FUNDAMENTALS OF GENETICS: A SHORT COURSE

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Information about FUNDAMENTALS OF GENETICS: A SHORT COURSE

Published on January 9, 2019

Author: earshadshinichi

Source: slideshare.net

1. The Science of Heredity: Genetics Focus: Mendelian Genetics, Alternate Patterns of Heredity, Human Genetics, Chemical Basis of Heredity

2. Genetic Information Review of Terms: Genetics – branch of biology that deals with heredity and variation of organisms. Heredity – transmission of traits from parent to offspring Gene – basic unit of genetic information Alleles – the alternate form of a gene Locus – the specific site in a chromosome where alleles are located Chromosomes – storage units of genes Genome – the collection of genetic information

3. Chromosomes Chromosomes are made of DNA. Human body cells contain 46 chromosomes in 23 pairs – one of each pair inherited from each parent • Karyotype – a display of the whole sets of chromosomes of an organisms, arranged in decreasing size • Chromosome pairs 1 – 22 are called autosomes. The 23rd pair is called sex chromosomes: XX is female, XY is male.

4. Early Ideas On Genetics Aristotle contributions of traits from the male and female parents are very unequal The female thought to supply “matter” and the male supplies the “motion” The Blending Hypothesis (1800s) Offspring possess intermediate traits from the parents

5. Early Ideas On Genetics Scientists in the 19th Century, including Charles Darwin, believed that traits from parents are transmitted to their offspring by blood. Thus came the Blood Theory of Heredity. This concept gave rise to expressions, “bloodline” “blue-blood” and “blood relative”. Charles Darwin

6. The “Particulate” Hypothesis of Inheritance: the gene idea Gregor Mendel • An Austrian monk, 1866 • Worked in a monastery of St. Thomas in Brunn, Czech Rep • He was a teacher; in addition to that he was in charge of the monastery garden where he conducted his famous experiments

7. Who was Gregor Mendel? • Worked out with garden peas (Pisum sativum) as his “model system” • Tended the monastery garden • Grew peas and became interested in the traits that were expressed in different generations of peas Gregor Mendel

8. Important Terms in Mendelian Genetics a. Character – a heritable feature that varies among individuals, such as flower color b. Trait – each variant for a character, such as purple or white color for flowers c. True-breeding – plants that self-pollinate d. P generation – parental generation e. F1 – first filial generation f. F2 – second filial generation g. Hybrid – the result of the cross between two true- breeding plant with different traits

9. Why peas? 1. Peas have observable characters. 2. Peas are easy to grow. 3. They reproduce quickly. 4. They can reproduce hundreds of offspring. 5. They are capable of self- pollination. (self-fertilization) Pisum sativum

10. Mendel mechanically cross-pollinated the flowers.

11. The F1 generation offspring For each studied trait, all of the offspring had the characteristic of only one of the parent. The nature of the other parent seemed to have disappeared!

12. Factors as “Discrete Heritable Units” Dominant trait – the trait that showed in the F1 hybrids Recessive trait – the trait that did not manifest in the F1 hybrid Factors = genes (generic/ general); exists usually in pairs Allele = alternate form of a gene (specific) Example: Peas have genes for flower color; the alleles for flower color are Purple and White.

13. What were the F2 generation offspring look like? Mendel again this time cross-pollinated the F1 hybrids and produced both the parental traits in the F2 generation. Example: P generation: Purple x White F1 generation: All Purple F2 generation: 75% Purple 25% White

14. Mendel’s Principles of Heredity 1. Inheritance is determined by factors that are passed from generation to generation – today we call these factors genes. Factors exist in pairs. 2. The Principle of Dominance and Recessiveness Some alleles are dominant and some are recessive.

15. What really happened inside the pea cells?

16. Mendel’s Principles of Heredity 3. The Principle of Segregation During sex cells, or gamete, formation, the alleles for each gene separate from each other, so that each gamete carries only one allele for each gene. •Monohybrid cross •“Each trait separates.”

17. Mendel’s Principles of Heredity 4. The Principle of Independent Assortment The pairs of alleles segregate independently of one another during gamete formation. •Dihybrid cross •“Each character separates.”

18. Useful Genetic Vocabulary Genotype is the genetic composition of an organism (arbitrarily represented by letters) Phenotype is the physical trait or the trait expressed by the genotype PP, pp, and Pp are Genotypes. Purple and White are Phenotypes. Homozygous genes – when the same alleles pair; PP and pp Heterozygous genes – when different alleles pair; Pp

19. Useful Genetic Vocabulary Phenotypic Ratio: the ratio of phenotypes in a cross Example: Pp x Pp → 3 purple: 1 white PpTt x PpTt → 9 PT: 3 Ps: 3 wT: 1 ws Genotypic Ratio: the ratio of genotypes in a cross Example: Pp x Pp → 1PP : 2Pp : 1pp PpTt x PpTt →1: 2: 2: 1: 4: 1: 2: 2: 1

20. Punnett Square Diagram used to determine genetic crosses STEPS: 1. Determine the genotypes of the parent organisms 2. Write down your "cross" (mating) 3. Draw a p-square Parental phenotypes: Tall and Short Cross: TT  tt

21. The Test-Cross Suppose we have a “mystery” pea plant that has purple flowers. We cannot tell from its flower color if this plant is homozygous (PP) or heterozygous (Pp) because both genotypes result in the same purple phenotype. Breeding an organism of unknown genotype with a recessive homozygote is called a testcross.

22. Practice Problem In Medelian Genetics “Put on your thinking caps!”

23. 1. A woman has a rare abnormality of the eyelids called ptosis, which makes it impossible for her to open her eyes completely. The condition has been found to depend on a single dominant gene (P). The woman’s father had ptosis, but her mother had normal eyelids. Her father’s mother had normal eyelids. A. What are the probable genotypes of the woman, her father and her mother? B. What proportion of her children will be expected to have ptosis if she marries a man with normal eyelids? Monohybrid Cross

24. 1. Tall (T) is dominant over short(t). Round seed plants (R) is dominant over wrinkled ones (r). If a heterozygous tall garden pea plant with heterozygous round seeds is crossed with a short garden pea plant with wrinkled seeds, A. What are the genotypes of the parent peas? B. What is the chance that one of their offspring is tall with wrinkled seeds? Dihybrid Cross

25. Definitely “Non-Mendelian” Two different types of complications: 1. Genotypic ratios follow Mendel's laws, but phenotypes do not. Somehow the underlying genotypic ratios are hidden 2. Mendel’s laws do not apply. Both genotypes and phenotypes are not following Mendel’s laws.

26. Phenotypic Ratios do not dollow Mendel’s observation Incomplete dominance Codominance Multiple Alleles Polygenic traits Epistasis Pleiotropy Penetrance Expressivity Phenocopies Genetic Heterogeneity Lethal genotypes Influenced by Environment Sex-influenced

27. Alternate Forms of Heredity Incomplete Dominance The trait exhibited by the offspring is intermediate or in- between the parents’ traits Ex: When white 4 o’clock plants are crossed with red ones, pink flowers are produced.

28. Incomplete Dominance in human hypercholesterolemia GENOTYPES: HH Homozygous for ability to make LDL receptors Hh Heterozygous hh Homozygous for inability to make LDL receptors PHENOTYPES: LDL LDL receptor Cell Normal Mild disease Severe disease

29. Codominance • It is when either allele masks the other so that effects of both alleles are observed in heterozygote without blending. • Both of the traits of the parents are manifested in the offspring. Erminette (speckled) hen

30. Multiple Alleles •Many genes exist in several different forms and are therefore said to have multiple alleles. •A gene with more than two alleles is said to have multiple alleles.

31. Pleiotropy One allele/gene has many phenotypic effects. Example: Allele: S S’ Gene Product: Hemoglobin A Hemoglobin S Cell Shape: Round Sickled under low O2 tension Response to Malaria: Susceptible Resistant in SS’ genotype Sickle-shaped and Normal RBC

32. What causes the sickling of the RBCs? A mutation happened in the gene coding for hemoglobin. The middle base of the codon for Glutamic acid (GAG) is changed into U. The codon now translates to Valine.

33. Selection Advantage in Sickle-Celled Pleiotropic effects of sickle cell in tropical Africa: 1. Homozygotes – succumb to malaria 2. Recessive – die of sickle cell anemia 3. Heterozygotes – relatively free of both

34. Q&A Q: What blood type is the universal blood recipient?

35. ABO Human Blood System • The human blood type (ABO blood system) exhibits both codominance and multiple alleles. • Alleles for A and B are dominant over O. • Yet, A and B are codominant.

36. Codominance in Blood Type Allele for A is codominant with the allele for B. The allele for O is recessive. IA = IB > i

37. Phenotype Genotype Gene Product Antibodies Present Type A IAIA or IAi Antigen A Anti-B Type B IBIB or IBi Antigen B Anti-A Type AB IAIB Antigen A and Antigen B Neither Anti-A nor Anti-B Type O ii none Anti-A and Anti-B

38. Antigens on Red Blood Cells

39. Polygenes or Multiple Genes (Polygenic traits) Many traits are produced by the interaction of several genes. Quantitative Characters Traits are controlled by 2 or more genes are said to be polygenic traits. Example: Pigment in fruit flies eyes and human skin color, height, intelligence and weight Normal distribution

40. Polygenes (Polygenic Traits) In humans, the skin color inheritance is governed by polygenic interactions. The table below shows what genotype controls a particular phenotype. GENOTYPE PHENOTYPE AABB Black AABb; AaBB Dark Brown AAbb; aaBB; AaBb Medium Brown Aabb; aaBb Light Brown aabb Fair

41. Epistasis is a form of gene interaction in which one gene masks the phenotypic expression of another. An allele of one gene masks the expression of alleles of another gene and expresses its own phenotype instead. The alleles that are masking the effect are called epistatic alleles. The alleles whose effect is being masked are called the hypostatic alleles. There are no new phenotypes produced by this type of gene interaction. Epistasis

42. Epistasis Fur color in Labrador Retrievers is controlled by two separate genes. Fur color is a polygenic trait. 1. Gene 1: Represented by B Controls color (B → black; b → brown) 2. Gene 2: Represented by E Controls expression of B If ee is present, gold color fur manifests. If E_ is present, simple dominance follows.

43. Lethal Genotypes • Certain combinations of genotypes (alleles) are fatal to an organism having such genotypic (allelic) combination. • Majority of these organisms die just before being born or formed. Example: In Manx cat, the homozygous dominant combination of alleles for tailless is lethal. M = tailless; m = tail

44. Genetic Heterogeneity More than one gene producing the same phenotype, associated more with disorders. It is thought to be caused by a mutation to a particular gene for a phenotype in multiple alleles or in completely unrelated genes. Example: Autism Cystic fibrosis Retinitis pigmentosa

45. Nature and Nurture: The Environmental Impact on Phenotype Phenotype is dependent upon the presence of a specific environment. Multifactorial Traits For humans, nutrition influences height, exercise alters build, sun-tanning darkens the skin, and experience improves performance on intelligence tests. Even identical twins, who are genetic equals, accumulate phenotypic differences as a result of their unique experiences.

46. Hydrangea pink and blue flowers in soils with free Aluminum. Himalayan hares raised in different temperatures.

47. Autosomal Traits Traits that are coded in genes found in the autosomes. Autosomal Dominant: 1. Huntington’s Disease - progressive dementia with onset in adulthood 2. Marfan’s Syndrome - aortic aneurysms and faulty scaffolding in connective tissue 3. Polydactyly – extra fingers in the hands 4. Familial Hypercholesterolemia

48. Autosomal Traits Autosomal Recessive: 1. Cystic Fibrosis – defective Cl- channels resulting to excessive viscoid mucus secretions 2. Tay-Sachs Disease – accumulation of lipids in the CNS 3. Albinism 4. Phenylketonuria – build up of phenylalanine in body tissues and the CNS 5. Thalassemia

49. Pedigree

50. Traits Affected by Sex Traits that are coded by autosomal chromosomes but greatly affect members of either sex. 1. Sex-limited Traits Lactation in females; Beard in males 2. Sex-influenced Traits Pattern baldness; Development of body parts

51. Sex-linked Traits Genes that are located in the X or Y chromosomes produce a trait linked to being a male or female. Sex-linked recessive: Hemophilia, R-G colorblindness Sex-linked dominant: Fragile-X syndrome (mental retardation)

52. Most frequent chromosomal anomalies in liveborn Autosomal Trisomy Down syndrome (trisomy 21: 47, X_+21) Edwards syndrome (trisomy 18: 47, X_+18) Patau syndrome (trisomy 13: 47, X_+13) Non-disjunction in Sex Chromosomes Turner syndrome 45,X Klinefelter syndrome 47,XXY All chromosomes Triploidy (69 chromosomes) trisomy 13► trisomy 18▲

53. Most frequent chromosomal anomalies in liveborn Non-disjunction in Sex Chromosomes Turner syndrome 45,X Klinefelter syndrome 47,XXY All chromosomes Triploidy (69 chromosomes) ◄ Klinefelter’s Turner’s ►

54. Ploidy Ploidy is the number of chromosomes or sets of chromosomes in an organism. 1. Euploidy – state when a cell/organism has one or more than one set of chromosomes 2. Aneuploidy – state when a cell/organism has one or more than one chromosome is missing in a set Euploidy: 1. Mono-, Di-, Poly- 2. Autopolyploidy 3. Allopolyploidy Aneuploidy: 1. Hypo-, Hyper- 2. Mono-, Trisomy 3. Nulli-, Tetra-

55. 1. Pea plants were particularly well suited for use in Mendelʹs breeding experiments for all of the following reasons except that __________. A. peas show easily observed variations in a number of characters, such as pea shape and flower color. B. it is possible to control matings between different pea plants. C. it is possible to obtain large numbers of progeny from any given cross. D. peas have an unusually long generation time.

56. 2. What is the difference between a monohybrid cross and a dihybrid cross? A. A monohybrid cross involves a single parent, whereas a dihybrid cross involves two parents. B. A monohybrid cross produces a single progeny, whereas a dihybrid cross produces two progeny. C. A dihybrid cross involves organisms that are heterozygous for two characters and a monohybrid only one. D. A monohybrid cross is performed for one generation, whereas a dihybrid cross is performed for two generations.

57. 3. What was the most significant conclusion that Gregor Mendel drew from his experiments with pea plants? A. There is considerable genetic variation in garden peas. B. Traits are inherited in discrete units, and are not the results of ʺblending.ʺ C. Recessive genes occur more frequently in the F1 than do dominant ones. D. Genes are composed of DNA

58. 4. How many unique gametes could be produced through independent assortment by an individual with the genotype AaBbCCDdEE? A. 4 B. 8 C. 16 D. 32

59. 5. When crossing an organism that is homozygous recessive for a single trait with a heterozygote, what is the chance of producing an offspring with the homozygous recessive phenotype? A. 0% B. 25% C. 50% D. 75%

60. 6. Mendelʹs second law of independent assortment has its basis in which of the following events of meiosis I? A. Synapsis of homologous chromosomes B. Crossing over C. Alignment of tetrads at the equator D. Separation of homologs at anaphase

61. 7. In a cross AaBbCc × AaBbCc, what is the probability of producing the genotype AABBCC? A. 1/8 B. 1/16 C. 1/32 D. 1/64

62. 8. In snapdragons, heterozygotes for one of the genes have pink flowers, whereas homozygotes have red or white flowers. When plants with red flowers are crossed with plants with white flowers, what proportion of the offspring will have pink flowers? A. 25% B. 50% C. 75% D. 100%

63. 9. In cattle, roan coat color (mixed red and white hairs) occurs in the heterozygous (Rr) offspring of red (RR) and white (rr) homozygotes. Which of the following crosses would produce offspring in the ratio of 1 red : 2 roan : 1 white? A. red × white B. roan × roan C. white × roan D. red × roan

64. 10. Huntingtonʹs disease is a dominant condition with late age of onset in humans. If one parent has the disease, what is the probability that his or her child will have the disease? A. 1 B. ¾ C. ½ D. ¼

65. 11. A human cell containing 22 autosomes and a Y chromosome is ________. A. a sperm. B. an egg. C. a zygote. D. a somatic cell of a male.

66. 12. Phenylketonuria (PKU) is an inherited disease caused by a recessive allele. If a woman and her husband, who are both carriers, decided to have children. What is the probability that the next child is PKU inflicted? A. 0% B. 25% C. 50% D. 75%

67. 13. Which refers to the organism’s physical appearance or observable traits? A. Phenotype B. Genotype C. Homozygous D. Heterozygous

68. 14. A man who has hemophilia married a woman who is a carrier. What proportion of the male offspring will have the disease? A. 0% B. 25% C. 50% D. 100%

69. 15. Which of the following shows aneuploidy? A. 2N B. 4N C. 2N+1 D. N

70. 16. A pedigree analysis for a given disorderʹs occurrence in a family shows that, although both parents of an affected child are normal, each of the parents has had affected relatives with the same condition. The disorder is then which of the following? A. Recessive B. Dominant C. Incompletely dominant D. Lethal

71. 17. Cystic fibrosis (CF) is a Mendelian disorder in the human population that is inherited as a recessive. Two normal parents have two children with CF. The probability of their next child being normal for this characteristic is which of the following? A. 0 B. 1/2 C. 1/4 D. 3/4

72. 18. When a disease is said to have a multifactorial basis, it means that A. both genetic and environmental factors contribute to the disease. B. it is caused by a gene with a large number of alleles. C. it affects a large number of people. D. it has many different symptoms.

73. 19. A woman has six sons. The chance that her next child will be a daughter is A. 1. B. 0. C. 1/2. D. 1/6.

74. 20. Which describes the ABO blood group system? A. Incomplete dominance B. Multiple alleles C. Pleiotropy D. Epistasis

75. 21. Which of the following is an example of polygenic inheritance? A. Pink flowers in snapdragons B. Huntingtonʹs disease in humans C. White and purple flower color in peas D. Skin pigmentation in humans

76. 22. Which describes the ability of a single gene to have multiple phenotypic effects? A. Incomplete dominance B. Multiple alleles C. Pleiotropy D. Epistasis

77. 23. The Principle of Segregation is manifested during which process? A. Prophase I B. Crossing-over C. Anaphase II D. S phase

78. 24. When a woman has only one X chromosome in each of her cell in the body, the condition is known as _______ A. Turner’s Syndrome B. Klinefelter’s Syndrome C. Triple X Syndrome D. Marfan’s Syndrome

79. 25. Which of the following disorders is a direct result of nondisjunction? A. sickle cell disease B. Turner’s syndrome C. Huntington’s disease D. cystic fibrosis

80. 26. Which symbol usually represents a normal male in a genetic pedigree? A. Shaded circle B. Unshaded circle C. Shaded square D. Unshaded square

81. 27. Which of the following disorders can be observed in a human karyotype? A. Colorblindness B. Trisomy 21 C. Cystic fibrosis D. Sickle cell disease

82. 28. The human genome consists of approximately how many DNA base pairs? A. 30,000 B. 3,000,000 C. 300,000,000 D. 3,000,000,000

83. 29. Malaria is a disease caused by a ____________. A. gene mutation. B. defect in red blood cells. C. bacterium found in water. D. parasite carried by mosquitoes.

84. 30. A normal human diploid zygote contains A. 23 chromosomes. B. 44 chromosomes. C. 46 chromosomes. D. XXY chromosomes

85. Practice Problem in Non-Mendelian Genetics “Put on your thinking caps!”

86. 1. In your garden, you have some red flowers and some yellow flowers. You decide to cross a pure-breeding red flower with a pure- breeding yellow flower, and it results in all orange flowers. A. Which pattern of inheritance does this show? B. What is the phenotypic ratio of this cross? Alternate Pattern of Inheritance

87. 3. What are the possible genotypes of the parents of a child with type AB blood? What is this mode of inheritance? 4. You discover a new mammal species in the jungles of the Amazon. Some of the animals have purple fur and some have green fur, but when you cross a purple animal with a green animal, you get offspring that have both purple and green hairs intermingled with each other. What pattern of inheritance does this show?

88. GENOTYPE PHENOTYPE AABB Black AABb; AaBB Dark Brown AAbb; aaBB; AaBb Medium Brown Aabb; aaBb Light Brown aabb Fair What are the possible traits of the offspring of the crosses between: a) Light Brown x Fair ? b) Dark Brown x Aabb genotype?

89. 5. You have decided to cross your golden retriever (bbee) with the neighbor’s chocolate retriever (bbEe). What color of pups will they have? 6. What are the possible blood types of a marriage between a type O woman and a type AB man?

90. 7. Hemophilia is a sex-linked disease. Homozygous recessive genes are needed on the X-chromosomes for the disease to be expressed. A man who does not have this disease and a woman who is a carrier decide to have children. a. What are the genotypes of the man and the woman? b.What is the probability of a son having haemophilia?

91. In an epistatic gene interaction, squash fruit color is controlled by two genes. Gene 1 is represented by a W. Gene 2 is represented by a G. The genotypes and the phenotypes are the following: GENOTYPE PHENOTYPE W_G_ white wwG_ orange wwgg yellow W_gg yellow 1. Which allele is epistatic in squash color? 2. What color are the offspring of a cross between a orange squash (wwGg) with a white squash (WwGg).

92. 1. In a case of disputed paternity you, as the expert witness, were told the mother has type A blood, the child has type 0, and the alleged father has type B blood. How would you respond to the following statements? a. The attorney for the alleged father asks ''since the mother has type A blood, the type O blood of the child must have come from the father, and since my client has type B blood, he obviously could not have fathered the child. b. Her attorney states, "Further tests reveal that this man is heterozygous and therefore, he must be the father".

93. POST-MENDELIAN TIME • Mendel’s findings on the transmission of hereditary information were not widely recognized at the time • This was partly due to the strong divisions that existed among scientific disciplines then, which meant that the work of a botanist was not likely to be noticed by zoologists or by medical doctors. • Over the next few decades, however, scientists began to recognize the many similarities among cellular processes in bacterial, plant, animal, and human cells. • Today, Mendel’s work is recognized as the foundation of modern genetics.

94. Isolating The Material Of Heredity Friedrich Miescher (1869) Only four years after Mendel’s presentation in Brunn, and less than 300 km away, this young Swiss physician and scientist isolated a substance he called “NUCLEIN” from the nuclei of white blood cells. He worked in a hospital treating wounded soldiers.

95. Isolating The Material Of Heredity Friedrich Miescher (1869) Miescher, determined that nuclein was made up of an acidic portion (which he termed “NUCLEIC ACID”) and an alkaline portion (which was later shown to be protein).

96. The Components Of Nucleic Acid Phoebus Levene (1920s) He isolated two types of nucleic acids that could be distinguished by the different sugars involved in their composition. He named the nucleic acids according to the type of sugar present. Can you guess the names of nucleic acid Levene has described?

97. The Components Of Nucleic Acid Phoebus Levene (1920s) One acid contained the five- carbon sugar ribose, so Levene called it “RIBOSE NUCLEIC ACID” (ribonucleic acid or RNA) and the other one, deoxyribose, calling the nucleic acid containing this sugar “DEOXYRIBOSE NUCLEIC ACID” (deoxyribonucleic acid or DNA).

98. THE COMPONENTS OF NUCLEIC ACID The structure of (A) ribose, found in RNA, and (B) deoxyribose, found in DNA. In ribose, the 2′ carbon is bonded to a hydroxyl group (OH). In deoxyribose, this carbon is bonded to a single hydrogen molecule (H).

99. THE CHEMICAL BASIS OF HEREDITY

100. POST-MENDELIAN TIME • Mendel’s findings on the transmission of hereditary information were not widely recognized at the time • This was partly due to the strong divisions that existed among scientific disciplines then, which meant that the work of a botanist was not likely to be noticed by zoologists or by medical doctors. • Over the next few decades, however, scientists began to recognize the many similarities among cellular processes in bacterial, plant, animal, and human cells. • Today, Mendel’s work is recognized as the foundation of modern genetics.

101. ISOLATING THE MATERIAL OF HEREDITY Friedrich Miescher (1869) Only four years after Mendel’s presentation in Brunn, and less than 300 km away, this young Swiss physician and scientist isolated a substance he called “NUCLEIN” from the nuclei of white blood cells. He worked in a hospital treating wounded soldiers.

102. ISOLATING THE MATERIAL OF HEREDITY Friedrich Miescher (1869) Miescher, determined that nuclein was made up of an acidic portion (which he termed “NUCLEIC ACID”) and an alkaline portion (which was later shown to be protein).

103. THE COMPONENTS OF NUCLEIC ACID Phoebus Levene (1920s) He isolated two types of nucleic acids that could be distinguished by the different sugars involved in their composition. He named the nucleic acids according to the type of sugar present. Can you guess the names of nucleic acid Levene has described?

104. THE COMPONENTS OF NUCLEIC ACID Phoebus Levene (1920s) One acid contained the five- carbon sugar ribose, so Levene called it “RIBOSE NUCLEIC ACID” (ribonucleic acid or RNA). The other acid contained a previously unknown five-carbon sugar molecule. Since this sugar was similar in structure to ribose but lacked one oxygen molecule, Levene called it deoyribose, calling the nucleic acid containing this sugar

105. THE COMPONENTS OF NUCLEIC ACID The structure of (A) ribose, found in RNA, and (B) deoxyribose, found in DNA. In ribose, the 2′ carbon is bonded to a hydroxyl group

106. THE COMPONENTS OF NUCLEIC ACID • During the period when Levene was conducting his studies on nucleic acids, other experimenters demonstrated that Mendel’s factors of inheritance were associated with the nuclein substance first isolated by Miescher. • By that time, nuclein had been shown to be made up of individual structures known as CHROMOSOMES, strand-like complexes of nucleic acids and protein tightly bound together.

107. THE COMPONENTS OF NUCLEIC ACID NUCLEOTIDE is the basic unit of nucleic acids. Both DNA and RNA contain a combination of four different nucleotides. Each nucleotide is composed of a FIVE-CARBON SUGAR, a PHOSPHATE GROUP, and one of the four NITROGEN-CONTAINING BASES (NITROGENOUS BASE).

108. THE COMPONENTS OF A NUCLEIC ACID The four Nitrogenous bases found in the DNA are the following: Purine Base Pyrimidine Base Adenine (A) Thymine (T) Guanine (G) Cytosine (C)

109. THE COMPONENTS OF A NUCLEIC ACID The general structure of a nucleotide. In DNA, the sugar is deoxyribose, and the nitrogenous base is one of the following: adenine (A), guanine (G), cytosine (C), or

110. The DNA strand is composed of repeating units of nucleotide joined together, as suggested by Levene.

111. TURNING POINT: LEVENE’S MISTAKES • The results of Levene’s work led him to conclude incorrectly that nucleic acids contained equal amounts of each of these nucleotides. • He suggested that DNA and RNA were made up of long chains in which the nucleotides appeared over and over again in the same order; for example, ACTGACTGACTG and so on. • It was generally accepted that DNA could be a structural component of hereditary material, but scientists thought the primary instructions for inherited traits must lie in the proteins that are also found in chromosomes.

112. IDENTIFYING THE SUBSTANCE OF GENES So, is it really the proteins that have the primary instructions for inherited traits? Or is it the gene? The very first evidence that provided the answer was the investigation on how bacteria make people sick.

113. GRIFFITH’S EXPERIMENT In 1928, the British scientist Frederick Griffith was trying to figure out how bacteria make people sick. More specifically, Griffith wanted to learn how certain types of bacteria produce the serious lung disease known as pneumonia.

114. TRANSFORMING PRINCIPLE Griffith showed that when a heat- killed, pathogenic (disease-causing) strain of the bacterium Streptococcus pneumoniae was added to a suspension containing a non-pathogenic strain, the non-pathogenic strain was somehow transformed to become pathogenic.

115. GRIFFITH’S EXPERIMENT: BACTERIAL TRANSFORMATION

116. GRIFFITH’S EXPERIMENT: BACTERIAL TRANSFORMATION

117. GRIFFITH’S EXPERIMENT: BACTERIAL TRANSFORMATION

118. GRIFFITH’S EXPERIMENT: BACTERIAL TRANSFORMATION

119. MOUNTING EVIDENCE FOR THE ROLE OF DNA IN HEREDITY • One important piece of evidence that DNA was, in fact, the material of heredity came in 1944, when the team of Oswald Avery, Colin MacLeod, and Maclyn McCarty published the results of their experiments with bacteria. • Repeated Griffith’s experiment but this time they used the DNA of the bacteria. They also used RNA but to no effect. • Others were still skeptic; others believed but maintained that while DNA might be an agent of heredity in bacteria, prokaryotes were not a reliable model for genetic mechanisms in more complex organisms.

120. BACTERIAL VIRUSES What role did bacterial viruses play in identifying genetic material? •Scientists are skeptical kind of persons. •The most important of the experiments relating to the discovery made by Avery’s team was performed in 1952 by two American scientists, Alfred Hershey and Martha Chase. They collaborated in studying viruses—tiny, nonliving particles that can infect living cells.

121. BACTERIOPHAGES • A bacteriophage is a kind of virus that infects bacteria. When a bacteriophage enters a bacterium, it attaches to the surface of the bacterial cell and injects its genetic information into it. • Looking somewhat like space capsules, these T2 phages use leg-like structures to bind to the cell wall of a bacterium.

122. • T4 Bacteriophage is a kind of virus that infects a bacterium of the Escherichia coli • It injects its DNA to its host cell and hijacks the cell machinery.

123. THE HERSHEY-CHASE EXPERIMENT • Hershey and Chase studied a bacteriophage that was composed of a DNA core and a protein coat. • They wanted to determine which part of the virus—the protein coat or the DNA core— entered the bacterial cell. Their results would either support or disprove Avery’s finding that genes were made of DNA.

124. THE HERSHEY-CHASE EXPERIMENT • The pair grew viruses in cultures containing radioactive isotopes of phosphorus-32 ( 32 P) and sulfur-35 ( 35 S). • These radioactive substances could be used as markers, enabling the scientists to tell which molecules actually entered the bacteria, carrying the genetic information of the virus. • If they found radioactivity from 35 S in the bacteria, it would mean that the virus’s protein coat had been injected into the bacteria. • If they found 32 P, then the DNA core had been injected.

125. THE ROLE OF DNA What is the role of DNA in heredity? The DNA that makes up genes must be capable of storing, copying, and transmitting the genetic information in a cell.

126. THE ROLE OF DNA Storing Information The foremost job of DNA, as the molecule of heredity, is to store information.

127. THE ROLE OF DNA Copying Information Before a cell divides, it must make a complete copy of every one of its genes. To many scientists, the most puzzling aspect of DNA was how it could be copied. The solution to this and other puzzles had to wait until the structure of the DNA molecule became known. Within a few weeks of this discovery, a copying mechanism for the genetic material was put forward.

128. THE ROLE OF DNA Transmitting Information As Mendel’s work had shown, genes are transmitted from one generation to the next. Therefore, DNA molecules must be carefully sorted and passed along during cell division. Such careful sorting is especially important during the formation of reproductive cells in meiosis.

129. THE STRUCTURE OF DNA

130. THE STRUCTURE OF DNA THINK ABOUT IT It’s one thing to say that the molecule called DNA carries genetic information, but it would be quite another thing to explain how it could do this. DNA must not only specify how to assemble proteins, but how genes can be replicated and inherited. DNA has to be a very special molecule, and it’s got to have a very special structure.

131. THE STRUCTURE OF DNA • Deoxyribonucleic acid, or DNA, is a unique molecule indeed. • DNA is a nucleic acid made up of nucleotides joined into long strands or chains by covalent bonds.

132. THE STRUCTURE OF DNA Nucleic Acids and Nucleotides • Nucleic acids are long, slightly acidic molecules originally identified in cell nuclei. • Nucleotides are the building blocks of nucleic acids.

133. THE STRUCTURE OF DNA Nitrogenous Bases and Covalent Bonds • Nitrogenous bases, simply put, are bases that contain nitrogen. • Remember A, T, C, and G? • The nucleotides in a strand of DNA are joined by covalent bonds formed between the sugar of one nucleotide and the phosphate group of the next.

134. THE STRUCTURE OF DNA Covalent Bond • Chemical bonding between two non- metals. • Where is it found in the DNA? • Between the sugar of one nucleotide and the phosphate group of the next

135. THE STRUCTURE OF DNA Nitrogenous Bases and Covalent Bonds • The nitrogenous bases stick out sideways from the nucleotide chain. • The nucleotides can be joined together in any order, meaning that any sequence of bases is possible. These bases have a chemical structure that makes them especially good at absorbing ultraviolet (UV) light. • In fact, we can determine the amount of DNA in a solution by measuring the amount of light it absorbs at a wavelength of 260 nanometers (nm), which is in the UV region of the electromagnetic spectrum.

136. SOLVING THE STRUCTURE OF THE DNA What clues helped scientists solve the structure of DNA? •Knowing that DNA is made from long chains of nucleotides was only the beginning of understanding the structure of this molecule. The next step required an understanding of the way in which those chains are arranged in three dimensions.

137. CHARGAFF’S RULE • Years earlier, Erwin Chargaff, an Austrian-American biochemist, had discovered that the percentages of adenine [A] and thymine [T] bases are almost equal in any sample of DNA. • The observation that [A] = [T] and [G] = [C] became known as “Chargaff’s rule.”

138. In 1949, Erwin Chargaff discovered that the relative amounts of A and T, and of G and C, are almost always equal. The table shows a portion of the data that Chargaff collected. • Which organism has the highest percentage of adenine? If a species has 35 percent adenine in its DNA, what is the percentage of the other three bases?

139. FRANKLIN’S X-RAYS •In the early 1950s, the British scientist Rosalind Franklin began to study DNA. Franklin used a technique called X-ray diffraction to get information about the structure of the DNA molecule.

140. FRANKLIN’S X-RAYS • First, she purified a large amount of DNA, then stretched the DNA fibers in a thin glass tube so that most of the strands were parallel. • Next, she aimed a powerful X-ray beam at the concentrated DNA samples and recorded the scattering pattern of the X-rays on film.

141. FRANKLIN’S X-RAYS What did Franklin’s work suggest? •The X-shaped pattern shows that the strands in DNA are twisted around each other like the coils of a spring, a shape known as a helix. The angle of the X suggests that there are two strands in the structure. Other clues suggest that the nitrogenous bases are near the center of the DNA molecule.

142. THE WORK OF WATSON AND CRICK •While Franklin was continuing her research, James Watson, an American biologist, and Francis Crick, a British physicist, were also trying to understand the structure of DNA. •They built three-dimensional models of the molecule that were made of cardboard and wire. They twisted and stretched the models in various ways, but their best efforts did nothing to explain DNA’s properties.

143. Watson & Crick (1953)

144. The clues in Franklin’s X-ray pattern enabled Watson and Crick to build a model that explained the specific structure and properties of DNA.

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