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Somatic mutations were examined by studying radiation sickness and cancer among the survivors; germ-line mutations were assessed by looking at birth defects, chromosome abnormalities, and gene mutations in children born to people that had been exposed to radiation. Geneticist James Neel and his colleagues examined almost 19,000 children of people who were within 2000 meters (1. A blood sample was collected from each child, and gel electrophoresis was used to investigate amino acid substitutions in 28 proteins. Of a total of 289,868 genes examined by Neel and his colleagues, only one mutation was found in the children of exposed parents; no mutations were found in the control group. Neel and his colleagues also examined the frequency of chromosome mutations, sex ratios of children born to exposed parents, and frequencies of chromosome aneuploidy. There was no evidence in any of these assays for increased mutations among the children of the people who were exposed to radiation from the atomic explosions, suggesting that germ-line mutations were not elevated. Animal studies clearly show that radiation causes germline mutations; so why was there no apparent increase in germ-line mutations among the inhabitants of Hiroshima and Nagasaki The exposed parents did exhibit an increased incidence of leukemia and other types of cancers; so somatic mutations were clearly induced. The answer to the question is not known, but the lack of germ-line mutations may be due to the fact that those persons who received the largest radiation doses died soon after the blasts. The Techa River in southern Russia is another place where people have been tragically exposed to high levels of radiation. The Mayak nuclear facility produced plutonium for nuclear warheads in the early days of the Cold War. Between 1949 and 1956, this plant dumped some 76 million cubic meters of radioactive sludge into the Techa River. Radiation in the area was further elevated by a series of nuclear accidents at the Mayak plant; the worst was an explosion of a radioactive liquid storage tank in 1957, which 500 Chapter 18 18. Although Soviet authorities suppressed information about the radiation problems along the Techa until the 1990s, Russian physicians led by Mira Kossenko quietly began studying cancer and other radiation-related illnesses among the inhabitants in the 1960s. They found that the overall incidence of cancer was elevated among people who lived on the banks of the Techa River. Most data on radiation exposure in humans are from the intensive study of the survivors of the atomic bombing of Hiroshima and Nagasaki. However, the inhabitants of Hiroshima and Nagasaki were exposed in one intense burst of radiation, and these data may not be appropriate for understanding the effects of long-term low-dose radiation. Some nucleotide T A repeats may form secondary structures on the unpaired strand (see Figure 18. In some eukaryotes, such as yeast and methyl groups on special sequences of the old strand. The process of methylation is delayed and so, tions in mismatch-repair genes often exhibit elevated somatic immediately after replication, the old strand is methylated mutations and are frequently susceptible to colon cancer. Uracil glycosylase, for example, recognizes and removes uracil produced by the deamination of cytosine. Other glycosylases recognize hypoxanthine, 3-methyladenine, 7-methylguanine, and other modified bases. In base-excision repair, glycosylase enzymes recognize and remove specific types of modified bases. The entire nucleotide is then removed and a section of the polynucleotide strand is replaced. It is found in cells of all organisms from bacteria to humans and is among the most important of all repair mechanisms. The process of nucleotide excision is complex; in humans, a large number of genes take part. When a distortion is detected, additional enzymes separate the two nucleotide strands at the damaged region, and single-strand-binding proteins stabilize the separated strands (Figure 18.

And it,vas the common practice ofAlexander to transmit liberal presents to inhabitants of remote places,vho possessed conspicuous virtue" talents, or erudition. This fostering procedure conduced to multiply learned men and excellent artists to such a degree, that scarcely in the age of our own Augustus, did useful enlployments, elegant arts. Nothing is more incontestable, than that the manners and pursuits of the people are influenced by the ex mnple of the prince; and that the inlprovement, or declension, of a nation, reflects honor, or dis grace; upon those,vho govern. He,vas accustomed to carry the Iliad and Odyssey ahvays about his person; and on retiring to bed, laid them, with his svord, un der his pillow; he styled them his "military " Viaticum, and the elenlents of,varlike vir "tue. Among the treasures taken at Damascus, was a casket of inestimable materials and exqui site,vorkmanship, in which the Persian king had kept rare and costly perfumes. His temper,vas cheerful; and he,vas affable to his attendants,vithout sinking to familiarities that would have made him little. He appeared to have extinguished voluptuous wishes, rather than to have regulated them; and from his indifference to the charming half of society, it,vas appre hended that the house of Macedonia,vould be left without an heir. Thessal y,vas then famous for its breed of fine horses, yet none of that country Chap. Philip tegarding so,vild and unmanageable an aniInal as useless, desired that he might he led a,vay, Alexander, ho,vever, on hearing this order, cried out: "vVhat an excellent horse are,ve " going to lose, for,vaht of address and bold. The Medari, inhabiting a city in ~~race subject to 1 Iaceda nia, conceiving the government to have been left in incOlnpetent hands, seized this opportu nity, as favouring a revolt,vhich they had long tp. The sieg~ of Byzantiulll had no,v been pro tracted ~ ~onsiderable time; the bravery of the inhabitants, seconded by succours froln Chios a This spoil, altogether, -,vas of a kind rather to encumber than enrich the victors. To Philip, on his way to Scythia, had been granted an unconditional passage through the country of the Triballi,vho then displayed every appearance of submission t. These peo ple, however, in order to extort a share of the booty,vith which Philip,vas returning-,-hav ing seized all the defiles, opposed his march in. To repeat transactions between Cunning and Fatuity: he l1ad induced the Aclueans and. Sapping further the out,Yorks of Sparta, he had loosened, if not destroyed, the dependence of Arcadia upon the pr~ncipal state t. At length, the people of Attica, alarmed by the encroachments of Philip,vere, by the elo quence of Delnosthenes, continned in the resolu. These transactions ~appened during the extraordinary military preparations in Macedon,vhich pro~ ceeded unremittingly for hvo years. A body of ten thousand mercena ries,vhich they had hired to assist the Amphis smans,vere, in the mean time, defeated t. But Philip preserved his connection,vith the Thebans, through the nlediation of his. The nevs that Philip had ta ken possession of Elatea first arrived at Athens late in the evening; the,vhole city,vas filled,vith consternation,vhich,vas so long in subsi ding, that vhen the people had asselnbled early the next morning, and the cryer had invited any person ~o offer his sentinlents as to the nlea. C ped to cruise in the streits of T~~rnlopylre;, that the cavalry and infantry should ll1arch, under their respective generals to Eleusis; and Cltap. In order to foil the Athenian politics, and to confirn1 his Gre cian allies, Philip sent to Thehes, as his ambassa dors, Alnyntas and Clcarchus, natives of 1.

From 1944 to 1964, domestic turkeys were subjected to intense selection for growth rate and body size. These correlated responses were due to negative genetic correlations between body size and fertility; eventually, these genetic correlations limited the extent to which the growth rate of turkeys could respond to selection. Genetic correlations may also limit the ability of natural populations to respond to selection in the wild and adapt to their environments. When two characteristics are genetically correlated, selection for one characteristic will produce a correlated response in the other characteristic. If greater milk yield is selected in this herd, what will be the effect on the percentage of butterfat For many quantitative characteristics, the relation between genotype and phenotype is complex because many genes and environmental factors influence a characteristic. Regression can be used to predict the value of one variable on the basis of the value of a correlated variable. Heritability is based on the variances present within a group of individuals, and an individual does not have heritability. The heritability of a characteristic varies among populations and among environments. Even if the heritability for a characteristic is high, the characteristic may still be altered by changes in the environment. Heritabilities provide no information about the nature of population differences in a characteristic. Genes influencing quantitative traits can also be located with the use of genomewide association studies. Cross two individuals that are each homozygous for different genes affecting the traits and then intercross the resulting F1 progeny to produce the F2. Determine what proportion of the F2 progeny resembles one of the original homozygotes in the P generation. This proportion should be (1/4)n, where n equals the number of loci with a segregating pair of alleles that affect the characteristic. It indicates that about 40% of the differences in blood pressure among African Americans in Detroit are due to additive genetic differences. It neither provides information about the heritability of blood pressure in other groups of people nor indicates anything about the nature of differences in blood pressure between African Americans in Detroit and people in other groups. Seed weight in a particular plant species is determined by pairs of alleles at two loci (a+a- and b+b-) that are additive and equal in their effects. Plants with genotype a-a- b-b- have seeds that average 1 g in weight, whereas plants with genotype a+a+ b+b+ have seeds that average 3. If the F1 plants are intercrossed, what are the expected seed weights and proportions of the F2 plants These two genotypes differ in four genes; so, if the genes have equal and additive effects, each gene difference contributes an additional 2. The cross between the two homozygous genotypes produces the F1 and F2 progeny shown in the table below. The F1 are heterozygous at both loci (a+a- b+b-) and possess two genes that contribute an additional 0. To calculate the means, we need to sum the values of x and y, which are shown in the last rows of columns A and D of the table. For the mean of parental height, x i 1640 = = 164 cm n 10 For the mean of the offspring height, x= yi 1681 = = 168. The sums of the these squared deviations are shown in the last row of columns C and F. For the regression, we need the covariance, which requires that we take the difference between each x value and its mean, multiply it by the difference between each y value and its mean [(xi - x)(yi - y), column G], and then sum these products (last row of column G). The variance is the sum of the squared deviations from the mean divided by n - 1, where n is the number of measurements: (x i - x)2 1944 sx 2 = = = 216 n -1 9 y= (yi - y)2 1750. To calculate the correlation coefficient and regression coefficient, we need the covariance: (x i - x)(yi - y) 1551 = = 172. The heights of parents and their offspring are measured for 10 families: Mean height of parents Mean height of offspring (cm) (cm) 150 152 157 163 188 193 165 163 160 152 142 157 170 183 183 175 152 163 173 180 From these data, determine a. In a regression of the mean phenotype of the offspring against the mean phenotype of the parents, the regression coefficient equals the narrow-sense heritability, which is 0.

Mutations in the Antennapedia gene, for example, cause legs to develop on the head of a fly in place of the antenna (Figure 22. Homeotic genes create addresses for the cells of particular segments, telling the cells where they are within the regions defined by the segmentation genes. When a homeotic gene is mutated, the address is wrong and cells in the segment develop as though they were somewhere else in the embryo. Homeotic genes in Drosophila are expressed after fertilization and are activated by specific concentrations of the proteins produced by the gap, pair-rule, and segmentpolarity genes. The homeotic gene Ultrabithorax (Ubx), for example, is activated when the concentration of Hunchback protein (a product of a gap gene) is within certain values. These concentrations exist only in the middle region of the embryo; so Ubx is expressed only in these segments. Homeoboxes are also present in segmentation genes and other genes that play a role in spatial development. In Drosophila, the bithorax complex comprises three genes, and the Antennapedia complex has five; all are located on the same chromosome (Figure 22. The genes that are expressed in the more-anterior segments are found at one end of the complex, whereas those expressed in the more-posterior end of the embryo are found at the other end of the complex (see Figure 22. The Antennapedia complex has five genes, and the bithorax complex has three genes. Homeobox Genes in Other Organisms After homeotic genes in Drosophila had been isolated and cloned, molecular geneticists set out to determine if similar genes exist in other animals; probes complementary to the homeobox of Drosophila genes were used to search for homologous genes that might play a role in the development of other animals. The search was hugely successful: homeobox-containing genes have been found in all animals, including nematodes, beetles, sea urchins, frogs, birds, and mammals. Genes with homeoboxes have even been discovered in fungi and plants, indicating that the homeobox arose early in the evolution of eukaryotes. One group of homeobox genes comprises the Hox genes, which include the homeotic complex of Drosophila described in the preceding section. In vertebrates, there are usually four clusters of Hox genes, each of which contains from 9 to 11 genes. Drosophila There are four clusters of Hox genes in mammals, each cluster containing from 9 to 11 genes. Mammal HoxC 1 HoxD 3 4 1 HoxA 1 HoxB 4 5 6 2 3 4 5 6 7 2 3 4 5 6 7 ple, the tunicate Oikopleura duiuca (a primitive relative of vertebrates) has 9 Hox genes, but the genes are scattered throughout the genome, unlike the clustered arrangement seen in most animals. The Hox genes of vertebrates also exhibit a relation between their order on the chromosome and the timing of their expression: genes at one end of the complex (those expressed at the anterior end) are expressed early in development, whereas genes at the other end (those expressed at the posterior end) are expressed later. If a Hox gene is experimentally moved to a new location within the Hoxgene complex, it is expressed in the appropriate tissue but the timing of its expression is altered, suggesting that the timing of gene expression is controlled by its physical location within the complex. Although the mechanism of this sequential control is not well understood, evidence suggests that, in mice, it is controlled by a progressive change in the methylation patterns of histone proteins, an epigenetic change that alters chromatin structure and affects transcription. The complexes are arranged so that genes with similar sequences lie in the same column. Developmental Genetics and Immunogenetics 621 Hox genes and their expression are often correlated with anatomical changes in animals, and Hox genes have been hypothesized to play an important role in the evolution of animals. For example, the lancet Branchiostoma (another primitive relative of vertebrates) has a simple body form and possesses only 14 Hox genes in a single cluster, whereas some fishes, with a much more complex body architecture, have as many as 48 Hox genes in seven clusters. The results of studies in fruit flies and other organisms reveal that this process is regulated by a large number of genes. The proteins of these genes then stimulate other genes, which in turn stimulate yet other genes in a cascade of control. In the course of development, successively smaller regions of the embryo are determined (Figure 22. In Drosophila, first, the major Single-celled embryo Egg-polarity genes axes and regions of the embryo are established by egg-polarity genes.