier in this chap- affected fetuses do not survive to term. That this is the ter. Carr’s study also found various forms of polyploidy and other miscellaneous chromosomal anomalies. These observations support the hypothesis that normal embryonic development requires a precise diploid comple- ment of chromosomes to maintain the delicate equilibrium in the expression of genetic information. The prenatal mortality of most aneuploids provides a barrier against the introduc- tion of these genetic anomalies into the human population. ES S ENTIA L POIN T Studies of monosomic and trisomic disorders are increasing our understanding of the delicate genetic balance that is essential for normal development. 6.3 Polyploidy, in Which More Than Intellectual disability Microcephaly Growth failure Cleft lip and palate Two Haploid Sets of Chromosomes Low-set, deformed ears Polydactyly Are Present, Is Prevalent in Plants Deafness Deformed finger nails Atrial septal defect Kidney cysts The term polyploidy describes instances in which more than Ventricular septal Double ureter defect two multiples of the haploid chromosome set are found. Umbilical hernia Abnormal Developmental uterine The naming of polyploids is based on the number of sets of polymorphonuclear abnormalities chromosomes found: A triploid has 3n chromosomes; a tet- granulocytes Cryptorchidism raploid has 4n; a pentaploid, 5n; and so forth (Table 6.1). Several general statements can be made about polyploidy. F I G U R E 6. 4 The karyotype and phenotypic description of This condition is relatively infrequent in many animal spe- an infant with Patau syndrome, where three members of the D-group chromosome 13 are present, creating the 47, 13 + cies but is well known in lizards, amphibians, and fish, and is condition. much more common in plant species. Usually, odd numbers  6.3 POLYPLOIDY, IN WHICH MORE THAN TWO HAPLOID SETS OF CHROMOSOMES ARE PRESENT 105 of chromosome sets are not reliably maintained from gen- chromosomes, while tetraploids produce 2n gametes. Upon eration to generation because a polyploid organism with an fertilization, the desired triploid is produced. uneven number of homologs often does not produce geneti- Because they have an even number of chromosomes, cally balanced gametes. For this reason, triploids, penta- autotetraploids (4n) are theoretically more likely to be ploids, and so on, are not usually found in plant species that found in nature than are autotriploids. Unlike triploids, depend solely on sexual reproduction for propagation. which often produce genetically unbalanced gametes with Polyploidy originates in two ways: (1) The addition odd numbers of chromosomes, tetraploids are more likely of one or more extra sets of chromosomes, identical to the to produce balanced gametes when involved in sexual normal haploid complement of the same species, resulting reproduction. in autopolyploidy; or (2) the combination of chromosome How polyploidy arises naturally is of great interest to sets from different species occurring as a consequence of geneticists. In theory, if chromosomes have replicated, but hybridization, resulting in allopolyploidy (from the Greek the parent cell never divides and instead reenters inter- word allo, meaning “other” or “different”). The distinction phase, the chromosome number will be doubled. That this between auto- and allopolyploidy is based on the genetic ori- very likely occurs is supported by the observation that tet- gin of the extra chromosome sets, as shown in Figure 6.5. raploid cells can be produced experimentally from diploid In our discussion of polyploidy, we use the following cells. This is accomplished by applying cold or heat shock symbols to clarify the origin of additional chromosome sets. to meiotic cells or by applying colchicine to somatic cells For example, if A represents the haploid set of chromosomes undergoing mitosis. Colchicine, an alkaloid derived from of any organism, then the autumn crocus, interferes with spindle formation, and thus replicated chromosomes cannot separate at anaphase A = a1 + a2 + a3 + a4 + g + an and do not migrate to the poles. When colchicine is removed, where a1, a2, and so on, are individual chromosomes and n the cell can reenter interphase. When the paired sister chro- is the haploid number. A normal diploid organism is repre- matids separate and uncoil, the nucleus contains twice the sented simply as AA. diploid number of chromosomes and is therefore 4n. This process is shown in Figure 6.6. In general, autopolyploids are larger than their diploid Autopolyploidy relatives. This increase seems to be due to larger cell size In autopolyploidy, each additional set of chromosomes is rather than greater cell number. Although autopolyploids identical to the parent species. Therefore, triploids are rep- do not contain new or unique information compared with resented as AAA, tetraploids are AAAA, and so forth. their diploid relatives, the flower and fruit of plants are Autotriploids arise in several ways. A failure of all often increased in size, making such varieties of greater chromosomes to segregate during meiotic divisions can horticultural or commercial value. Economically important produce a diploid gamete. If such a gamete is fertilized by triploid plants include several potato species of the genus a haploid gamete, a zygote with three sets of chromosomes Solanum, Winesap apples, commercial bananas, seedless is produced. Or, rarely, two sperm may fertilize an ovum, watermelons, and the cultivated tiger lily Lilium tigrinum. resulting in a triploid zygote. Triploids are also produced These plants are propagated asexually. Diploid bananas under experimental conditions by crossing diploids with contain hard seeds, but the commercial, triploid, “seedless” tetraploids. Diploid organisms produce gametes with n variety has edible seeds. Tetraploid alfalfa, coffee, peanuts, F I G UR E 6. 5 Contrasting chromosome Autopolyploidy Allopolyploidy origins of an autopolyploid versus an Diploid Diploid Diploid allopolyploid karyotype. * Triploid Tetraploid Tetraploid M06_KLUG8414_10_SE_C06.indd 105 16/11/18 5:12 pm  106 6 CHROMOSOME MUTATIONS: VARIATION IN NUMBER AND ARRANGEMENT F I G U R E 6. 6 The potential involvement of Diploid Tetraploid colchicine in doubling the chromosome number. Two pairs of homologous chromo- somes are shown. While each chromosome had replicated its DNA earlier during inter- phase, the chromosomes do not appear as double structures until late prophase. When anaphase fails to occur normally, the chromosome number doubles if the cell reenters interphase. Early prophase Late prophase Cell subsequently reenters interphase Colchicine added Colchicine removed and McIntosh apples are also of economic value because fertile AABB tetraploid is produced. These events are shown they are either larger or grow more vigorously than do their in Figure 6.7. Since this polyploid contains the equivalent diploid or triploid counterparts. Many of the most popular of four haploid genomes derived from separate species, such varieties of hosta plant are tetraploid. In each case, leaves an organism is called an allotetraploid. When both origi- are thicker and larger, the foliage is more vivid, and the nal species are known, an equivalent term, amphidiploid, plant grows more vigorously. The commercial strawberry is preferred in describing the allotetraploid. is an octoploid. How cells with increased ploidy values express differ- ent phenotypes from their diploid counterparts has been Species 1 Species 2 investigated. Gerald Fink and his colleagues created strains of the yeast Saccharomyces cerevisiae with one, two, three, or a1 a2 a3 b1 b2 AA a1 a2 a3 * BB b1 b2 four copies of the genome and then examined the expression levels of all genes during the cell cycle. Using the stringent Gamete formation standards of at least a tenfold increase or decrease of gene A a1 B expression, Fink and coworkers identified numerous cases a2 b1 b2 a3 where, as ploidy increased, gene expression either increased Fertilization or decreased at least tenfold. Among these cases are two genes that encode G1 cyclins, which are repressed when ploidy increases. G1 cyclins facilitate the cell’s movement through a1 a2 a3 AB b1 b2 G1 of the cell cycle, which is thus delayed when expression of these genes is repressed. The polyploid cell stays in the G1 Sterile hybrid phase longer and, on average, grows to a larger size before it Chromosome doubling moves beyond the G1 stage of the cell cycle, providing a clue a1a1 a2a2 a3a3 as to how other polyploids demonstrate increased cell size. b1b1 b2b2 AABB Fertile amphidiploid Allopolyploidy Polyploidy can also result from hybridizing two closely Gamete formation related species. If a haploid ovum from a species with chro- mosome sets AA is fertilized by sperm from a species with sets a1a2a3 a1a2a3 BB, the resulting hybrid is AB, where A = a1, a2, a3, c , an b1b2 b1 b2 and B = b1, b2, b3, c , bn. The hybrid organism may be ster- ile because of its inability to produce viable gametes. Most AB AB often, this occurs when some or all of the a and b chromo- FI G U R E 6.7 The origin and propagation of an somes are not homologous and therefore cannot synapse in amphidiploid. Species 1 contains genome A consist- meiosis. As a result, unbalanced genetic conditions result. ing of three distinct chromosomes, a1, a2, and a3. If, however, the new AB genetic combination undergoes a Species 2 contains genome B consisting of two dis- natural or an induced chromosomal doubling, two copies of tinct chromosomes, b1 and b2. Following fertilization between members of the two species and chromo- all a chromosomes and two copies of all b chromosomes will some doubling, a fertile amphidiploid containing be present, and they will pair during meiosis. As a result, a two complete diploid genomes (AABB) is formed. M06_KLUG8414_10_SE_C06.indd 106 16/11/18 5:12 pm  6.4 VARIATION OCCURS IN THE COMPOSITION AND ARRANGEMENT OF CHROMOSOMES 107 Amphidiploid plants are often found in nature. Their Using the technique outlined in Figure 6.7, geneticists reproductive success is based on their potential for forming have produced various hybrids. When tetraploid wheat is balanced gametes. Since two homologs of each specific chro- crossed with diploid rye and the F1 plants are treated with mosome are present, meiosis occurs normally (Figure!6.7) colchicine, a hexaploid variety (6n = 42) is obtained; the and fertilization successfully propagates the plant sexually. hybrid, designated Triticale, represents a new genus. Other This discussion assumes the simplest situation, where none Triticale varieties have been created. These hybrid plants of the chromosomes in set A are homologous to those in set B. demonstrate characteristics of both wheat and rye. For In amphidiploids formed from closely related species, some example, they combine the high-protein content of wheat homology between a and b chromosomes is likely. Allopoly- with rye’s high content of the amino acid lysine, which is ploids are rare in most animals because mating behavior low in wheat and thus is a limiting nutritional factor. Wheat is most often species-specific, and thus the initial step in is considered to be a high-yielding grain, whereas rye is hybridization is unlikely to occur. noted for its versatility of growth in unfavorable environ- A classical example of amphidiploidy in plants is the cul- ments. Triticale species that combine both traits have the tivated species of American cotton, Gossypium (Figure 6.8). potential of significantly increasing grain production. This This species has 26 pairs of chromosomes: 13 are large and and similar programs designed to improve crops through 13 are much smaller. When it was discovered that Old hybridization have long been under way in several develop- World cotton had only 13 pairs of large chromosomes, allo- ing countries. polyploidy was suspected. After an examination of wild American cotton revealed 13 pairs of small chromosomes, this speculation was strengthened. J. O. Beasley recon- N O W S O LV E T H I S structed the origin of cultivated cotton experimentally by 6.2 When two plants belonging to the same genus but dif- crossing!the Old World strain with the wild American strain ferent species are crossed, the F1 hybrid is viable and has and then treating the hybrid with colchicine to double the more ornate flowers. Unfortunately, this hybrid is sterile chromosome number. The result of these treatments was a and can only be propagated by vegetative cuttings. Explain fertile amphidiploid variety of cotton. It contained 26 pairs the sterility of the hybrid and what would have to occur for of chromosomes as well as characteristics similar to the cul- the sterility of this hybrid to be reversed. tivated variety. H I NT: This problem involves an understanding of allopolyploid Amphidiploids often exhibit traits of both paren- plants. The key to its solution is to focus on the origin and com- tal species. An interesting example involves the grasses position of the chromosomes in the F1 and how they might be wheat and rye. Wheat (genus Triticum) has a basic haploid manipulated. genome of seven chromosomes. In addition to normal dip- loids (2n = 14), cultivated autopolyploids exist, including tetraploid (4n = 28) and hexaploid (6n = 42) species. Rye (genus Secale) also has a genome consisting of seven chro- ES S ENTIA L POIN T mosomes. The only cultivated species is the diploid plant When complete sets of chromosomes are added to the diploid (2n = 14). genome, these sets can have an identical or a diverse genetic origin, creating either autopolyploidy or allopolyploidy, respectively. 6.4 Variation Occurs in the Composition and Arrangement of Chromosomes The second general class of chromosome aberrations includes changes that delete, add, or rearrange substan- tial portions of one or more chromosomes. Included in this broad category are deletions and duplications of genes or part of a chromosome and rearrangements of genetic material in which a chromosome segment is inverted, F I G U R E 6. 8 The pods of the amphidiploid form of Gossy- exchanged with a segment of a nonhomologous chromo- pium, the cultivated American cotton plant. some, or merely transferred to another chromosome. 108 6 CHROMOSOME MUTATIONS: VARIATION IN NUMBER AND ARRANGEMENT Exchanges and transfers are called translocations, in pairing arrangements often lead to gametes that are dupli- which the locations of genes!are altered within the genome. cated or deficient for some chromosomal regions. When this These types of chromosome alterations are illustrated in occurs, the offspring of “carriers” of certain aberrations Figure 6.9. have an increased probability of demonstrating phenotypic In most instances, these structural changes are due changes. to one or more breaks along the axis of a chromosome, followed by either the loss or rearrangement of genetic material. Chromosomes can break spontaneously, but the rate of breakage may increase in cells exposed to chemi- 6.5 A Deletion Is a Missing Region cals or radiation. The ends produced at points of breakage of a Chromosome are “sticky” and can rejoin other broken ends. If breakage and rejoining do not reestablish the original relationship When a chromosome breaks in one or more places and a and if the alteration occurs in germ plasm, the gametes portion of it is lost, the missing piece is called a deletion will contain the structural rearrangement, which is (or a deficiency). The deletion can occur either near heritable. one end or within the interior of the chromosome. These If the aberration is found in one homolog but not the are terminal and intercalary deletions, respectively other, the individual is said to be heterozygous for the aber- [Figure 6.10(a) and (b)]. The portion of the chromosome ration. In such cases, unusual but characteristic pairing that retains the centromere region is usually maintained configurations are formed during meiotic synapsis. These when the cell divides, whereas the segment without the patterns are useful in identifying the type of change that has centromere is eventually lost in progeny cells following occurred. If no loss or gain of genetic material occurs, indi- mitosis or meiosis. For synapsis to occur between a chro- viduals bearing the aberration “heterozygously” are likely mosome with a large intercalary deletion and a normal to be unaffected phenotypically. However, the unusual homolog, the unpaired region of the normal homolog must F I G U R E 6. 9 An overview (a) Deletion of D (b) Duplication of BC (c) Inversion of BCD of the five different types of gain, loss, or rear- rangement of chromo- A A A A A A some segments. B B B B B D C C C C C C Deletion Duplication Inversion D E D B D B E E C E E F D F G F F F E G G G G F G (d) Nonreciprocal translocation of AB (e) Reciprocal translocation of AB and HIJ A H C A A H H A B I D B B I I B C J Nonreciprocal E H C J Reciprocal J translocation translocation K + + + + D K I D K C F L E L J E L D G M K E F M F M L G G F M G Nonhomologous Nonhomologous chromosomes chromosomes  6.5 A DELETION IS A MISSING REGION OF A CHROMOSOME 109 (a) Origin of terminal deletion aberration is often lethal, in which case the chromosome A B C D E F B C D E F mutation never becomes available for study. A + Break (Lost) Cri du Chat Syndrome in Humans (b) Origin of intercalary deletion In humans, the cri du chat syndrome results from the D C D C deletion of a small terminal portion of chromosome 5. It Break Break might be considered a case of partial monosomy, but since A B E F A B E F the region that is missing is so small, it is better referred to as a segmental deletion. This syndrome was first reported A B E F D C + by Jérôme Lejeune in 1963, when he described the clinical Deleted chromosome (Lost) symptoms, including an eerie cry similar to the meowing of a cat, after which the syndrome is named. This syndrome is (c) Formation of deletion loop associated with the loss of a small, variable part of the short arm of chromosome 5 (Figure 6.11). Thus, the genetic con- Area missing in deleted chromosome stitution may be designated as 46,5p–, meaning that the C D individual has all 46 chromosomes but that some or all of A B C D E F A B E F the p arm (the petite, or short, arm) of one member of the Normal chromosome Synapsis chromosome 5 pair is missing. A B E F Infants with this syndrome exhibit intellectual disabil- A B E F Homolog with deleted Formation of deletion loop ity, delayed development, small head size, and distinctive regions C and D facial features in addition to abnormalities in the glottis and larynx, leading to the characteristic crying sound. F I G U R E 6.10 Origins of (a) a terminal and (b) an inter- Since 1963, hundreds of cases of cri du chat syn- calary deletion. In (c), pairing occurs between a normal chromosome and one with an intercalary deletion by drome have been reported worldwide. An incidence of 1 in looping out the undeleted portion to form a deletion (or 20,000–50,000 live births has been estimated. Most often, compensation) loop. the condition is not inherited but instead results from the sporadic loss of chromosomal material in gametes. The “buckle out” into a deletion, or compensation, loop length of the short arm that is deleted varies somewhat; [Figure 6.10(c)]. longer deletions tend to result in more severe intellectual If only a small part of a chromosome is deleted, the disability and developmental delay. Although the effects of organism might survive. However, a deletion of a portion the syndrome are severe, most individuals achieve motor of a chromosome need not be very great before the effects and language skills. The deletion of several genes, including become severe. We see an example of this in the following the telomerase reverse transcriptase (TERT) gene, has been discussion of the cri du chat syndrome in humans. If even implicated in various phenotypic changes in cri du chat more genetic information is lost as a result of a deletion, the syndrome. FI G U R E 6.11 A representative karyotype and a photograph of a child with cri du chat syndrome (46,5p—). In the karyotype, the arrow identifies the absence of a small piece of the short arm of one member of the chromosome 5 homologs. M06_KLUG8414_10_SE_C06.indd 109 16/11/18 5:12 pm 110 6 CHROMOSOME MUTATIONS: VARIATION IN NUMBER AND ARRANGEMENT Such DNA is called rDNA, and the general phenomenon is 6.6 A Duplication Is a Repeated referred to as gene redundancy. For example, in the com- Segment of a Chromosome mon intestinal bacterium Escherichia coli (E. coli), about 0.7 percent of the haploid genome consists of rDNA—the equivalent of seven copies of the gene. In Drosophila mela- When any part of the genetic material—a single locus or a nogaster, 0.3 percent of the haploid genome, equivalent to large piece of a chromosome—is present more than once in 130 gene copies, consists of rDNA. Although the presence the genome, it is called a duplication. As in deletions, pairing of multiple copies of the same gene is not restricted to those in heterozygotes can produce a compensation loop. Duplica- coding for rRNA, we will focus on them in this section. tions may arise as the result of unequal crossing over between In some cells, particularly oocytes, even the normal synapsed chromosomes during meiosis (Figure 6.12) or amplification of rDNA is insufficient to provide adequate through a replication error prior to meiosis. In the former amounts of rRNA needed to construct ribosomes. For exam- case, both a duplication and a deletion are produced. ple, in the amphibian Xenopus laevis, 400 copies of rDNA We consider three interesting aspects of duplications. are present per haploid genome. These genes are all found First, they may result in gene redundancy. Second, as with in a single area of the chromosome known as the nucleolar deletions, duplications may produce phenotypic variation. organizer region (NOR). In Xenopus oocytes, the NOR is Third, according to one convincing theory, duplications selectively replicated to further increase rDNA copies, and have also been an important source of genetic variability each new set of genes is released from its template. Each during evolution. set forms a small nucleolus, and as many as 1500 of these “micronucleoli” have been observed in a single oocyte. If we Gene Redundancy—Ribosomal RNA Genes multiply the number of micronucleoli (1500) by the number of gene copies in each NOR (400), we see that amplification Although many gene products are not needed in every cell of in Xenopus oocytes can result in over half a million gene cop- an organism, other gene products are known to be essential ies! If each copy is transcribed only 20 times during the mat- components of all cells. For example, ribosomal RNA must uration of the oocyte, in theory, sufficient copies of rRNA are be present in abundance to support protein synthesis. The produced to result in well over 12 million ribosomes. more metabolically active a cell is, the higher the demand for this molecule. We might hypothesize that a single copy of the gene encoding rRNA is inadequate in many cells. Stud- The Bar Mutation in Drosophila ies using the technique of molecular hybridization, which Duplications can cause phenotypic variation that might at enables us to determine the percentage of the genome that first appear to be caused by a simple gene mutation. The codes for specific RNA sequences, show that our hypothesis Bar-eye phenotype in Drosophila (Figure 6.13) is a classic is correct. Indeed, multiple copies of genes code for rRNA. example. Instead of the normal oval-eye shape, Bar-eyed flies have narrow, slit-like eyes. This phenotype is inherited in the same way as a dominant X-linked mutation. 3 4 1 2 3 4 1 2 In the early 1920s, Alfred H. Sturtevant and Thomas A A A A A A H. Morgan discovered and investigated this “mutation.” A A B B B B B B Normal wild-type females (B+ >B+) have about 800 facets in B B C each eye. Heterozygous females (B>B+) have about 350!fac- C C D C C ets, while homozygous females (B>B) average only about C C D D D E C D 70!facets. Females were occasionally recovered with even D D fewer facets and were designated as double Bar (BD >B+) E E E F D E E E About 10 years later, Calvin Bridges and Herman J. F E F Muller compared the polytene X chromosome banding F F F F pattern of the Bar fly with that of the wild-type fly. These F chromosomes contain specific banding patterns that have been well categorized into regions. Their studies revealed F I G U R E 6. 1 2 The origin of duplicated and deficient that one copy of the region designated as 16A is present on regions of chromosomes as a result of unequal crossing over. The tetrad on the left is mispaired during synapsis. A both X chromosomes of wild-type flies but that this region single crossover between chromatids 2 and 3 results in the was duplicated in Bar flies and triplicated in double Bar flies. deficient (chromosome 2) and duplicated (chromosome 3) These observations provided evidence that the Bar pheno- chromosomal regions shown on the right. The two chromo- somes uninvolved in the crossover event remain normal in type is not the result of a simple chemical change in the gene gene sequence and content. but is instead a duplication.  6.6 A DUPLICATION IS A REPEATED SEGMENT OF A CHROMOSOME 111 F IG U R E 6. 13 Bar-eye phenotypes in contrast to the wild-type eye in Drosophila (shown in the left panel). B +/B + B/B + B/B The Role of Gene Duplication in Evolution conclude that they share a common origin and arose through the process of gene duplication. One of the most interest- During the study of evolution, it is intriguing to speculate ing supporting examples is the case of the SRGAP2 gene in on the possible mechanisms of genetic variation. The origin primates. This gene is known to be involved in the develop- of unique gene products present in more recently evolved ment of the brain. Humans have at least four similar cop- organisms but absent in ancestral forms is a topic of particu- ies of the gene, while all nonhuman primates have only a lar interest. In other words, how do “new” genes arise? single copy. Several duplication events can be traced back In 1970, Susumo Ohno published a provocative mono- to 3.4 million years ago, to 2.4 million years ago, and finally graph, Evolution by Gene Duplication, in which he suggested to 1 million years ago, resulting in distinct forms of SRGAP2 that gene duplication is essential to the origin of new genes labeled A–D. These evolutionary periods coincide with the during evolution. Ohno’s thesis is based on the supposition emergence of the human lineage in primates. The function that the gene products of many genes, present as only a sin- of these genes has now been related to the regulation and gle copy in the genome, are indispensable to the survival of formation of dendritic spines in the brain, which is believed members of any species during evolution. Therefore, unique to contribute to the evolution of expanded brain function in genes are not free to accumulate mutations sufficient to alter humans, including the development of language and social their primary function and give rise to new genes. cognition. However, if an essential gene is duplicated in the germ Other examples of gene families arising from duplica- line, major mutational changes in this extra copy will be tion during evolution include the various types of human tolerated in future generations because the original gene hemoglobin polypeptide chains, as well as the immunologi- provides the genetic information for its essential function. cally important T-cell receptors and antigens encoded by the The duplicated copy will be free to acquire many muta- major histocompatibility complex. tional changes over extended periods of time. Over short intervals, the new genetic information may be of no practi- cal advantage. However, over long evolutionary periods, the duplicated gene may change sufficiently so that its product Duplications at the Molecular Level: Copy assumes a divergent role in the cell. The new function may Number Variations (CNVs) impart an “adaptive” advantage to organisms, enhancing As we entered the era of genomics and became capable of their fitness. Ohno has outlined a mechanism through which sequencing entire genomes (see Chapter 17), we quickly sustained genetic variability may have originated. realized that duplications of portions of genes, most often Ohno’s thesis is supported by the discovery of genes that involving thousands of base pairs, occur on a regular basis. have a substantial amount of their organization and DNA When individuals in the same species are compared, the sequence in common, but whose gene products are distinct. number of copies of any given duplicated sequence within a For example, trypsin and chymotrypsin fit this description, given gene is found to differ—sometimes there are larger and as do myoglobin and the various forms of hemoglobin. The sometimes smaller numbers of copies, a condition described DNA sequence is so similar (homologous) in each case that as copy number variation (CNV). Such duplications are we may conclude that members of each pair of genes arose found in both coding and noncoding regions of the genome. from a common ancestral gene through duplication. During CNVs are of major interest in genetics because they are evolution, the related genes diverged sufficiently that their now believed to play crucial roles in the expression of many products became unique. of our individual traits, in both normal and diseased indi- Other support includes the presence of multigene viduals. Currently, when CNVs of sizes ranging from 50 bp to families—groups of contiguous genes whose products per- 3 Mb are considered, it is estimated that they occupy between form the same, or very similar functions. Again, members 5–10 percent of the human genome. Current studies have of a family show DNA sequence homology sufficient to focused on finding associations with human diseases. CNVs M06_KLUG8414_10_SE_C06.indd 111 16/11/18 5:12 pm 112 6 CHROMOSOME MUTATIONS: VARIATION IN NUMBER AND ARRANGEMENT appear to have both positive and negative associations with inversion requires breaks at two points along the length of many diseases in which the genetic basis is not yet fully the chromosome and subsequent reinsertion of the inverted understood. For example, pathogenic CNVs have been asso- segment. Figure 6.14 illustrates how an inversion might ciated with autism and other neurological disorders, and arise. By forming a chromosomal loop prior to breakage, with cancer. Additionally, CNVs are suspected to be associ- the newly created “sticky ends” are brought close together ated with Type I diabetes and cardiovascular disease. and rejoined. In some cases, entire gene sequences are duplicated and The inverted segment may be short or quite long and impact individuals. For example, a higher-than-average may or may not include the centromere. If the centro- copy number of the gene CCL3L1 imparts an HIV-suppres- mere is not part of the rearranged chromosome segment, sive effect during viral infection, diminishing the progres- it is a paracentric inversion, which is the type shown in sion to AIDS. Another finding has associated specific mutant Figure 6.14. If the centromere is part of the inverted seg- CNV sites with certain subset populations of individuals ment, it is described as a pericentric inversion. with lung cancer—the greater number of copies of the EGFR (Epidermal Growth Factor Receptor) gene, the more respon- sive are patients with non-small-cell lung cancer to treat- Consequences of Inversions during Gamete ment. Finally, the greater the reduction in the copy number Formation of the gene designated DEFB, the greater the risk of develop- If only one member of a homologous pair of chromosomes ing Crohn’s disease, a condition affecting the colon. Relevant has an inverted segment, normal linear synapsis during mei- to this chapter, these findings reveal that duplications and osis is not possible. Organisms with one inverted chromo- deletions are no longer restricted to textbook examples of some and one noninverted homolog are called inversion these chromosomal mutations. We will return to this inter- heterozygotes. Pairing between two such chromosomes in esting topic later in the text (see Chapter 18), when genomics meiosis is accomplished only if they form an inversion loop is discussed in detail. (Figure 6.15). If crossing over does not occur within the inverted seg- ment of the inversion loop, the homologs will segregate, ES S ENTIAL P OINT which results in two normal and two inverted chromatids Deletions or duplications of segments of a gene or a chromosome may be the source of mutant phenotypes such as cri du chat syn- that are distributed into gametes. However, if crossing over drome in humans and Bar eyes in Drosophila, while duplications can does occur within the inversion loop, abnormal chromatids be particularly important as a source of redundant or new genes. are produced. The effect of a single crossover (SCO) event within a paracentric inversion is diagrammed in Figure 6.15. In any meiotic tetrad, a single crossover between non- sister chromatids produces two parental chromatids and 6.7 Inversions Rearrange the Linear two recombinant chromatids. When the crossover occurs Gene Sequence within a paracentric inversion, however, one recombi- nant dicentric chromatid (two centromeres) and one The inversion, another class of structural variation, is a recombinant acentric chromatid (lacking a centromere) type of chromosomal aberration in which a segment of a are produced. Both contain duplications and deletions of chromosome is turned around 180 degrees within a chromo- chromosome segments as well. During anaphase, an acentric some. An inversion does not involve a loss of genetic infor- chromatid moves randomly to one pole or the other or may be mation but simply rearranges the linear gene sequence. An lost, while a dicentric chromatid is pulled in two directions. A B C D E F A E D C B F FI G U R E 6.1 4 One possible origin of a paracentric inversion. Inverted sequence A F A F A F E B Gaps E B E B Break created Rejoining D C D C D C  6.8 TRANSLOCATIONS ALTER THE LOCATION OF CHROMOSOMAL SEGMENTS IN THE GENOME 113 Paracentric inversion heterozygote adjacent loci within inversions may be preserved from gen- A B C D E F eration to generation. If the alleles of the involved genes 1 1' confer a survival advantage on the organisms maintaining 2 2' A B C D E F them, the inversion is beneficial to the evolutionary sur- a d c b e f 3 3' vival of the species. For example, if a set of alleles ABcDef is 4 4' more adaptive than sets AbCdeF or abcdEF, effective gam- a d c b e f etes will contain this favorable set of genes, undisrupted by crossing over. Inversion loop, including crossover In laboratory studies, the same principle is applied C C using balancer chromosomes, which contain inversions. B c D When an organism is heterozygous for a balancer chromo- B D A b c d E F some, desired sequences of alleles are preserved during 1 b d 1' A E F experimental work. 2 2' a e f 3 3' a e f 4 4' N O W S O LV E T H I S 6.3 What is the effect of a rare double crossover within a Resultant gametes chromosome segment that is heterozygous for a paracen- A B C D E F tric inversion? 1 1' NCO Normal sequence A B C d a SCO Dicentric; H I NT: This problem involves an understanding of how homologs 2 4 duplication and deletion synapse in the presence of a heterozygous paracentric inversion. a d c b e f The key to its solution is to draw out the tetrad and follow the 3 3' NCO Inverted sequence chromatids undergoing a double crossover. f e b c D E F 4‘ 2' SCO Acentric; duplication and deletion F I G U R E 6. 1 5 The effects of a single crossover (SCO) within an inversion loop in a paracentric inversion hetero- 6.8 Translocations Alter the Location zygote, where two altered chromosomes are produced, one acentric and one dicentric. Both chromosomes also contain of Chromosomal Segments in the duplicated and deficient regions. Genome This polarized movement produces dicentric bridges that are Translocation, as the name implies, is the movement of cytologically recognizable. A dicentric chromatid usually a chromosomal segment to a new location in the genome. breaks at some point so that part of the chromatid goes into Reciprocal translocation, for example, involves the exchange one gamete and part into another gamete during the meiotic of segments between two nonhomologous chromosomes. divisions. Therefore, gametes containing either recombi- The least complex way for this event to occur is for two non- nant chromatid are deficient in genetic material. In animals, homologous chromosome arms to come close to each other when such a gamete participates in fertilization, the zygote so that an exchange is facilitated. Figure 6.16(a) shows a most often develops abnormally, if at all. simple reciprocal translocation in which only two breaks are Because offspring bearing crossover gametes are invi- required. If the exchange includes internal chromosome seg- able and not recovered, it appears as if the inversion sup- ments, four breaks are required, two on each chromosome. presses crossing over. Actually, in inversion heterozygotes, The genetic consequences of reciprocal translocations the inversion has the effect of suppressing the recovery of cross- are, in several instances, similar to those of inversions. For over products when chromosome exchange occurs within the example, genetic information is not lost or gained. Rather, inverted region. Moreover, up to one-half of the viable gam- there is only a rearrangement of genetic material. The pres- etes have the inverted chromosome, and the inversion will ence of a translocation does not, therefore, directly alter the be perpetuated within the species. The cycle will be repeated viability of individuals bearing it. continuously during meiosis in future generations. Homologs that are heterozygous for a recipro- cal translocation undergo unorthodox synapsis during meiosis. As shown in Figure 6.16(b), pairing results in Evolutionary Advantages of Inversions a cross-like configuration. As with inversions, geneti- Because recovery of crossover products is suppressed cally unbalanced gametes are also produced as a result in inversion heterozygotes, groups of specific alleles