Inheritance Biology - MLT Sem III PDF

INHERITANCE BIOLOGY Gregor Johann Mendel ▪ His parents were farmers in Moravia ▪ A rural upbringing taught him plant and animal husbandry and inspired an interest in nature ▪ At the age of 21, entered a Catholic monastery in the city of Brünn ▪ In 1847 he was ordained a priest, adopting...

INHERITANCE BIOLOGY Gregor Johann Mendel ▪ His parents were farmers in Moravia ▪ A rural upbringing taught him plant and animal husbandry and inspired an interest in nature ▪ At the age of 21, entered a Catholic monastery in the city of Brünn ▪ In 1847 he was ordained a priest, adopting the clerical name Gregor ▪ After returning to Brünn, he resumed his life as a teaching monk and began the genetic experiments that eventually made him famous Gregor Johann Mendel (1822–1884) 2 Mendel’s Experimental Organism - The Garden Pea One reason for Mendel’s success is that he chose his experimental material astutely ▪ Mendel performed experiments with several species of garden plants, and he even tried some experiments with honeybees ▪ His greatest success, however, was with peas ▪ He completed his experiments with peas in 1864 Pisum sativum 3 Why Mendel Choose Garden Pea as Experimental Material ? 1. The garden pea, Pisum sativum, is easily grown in experimental gardens or in pots in a greenhouse 2. Pea flowers contain both male and female organs. The male organs, called anthers, produce sperm-containing pollen, and the female organ, called the ovary, produces eggs 3. The petals of the flower close down tightly, preventing pollen grains from entering or leaving. This enforces a system of self- fertilization, in which male and female gametes from the same flower unite with each other to produce seeds. As a result, individual pea strains are highly inbred, displaying little if any genetic variation from one generation to the next. Because of this uniformity, we say that such strains are true-breeding 4 Self Fertilization & True breeding 5 Mendel obtained many different true-breeding varieties of peas, each distinguished by a particular characteristic 6 Monohybrid Crosses: The Principles of Dominance And Segregation Mendel cross- fertilized—or, simply, crossed— tall and dwarf pea plants to investigate how height was inherited Clearly, the hybrids that he had made by crossing tall and dwarf varieties had the ability to produce dwarf progeny even though they themselves were tall. 7 ▪ Mendel inferred that these hybrids carried a latent genetic factor for dwarfness, one that was masked by the expression of another factor for tallness. ▪ He said that the latent factor was recessive and that the expressed factor was dominant. ▪ He also inferred that these recessive and dominant factors separated from each other when the hybrid plants reproduced. 8  Monohybrid Crosses: The Principles of Dominance And Segregation ▪ Mendel performed similar experiments to study the inheritance of six other traits: seed texture, seed color, pod shape, pod color, flower color, and flower position. ▪ In each experiment—called a monohybrid cross because a single trait was being studied—Mendel found that these progeny consistently appeared in a ratio of 3:1. 9 Important Conclusions of Mendel ▪ Heritable factor - Gene ▪ Forms of heritable factor – Allele ▪ Genes come in pair – Homozygous vs. Heterozygous 10  Gene & Allele ▪ Each trait that Mendel studied seemed to be controlled by a heritable factor that existed in two forms, one dominant, the other recessive. ▪ These factors are now called genes, a word coined by the Danish plant breeder Wilhelm Johannsen in 1909; their dominant and recessive forms are called alleles—from the Greek word meaning “of one another.” Alleles are alternate forms of a gene 11  Genes Come In Pairs ▪ Mendel proposed that each of the parental strains that he used in his experiments carried two identical copies of a gene—in modern terminology, they are diploid and homozygous. ▪ During the production of gametes, Mendel proposed that these two copies are reduced to one; that is, the gametes that emerge from meiosis carry a single copy of a gene—in modern terminology, they are haploid. ▪ Mendel recognized that the diploid gene number would be restored when sperm and egg unite to form a zygote. 12 ▪ Furthermore, he understood that if the sperm and egg came from genetically different plants—as they did in his crosses—the hybrid zygote would inherit two different alleles, one from the mother and one from the father. Such an offspring is said to be heterozygous. ▪ Mendel realized that the different alleles that are present in a heterozygote must coexist even though one is dominant and the other recessive, and that each of these alleles would have an equal chance of entering a gamete when the heterozygote reproduces. ▪ Furthermore, he realized that random fertilizations with a mixed population of gametes—half carrying the dominant allele and half carrying the recessive allele—would produce some zygotes in which both alleles were recessive. ▪ Thus, he could explain the reappearance of the recessive characteristic in the progeny of the hybrid plants. 13  Symbolic Representation Mendel used symbols to represent the hereditary factors that he postulated— a methodological breakthrough The symbols stand for genes (or, more precisely, for their alleles) 14  Symbolic Representation The allelic constitution of each strain is said to be its genotype The physical appearance of each strain—the tall or dwarf characteristic—is said to be its phenotype 15 The Principle of Dominance In a heterozygote, one allele may conceal the presence of another - This principle is a statement about genetic function - Some alleles evidently control the phenotype even when they are present in a single copy 16 The Principle of Segregation In a heterozygote, two different alleles segregate from each other during the formation of gametes - This principle is a statement about genetic transmission - An allele is transmitted faithfully to the next generation, even if it was present with a different allele in a heterozygote - The biological basis for this phenomenon is the pairing and subsequent separation of homologous chromosomes during meiosis 17  DIHYBRID CROSSES: THE PRINCIPLE OF INDEPENDENT ASSORTMENT Mendel crossed plants that produced yellow, round seeds with plants that produced green, wrinkled seeds. The purpose of the experiments was to see if the two seed traits, color and texture, were inherited independently 18 Dihybrid Cross- Using Mendel’s Method 19  The Principle of Segregation predicts that the F1 hybrids will produce four different gametic genotypes: (1) G W, (2) G w, (3) g W, and (4) g w 20 Dihybrid Crosses: The Principle of Independent Assortment This analysis is predicated on two assumptions: 1. Each gene segregates its alleles 2. These segregations are independent of each other The second assumption implies that there is no connection or linkage between the segregation events of the two genes. 21  Dihybrid Crosses: The Principle of Independent Assortment The alleles of different genes segregate, or assort independently of each other - This principle is another rule of genetic transmission, on the behavior of different pairs of chromosomes during meiosis - However, not all genes abide by the Principle of Independent Assortment 22  Summary ❑ Mendel’s research led him to formulate three principles of inheritance… 1. The alleles of a gene are either dominant or recessive 2. Different alleles of a gene segregate from each other during the formation of gametes 3. The alleles of different genes assort independently 23 Genetics—the study of heredity Cytology—the study of cells ▪ The discovery that genes play a role in the determination of sex emerged from a fusion between two previously distinct scientific disciplines, genetics—the study of heredity—and cytology—the study of cells ▪ Early in the twentieth century, these disciplines were brought together through a friendship between two remarkable American scientists, Thomas Hunt Morgan and Edmund Beecher Wilson 24 ▪ As the cytologist, Wilson was interested in the behavior of chromosomes. ▪ One of the first to investigate differences in the chromosomes of the two sexes ▪ Showed that these differences were confined to a special pair of chromosomes called sex chromosomes ▪ As the geneticist, Morgan was interested in the identification of genes ▪ Morgan hypothesized that this gene was located on one of the sex chromosomes, and one of his students, Calvin Bridges, eventually proved this hypothesis to be correct 25 General Features of Chromosomes ▪ Chromosomes were discovered in the second half of the nineteenth century by a German cytologist, W. Waldeyer ▪ Subsequent investigations with many different organisms established that chromosomes are structures within living cells that contain the genetic material ▪ Genes are physically located within chromosomes ▪ Biochemically, each chromosome contains a very long segment of DNA, which is the genetic material, and proteins, which are bound to the DNA and provide it with an organized structure ▪ In eukaryotic cells, this complex between DNA and proteins is called chromatin 26 Eukaryotic Chromosomes Are Examined Cytologically to Yield a Karyotype ▪ Cytogenetics is the field of genetics that involves the microscopic examination of chromosomes ▪ The most basic observation that a cytogeneticist can make is to examine the chromosomal composition of a particular cell ▪ They are best seen by applying dyes to dividing cells; during division, the material in a chromosome is packed into a small volume, giving it the appearance of a tightly organized cylinder ▪ The consequence of this packing is that distinctive shapes and numbers of chromosomes become visible with a light microscope 27 Preparing cells for a karyotype 28 The slide is viewed by a light microscope 29 For a diploid human cell, two complete sets of chromosomes from a single cell constitute a karyotype of that cell 30 Within a species, the number of chromosomes is almost always an even multiple of a basic number ▪ In humans, for example, the basic number is 23; mature eggs and sperm have this number of chromosomes ▪ Most other types of human cells have twice as many (46), although a few kinds, such as some liver cells, have four times (92) the basic number ▪ The haploid, or basic, chromosome number (n) defines a set of chromosomes called the haploid genome ▪ Most somatic cells contain two of each of the chromosomes in this set and are therefore diploid (2n) ▪ Cells with four of each chromosome are tetraploid (4n), those with eight of each are octoploid (8n). 31 32  Sex Chromosomes ▪ In 1901, Clarence McClung, who studied grasshoppers, was the first to suggest that male and female sexes are due to the inheritance of particular chromosomes ▪ In grasshoppers, females have one more chromosome than males. This extra chromosome is called the X chromosome ▪ Females of these species have two X chromosomes, and males have only one; thus, females are cytologically XX and males are XO, where the “O” denotes the absence of a chromosome 22+ 22+ XO XX 33 ▪ During meiosis in the female, the two X chromosomes pair and then separate, producing eggs that contain a single X chromosome ▪ During meiosis in the male, the solitary X chromosome moves independently of all the other chromosomes and is incorporated into half the sperm; the other half receive no X chromosome ▪ Thus, when sperm and eggs unite, two kinds of zygotes are produced: XX, which develop into females, and XO, which develop into males ▪ Because each of these types is equally likely, the reproductive mechanism preserves a 1:1 ratio of males to females in these species 34 ▪ In many other animals, including humans, males and females have the same number of chromosomes ▪ This numerical equality is due to the presence of a chromosome in the male, called the Y chromosome, which pairs with the X during meiosis ▪ The Y chromosome is morphologically distinguishable from the X chromosome ▪ In humans, for example, the Y is much shorter than the X, and its centromere is located closer to one of the ends ▪ The material common to the human X and Y chromosomes is limited, consisting mainly of short segments near the ends of the chromosomes 35 ▪ During meiosis in the male, the X and Y chromosomes separate from each other, producing two kinds of sperm, X-bearing and Y-bearing; the frequencies of the two types are approximately equal ▪ XX females produce only one kind of egg, which is X-bearing ▪ If fertilization were to occur randomly, approximately half the zygotes would be XX and the other half would be XY, leading to a 1:1 sex ratio at conception The X and Y chromosomes are called sex chromosomes All the other chromosomes in the genome are called autosomes 36 The Chromosome Theory of Heredity ▪ By 1910 many biologists suspected that genes were situated on chromosomes, but they did not have definitive proof. ▪ Researchers needed to find a gene that could be unambiguously linked to a chromosome. ✓The gene be defined by a mutant allele and that the chromosome be morphologically distinguishable ✓The pattern of gene transmission had to reflect the chromosome’s behavior during reproduction American biologist Thomas H. Morgan discovered a particular eye color mutation in the fruit fly, Drosophila melanogaster 37 Why Drosophila melanogaster ? ✓It was ideally suited for genetics research because it reproduced quickly and prolifically and was inexpensive to rear in the laboratory ✓In addition, it had only four pairs of chromosomes, one being a pair of sex chromosomes—XX in the female and XY in the male ✓The X and Y chromosomes were morphologically distinguishable from each other and from each of the autosomes ▪ Through careful experiments, Morgan was able to show that the eye color mutation was inherited along with the X chromosome, suggesting that a gene for eye color was physically situated on that chromosome 38 Morgan’s experiment studying the inheritance of white eyes in Drosophila ▪ Morgan’s experiments commenced with his discovery of a mutant male fly that had white eyes instead of the red eyes of wild-type flies 39 ▪ When this male was crossed to wild-type females, all the progeny had red eyes, indicating that white was recessive to red. ▪ When these progeny were intercrossed with each other, Morgan observed a peculiar segregation pattern: all of the daughters, but only half of the sons, had red eyes; the other half of the sons had white eyes. ▪ This pattern suggested that the inheritance of eye color was linked to the sex chromosomes. A gene for eye color was present on the X chromosome, but not on the Y, and that the white and red phenotypes were due to two different alleles (mutant allele w; wild type allele 𝒘+ ) 40 Morgan Carried Out Additional Experiments To Confirm The Elements Of His Hypothesis ▪ In one he crossed F1 females assumed to be heterozygous for the eye color gene to mutant white males. ▪ As he expected, half the progeny of each sex had white eyes, and the other half had red eyes. 41 ▪ In another experiment, he crossed white-eyed females to red-eyed males. ▪ This time, all the daughters had red eyes, and all the sons had white eyes. ▪ When he intercrossed these progeny, Morgan observed the expected segregation: half the progeny of each sex had white eyes, and the other half had red eyes 42 Nondisjunction As Proof of The Chromosome Theory ▪ Morgan showed that a gene for eye color was on the X chromosome of Drosophila by correlating the inheritance of that gene with the transmission of the X chromosome during reproduction. ▪ However, it was one of his students, C. B. Bridges, who secured proof of the chromosome theory by showing that exceptions to the rules of inheritance could also be explained by chromosome behavior. 43 44 ▪ Bridges’ ability to explain the exceptional progeny that came from these crosses showed the power of the chromosome theory. ▪ Each of the exceptions was due to anomalous chromosome behavior during meiosis. ▪ Bridges called the anomaly nondisjunction because it involved a failure of the chromosomes to disjoin during one of the meiotic divisions. ▪ This failure could result from faulty chromosome movement, imprecise or incomplete pairing, or centromere malfunction. ❑ These early studies with Drosophila—primarily the work of Morgan and his students—greatly strengthened the view that all genes were located on chromosomes and that Mendel’s principles could be explained by the transmissional properties of chromosomes during reproduction. This idea, called the Chromosome Theory of heredity, stands as one of the most important achievements in biology. 45 46  Duchenne Muscular Dystrophy (DMD) Mechanism : This disorder is caused by mutations in the dystrophin gene, which is essential for maintaining muscle cell integrity. The mutations lead to a lack of functional dystrophin, causing progressive muscle weakness and degeneration. Males are predominantly affected, and females are usually carriers who may show milder symptoms. Hemophilia A Mechanism : Hemophilia A results from mutations in the factor VIII gene, which is crucial for blood clotting. The absence or reduced activity of factor VIII leads to prolonged bleeding and poor clot formation. Since the gene is located on the X chromosome, males are typically affected, while females may be carriers. Fragile X Syndrome Mechanism : Caused by an expansion of the CGG trinucleotide repeat affecting the FMR1 gene on the X chromosome. In individuals with Fragile X, the expanded repeats lead to hypermethylation of the gene's promoter, silencing gene expression and resulting in a deficiency of the FMRP protein, which is vital for neural development. This condition leads to intellectual disability, behavioral challenges, and characteristic physical features. 47 The Chromosomal Basis of Mendel’s Principles ▪ Mendel established two principles of genetic transmission: 1. The alleles of a single gene segregate from each other 2. The alleles of two different genes assort independently ▪ The finding that genes are located on chromosomes made it possible to explain these principles (as well as exceptions to them) in terms of the meiotic behavior of chromosomes. 48  Mendel’s Principle of Segregation is therefore based on the The Principle of Segregation separation of homologous chromosomes during the anaphase of the first meiotic division 49 The Principle of Independent Assortment 50 51 ▪ Because there are two pairs of chromosomes, there are two distinguishable metaphase alignments: 𝑨𝑩 𝑨𝒃 OR 𝒂𝒃 𝒂𝑩 ▪ Each of these alignments is equally likely. ▪ Here the space separates different pairs of chromosomes, and the bar separates the homologous members of each pair. ▪ During anaphase, the alleles above the bars will move to one pole, and the alleles below them will move to the other. ▪ When disjunction occurs, there is therefore a 50 percent chance that the A and B alleles will move together to the same pole and a 50 percent chance that they will move to opposite poles. ▪ Similarly, there is a 50 percent chance that the a and b alleles will move to the same pole and a 50 percent chance that they will move to opposite poles. 52 ▪ At the end of meiosis, when the chromosome number is finally reduced, half the gametes should contain a parental combination of alleles (A B or a b), and half should contain a new combination (A b or a B). ▪ Altogether, there will be four types of gametes, each one-fourth of the total. ▪ This equality of gamete frequencies is a result of the independent behavior of the two pairs of chromosomes during the first meiotic division. Mendel’s Principle of Independent Assortment is therefore a statement about the random alignment of different pairs of chromosomes at metaphase 53  Autosomal inheritance Autosomal dominant ▪ Autosomal recessive and autosomal dominant genes refer to patterns of inheritance that dictate how certain traits or disorders are passed from parents to offspring through autosomes, which are the chromosomes not involved in determining sex. ▪ These genetic traits are inherited through genes located on the autosomes (chromosomes 1-22). 55 Autosomal dominant ▪ Autosomal dominant inheritance occurs when only one defective gene is necessary to display a trait or disorder. ▪ This means that a single copy of the abnormal gene can cause the disease. In these cases, a parent with an autosomal dominant condition has a 50% chance of passing the gene to their offspring, who will also exhibit the trait or disorder. 56 Autosomal dominant ▪ Example: Huntington’s Disease Huntington’s ▪ This disease is caused by mutations in the HTT gene, which provides instructions for making a protein called huntingtin. ▪ The mutation involves a DNA segment known as a CAG trinucleotide repeat. An excessive number of these repeats leads to the production of an abnormal version of the huntingtin protein, which gradually damages certain brain cells. ▪ This genetic change is dominant, meaning that anyone who inherits the mutated gene will eventually develop the disease. 57 Autosomal dominant 58 Autosomal recessive ▪ Autosomal recessive inheritance requires two copies of an abnormal gene to be present in order for the trait or disorder to develop. ▪ Individuals with only one defective gene (carriers) do not typically show the trait but can pass the gene to their offspring. ▪ When two carriers have a child, there is a 25% chance that the child will inherit both defective copies and express the trait. 59 Autosomal recessive ▪ Example: Cystic Fibrosis ▪ Cystic fibrosis is caused by mutations in the CFTR gene (cystic fibrosis transmembrane conductance regulator), which provides instructions for making a protein that regulates the movement of ions in and out of cells. ▪ The mutations lead to the production of a defective protein, resulting in the buildup of thick mucus in the lungs, pancreas, and other organs. ▪ Individuals must inherit two defective CFTR genes—one from each parent—to have cystic fibrosis. 60 Autosomal recessive 61 Sex-influenced Inheritance ▪ The transmission pattern of X-linked genes depends on the sex of the parents and offspring. Sex can influence traits in other ways as well. ▪ The term sex-influenced inheritance refers to the phenomenon in which an allele is dominant in one sex but recessive in the opposite sex. ▪ Therefore, sex influence is a phenomenon of heterozygotes. ▪ Sex-influenced inheritance should not be confused with sex-linked inheritance. ▪ The genes that govern sex-influenced traits are almost always autosomal, which means they are not located on the X or Y chromosome. 62  In humans, the common form of pattern baldness provides an example of sex-influenced inheritance ▪ The balding pattern is characterized by hair loss on the front and top of the head but not on the sides. ▪ This type of pattern baldness is inherited as an autosomal trait (A common misconception is that this gene is X-linked). ▪ When a male is heterozygous for the baldness allele, he will become bald. ▪ In contrast, a heterozygous female does not become bald. ▪ Women who are homozygous for the baldness Pattern baldness in allele develop the trait, but it is usually John Adams characterized by a significant thinning of the President hair that occurs relatively late in life. (1797-1801) 63 ▪ The sex-influenced nature of pattern baldness is related to the production of the male sex hormone testosterone. ▪ The gene that affects pattern baldness encodes an enzyme called 5-α-reductase, which converts testosterone to 5-α- dihydrotestosterone (DHT) ▪ DHT binds to cellular receptors and affects the expression of many genes, including those in the cells of the scalp. ▪ The allele that causes pattern baldness results in an overexpression of this enzyme. ▪ Because mature males normally make more testosterone than females, this allele has a greater phenotypic effect in males. ▪ However, a rare tumor of the adrenal gland can cause the secretion of abnormally large amounts of testosterone in females. ▪ If this occurs in a woman who is heterozygous Bb, she will become bald. If the tumor is removed surgically, her hair will return to its normal condition. 64 65  X-linked Inheritance Properties of the X and Y Chromosome in Mammals ▪ Sex determination in mammals is determined by the presence of the Y chromosome, which carries the Sry gene. ▪ The X and Y chromosomes also differ in other ways. ▪ The X chromosome is typically much larger than the Y and carries more genes. For example, in humans, researchers estimate that the X chromosome carries about 1200 to 1500 genes, whereas the Y chromosome has 80 to 200 genes. ▪ Genes that are found on only one sex chromosome but not both are called sex-linked genes. ▪ Those on the X chromosome are termed X-linked genes and those on the Y chromosome are termed Y-linked genes, or holandric genes. 67 ▪ Besides sex-linked genes, the X and Y chromosomes also contain short regions of homology where the X and Y chromosomes carry the same genes, which are called pseudoautosomal genes. ▪ In addition to several smaller regions, the human sex chromosomes have three homologous regions. 68 ▪ These regions, which are evolutionarily related, promote the necessary pairing of the X and Y chromosomes that occurs during meiosis I of spermatogenesis. ▪ Relatively few genes are located in these homologous regions. One example is a human gene called Mic2, which encodes a cell surface antigen. ▪ The Mic2 gene is found on both the X and Y chromosomes. It follows a pattern of inheritance called pseudoautosomal inheritance. ▪ The term pseudoautosomal refers to the idea that the inheritance pattern of the Mic2 gene is the same as the inheritance pattern of a gene located on an autosome even though the Mic2 gene is actually located on the sex chromosomes. ▪ As in autosomal inheritance, males have two copies of pseudoautosomally inherited genes, and they can transmit the genes to both daughters and sons. 69 ▪ By comparison, genes that are found only on the X or Y chromosome exhibit transmission patterns that are quite different from genes located on an autosome ▪ A Y-linked inheritance pattern is very distinctive—the gene is transmitted only from fathers to sons. ▪ By comparison, transmission patterns involving X-linked genes are more complex because females inherit two X chromosomes whereas males receive only one X chromosome from their mother. ▪ In humans, recessive X-linked traits are much more easily identified than are recessive autosomal traits. ▪ A male needs only to inherit one recessive allele to show an X- linked trait; however, a female needs to inherit two—one from each of her parents. ▪ Thus, the preponderance of people who show X-linked traits are male. 70 Hemophilia An X-linked Blood-clotting Disorder ▪ People with hemophilia are unable to produce a factor needed for blood clotting; the cuts, bruises, and wounds of hemophiliacs continue to bleed and, if not stopped by transfusion with clotting factor, can cause death. ▪ The principal type of hemophilia in humans is due to a recessive X-linked mutation, and nearly all the individuals who have it are male. These males have inherited the mutation from their heterozygous mothers. ▪ If they reproduce, they transmit the mutation to their daughters, who usually do not develop hemophilia because they inherit a wild-type allele from their mothers. ▪ Affected males never transmit the mutant allele to their sons. 71 X-linked hemophilia in the royal families of Europe. Through intermarriage, the mutant allele for hemophilia was transmitted from the British royal family to the German, Russian, and Spanish royal families. 72  Color Blindness An X-linked Vision Disorder ▪ In humans, color perception is mediated by light-absorbing proteins in the specialized cone cells of the retina in the eye. ▪ Three such proteins have been identified—one to absorb blue light, one to absorb green light, and one to absorb red light ▪ Colorblindness may be caused by an abnormality in any of these receptor proteins. ▪ The classic type of color blindness, involving faulty perception of red and green light, follows an X-linked pattern of inheritance. ▪ About 5 to 10 percent of human males are red-green color blind; however, a much smaller fraction of females, less than 1 percent, has this disability, suggesting that the mutant alleles are recessive 73 ▪ Molecular studies have shown that there are two distinct genes for color perception on the X chromosome; one encodes the receptor for green light, and the other encodes the receptor for red light. ▪ Detailed analyses have demonstrated that these two receptors are structurally very similar, probably because the genes encoding them evolved from an ancestral color-receptor gene. ▪ A third gene for color perception, the one encoding the receptor for blue light, is located on an autosome. 74 Recessive Alleles Often Cause a Reduction in the Amount or Function of the Encoded Proteins ▪ For any given gene, geneticists refer to prevalent alleles in a natural population as wild-type alleles ▪ In large populations, more than one wild-type allele may occur—a phenomenon known as genetic polymorphism ▪ An example of genetic polymorphism: Both yellow and red flowers are common in natural populations of the elderflower orchid, Dactylorhiza sambucina, and both are considered wild type 75 ▪ In addition, random mutations occur in populations and alter preexisting alleles. ▪ Geneticists sometimes refer to these kinds of alleles as mutant alleles to distinguish them from the more common wild-type alleles. ▪ Because random mutations are more likely to disrupt gene function, mutant alleles are often defective in their ability to express a functional protein. ▪ Such mutant alleles tend to be rare in natural populations. ▪ They are typically, but not always, inherited in a recessive fashion. ▪ Among Mendel’s seven traits, the wild-type alleles are tall plants, purple flowers, axial flowers, yellow seeds, round seeds, green pods, and smooth pods. ▪ The mutant alleles are dwarf plants, white flowers, terminal flowers, green seeds, wrinkled seeds, yellow pods, and constricted pods. ▪ We have already noticed that the seven wild-type alleles are dominant over the seven mutant alleles. 76 Why Many Defective Mutant Alleles Are Inherited Recessively? ▪ To understand, we need to take a quantitative look at protein function In a simple dominant/recessive relationship, 50% of the protein encoded by one copy of the dominant allele in the heterozygote is sufficient to produce the wild-type phenotype, in this case, purple flowers. A complete lack of the functional protein results in white flowers. 77 Incomplete Penetrance and Expressivity ▪ Dominant alleles are expected to influence the outcome of a trait when they are present in heterozygotes ▪ Occasionally, however, this may not occur ▪ The phenomenon, called incomplete penetrance, is a situation in which an allele that is expected to cause a particular phenotype does not. ▪ An example of incomplete penetrance in humans is polydactyly— the presence of extra fingers and toes ▪ This condition is due to a dominant mutation, P, that is manifested in some of its carriers. 78  Polydactyly in Humans Phenotype showing extra fingers Antonio Alfonseca - Baseball player with polydactyly 79  Penetrance = % of individuals in a population with a particular genotype, that express the expected phenotype ▪ DD = 100% 10 Fingers and 10 Toes ▪ Dd = 100% >10 Fingers and Toes In reality genotype of 100 people are Dd but only 81 of them had polydactyly 81 % Penetrance OR Incomplete Penetrance 80  Another term used to describe the outcome of traits is the degree to which the trait is expressed, or its expressivity Expressivity = The degree to which a trait is expressed In reality genotype of 100 people are Dd but only 81 of them had polydactyly In the case of polydactyly, the number of extra digits can vary ▪ 20 have 11 Fingers & 10 Toes ▪ 30 have 12 Toes ▪ 31 have 14 Fingers & 14 Toes The range of phenotypes is often due to environmental influences and/or to effects of modifier genes in which one or more genes alter the phenotypic effects of another gene 81  Environmental Effects On Gene Expression In addition to genetics, environmental conditions have a great effect on the phenotype of the individual ▪ For example, the arctic fox (Alopex lagopus) goes through two color phases. ▪ During the cold winter, the arctic fox is primarily white, but in the warmer summer, it is mostly brown. ▪ Such temperature-sensitive alleles affecting fur color are found among many species of mammals. 82  Environmental Effects On Gene Expression Example: Nutrition and Phenylketonuria (PKU): ▪ PKU is a genetic disorder caused by a mutation in the gene responsible for breaking down the amino acid phenylalanine. ▪ The environmental factor in this condition is dietary intake of phenylalanine. ▪ Individuals with PKU, if exposed to a diet high in phenylalanine, can develop severe cognitive disabilities due to the toxic buildup of phenylalanine in the body. ▪ However, if the diet is controlled and phenylalanine intake is restricted from an early age, affected individuals can lead normal lives, showing how dietary environment can modify the expression of a genetic disorder. 83 Environmental Effects On Gene Expression 84  Incomplete Dominance Incomplete dominance occurs when two alleles produce an intermediate phenotype ▪ Although many alleles display a simple dominant/recessive relationship, geneticists have also identified some cases in which a heterozygote exhibits incomplete dominance—a condition in which the phenotype is intermediate between the corresponding homozygous individuals ▪ When the heterozygote’s phenotype is midway between the phenotypes of the two homozygotes, the partially dominant allele is sometimes said to be semidominant ▪ In 1905, the German botanist Carl Correns first observed this phenomenon in the color of the fouro’clock (Mirabilis jalapa) 85 ▪ In Correns’s experiment, a homozygous red-flowered four-o’clock plant was crossed to a homozygous white-flowered plant. ▪ The wild-type allele for red flower color is designated 𝐶 𝑅 and the white allele is 𝐶 𝑊. ▪ As shown here, the offspring had pink flowers. ▪ If these F1 offspring were allowed to self- fertilize, the F2 generation consisted of 1/4 red- flowered plants, 1/2 pink- flowered plants, and 1/4 white-flowered plants. ▪ The F2 generation displayed a 1:2:1 phenotypic ratio, which is different from the 3:1 ratio observed for simple Mendelian inheritance. 86 Incomplete dominance occurs because a heterozygote has an intermediate phenotype ▪ At the molecular level, the allele that causes a white phenotype is expected to result in a lack of a functional protein required for pigmentation ▪ Depending on the effects of gene regulation, the heterozygotes may produce only 50% of the normal protein, but this amount is not sufficient to produce the same phenotype as the 𝐶 𝑅 𝐶 𝑅 homozygote, which may make twice as much of this protein ▪ In this example, a reasonable explanation is that 50% of the functional protein cannot accomplish the same level of pigment synthesis that 100% of the protein can Finally, our opinion of whether a trait is dominant or incompletely dominant may depend on how closely we examine the trait in the individual 87  Incomplete Dominance ▪ Example Curly Hair: ▪ The gene for hair texture has alleles for curly hair and straight hair. ▪ When an individual inherits one allele for curly hair and one allele for straight hair, the result is often wavy hair, which is an intermediate phenotype between the two. hh Hh HH ▪ This demonstrates incomplete dominance as neither the curly nor the straight hair allele is completely dominant, allowing both to influence the hair texture. 88 Overdominance Overdominance occurs when heterozygotes have superior traits ▪ As we have seen, the environment plays a key role in the outcome of traits. ▪ For certain genes, heterozygotes may display characteristics that are more beneficial for their survival in a particular environment. ▪ Such heterozygotes may be more likely to survive and reproduce. ▪ For example, a heterozygote may be larger, disease-resistant, or better able to withstand harsh environmental conditions. ▪ The phenomenon in which a heterozygote has greater reproductive success compared with either of the corresponding homozygotes is called overdominance, or heterozygote advantage. 89 A well-documented example involves a human allele that causes sickle cell disease in homozygous individuals ▪ This disease is an autosomal recessive disorder in which the affected individual produces an altered form of the protein hemoglobin, which carries oxygen within red blood cells. ▪ Most people carry the HbA allele and make hemoglobin A. ▪ Individuals affected with sickle cell disease are homozygous for the HbS allele and produce only hemoglobin S. ▪ This causes their red blood cells to deform into a sickle shape under conditions of low oxygen concentration. ▪ The sickling phenomenon causes the life span of these cells to be greatly shortened to only a few weeks compared with a normal span of 4 months, and therefore, anemia results. ▪ In addition, abnormal sickled cells can become clogged in the capillaries throughout the body, leading to localized areas of oxygen depletion. 90 (a) (b) A comparison of (a) normal red blood cells and (b) those from a person with sickle cell disease 91  Heterozygous have better resistance to malaria ▪ In spite of the harmful consequences to homozygotes, the sickle cell allele has been found at a fairly high frequency among human populations that are exposed to malaria. ▪ The protozoan genus that causes malaria, Plasmodium, spends part of its life cycle within the Anopheles mosquito and another part within the red blood cells of humans who have been bitten by an infected mosquito. ▪ However, red blood cells of heterozygotes, HbAHbS, are likely to rupture when infected by this parasite, thereby preventing the parasite from propagating. ▪ People who are heterozygous have better resistance to malaria than do HbAHbA homozygotes, while not incurring the ill effects of sickle cell disease. 92 The outcome of a cross between two heterozygous individuals 93 Codominance Codominance implies that there is an independence of allele function; Neither allele is dominant, or even partially dominant, over the other ▪ The Mendelian concept that genes exist in no more than two allelic states had to be modified when genes with three, four, or more alleles were discovered. ▪ The ABO group of antigens, which determine blood type in humans, is an example of multiple alleles and illustrates an allelic relationship called codominance. ▪ To understand this concept, we first need to examine the molecular characteristics of human blood types. 94 ▪ The plasma membranes of red blood cells have groups of interconnected sugars—oligo saccharides—that act as surface antigens. ▪ Antigens are molecular structures that are recognized by antibodies produced by the immune system. ▪ On red blood cells, two different types of surface antigens, known as A and B may be found. 95 ▪ The synthesis of these surface antigens is controlled by two alleles, designated 𝑰𝑨 and 𝑰𝑩 , respectively. The i allele is recessive to both 𝑰𝑨 and 𝑰𝑩 ▪ All three alleles are found at appreciable frequencies in human populations; thus, the I gene is said to be polymorphic, from the Greek words for “having many forms.” ▪ The phenomenon in which two alleles are both expressed in the heterozygous individual is called codominance ▪ In this case, the 𝑰𝑨 and 𝑰𝑨 alleles are codominant to each other 96 ▪ As an example of the inheritance of blood type, let’s consider the possible offspring between two parents who are 𝑰𝑨 i and 𝑰𝑩 i ▪ The 𝑰𝑨 i parent makes 𝑰𝑨 and i gametes, and the 𝑰𝑩 i parent makes 𝑰𝑨 and i gametes ▪ These combine to produce 𝑰𝑨 𝑰𝑩 , 𝑰𝑨 i, 𝑰𝑩 i, and ii offspring in a 1:1:1:1 ratio ▪ The resulting blood types are AB, A, B, and O, respectively 97  References ✓ Principles of genetics by D. Peter Snustad, Michael J. Simmons (6th ed.) ✓ Concepts of genetics by Robert J. Brooker (1st ed.) 98  Thank you Best of Luck