CHROMOSOMAL PATTERNS OF INHERITANCE
REGULATION OF GENE ACTIVITY: GENE MUTATION
Chapter 11 Mendelian Patterns of Inheritance
This chapter details Mendel’s discovery of the general laws of heredity including monohybrid and dihybrid crosses, human genetic disorders, and also introduces non-Mendelian genetics.
n
1866 the Austrian monk, Gregor
Mendel, proposed what was to become the foundation of genetics.
Mendel was completely unaware of our modern concept of the gene and that
gene pairs are separated during the cellular event called meiosis.
But nonetheless, while working with garden peas Mendel was able
to deduce that genes (he called them “factors”) occurred in pairs
and that they “assorted” or “segregated” and then recombined
during sexual reproduction. We
now know that assortment or segregation occurs during meiosis
and recombination occurs during fertilization.
Chapter Outline
11.1 Gregor Mendel
A. Gregor Mendel
| Mendel was an Austrian monk. |
| Mendel formulated two fundamental laws of heredity in the early 1860s. |
| He had previously studied science and mathematics at the University of Vienna. |
| At time of his research, he was a substitute science teacher at a local technical high school. |
B. Blending Concept of Inheritance
| This theory stated that offspring would have traits intermediate between those of the parents. |
| Red and white flowers produce pink flowers; any return to red or white offspring was considered instability in genetic material. |
| Charles Darwin wanted to develop a theory of evolution based on hereditary principles; blending theory was of no help. |
1. A blending theory did not account for variation and could not explain species diversity.
2. The particulate theory of inheritance proposed by Mendel can account for presence of differences among members of a population generation after generation.
3. Mendel’s work was unrecognized until 1900; Darwin was never able to use it to support his theory of evolution.
C. Mendel’s Experimental Procedure
| Mendel had a mathematical background and did a statistical study. |
| He prepared his experiments carefully and conducted preliminary studies. |
1. He chose the garden pea, Pisum sativum, because peas were easy to cultivate, had a short generation time, and could be cross-pollinated by hand.
2. From many varieties, Mendel chose 22 true-breeding varieties for his experiments.
3. True-breeding varieties had all offspring like the parents and like each other.
4. Mendel studied simple traits (e.g., seed shape and color, flower color, etc.).
| Mendel traced inheritance of individual traits and kept careful records of numbers. |
| He used his understanding of mathematical principles of probability to interpret results. |
11.2 One-Trait Inheritance
A. Cross-pollination Monohybrid Crosses
| Mendel confirmed that his tall plants always had tall offspring, etc. before crossing two different strains to produce a hybrid by conducting reciprocal crosses. |
| A hybrid is the product of parent organisms that are true-breeding for different forms of one trait. |
| A monohybrid cross is between two parent organisms true-breeding for two distinct forms of one trait. |
| Mendel tracked each trait through two generations. |
1. P generation is the parental generation in a breeding experiment.
2. F1 generation is the first-generation offspring in a breeding experiment.
3. F2 generation is the second-generation offspring in a breeding experiment.
4. He also performed reciprocal crosses of pollen on stigmas (e.g., tall-with-short and short-with-tall).
B. Mendel’s Results
| His results were contrary to those predicted by a blending theory of inheritance. |
| He found that the F1 plants resembled only one of the parents. |
| Characteristic of other parent reappeared in about 1/4 of F2 plants; 3/4 of offspring resembled the F1 plants. |
| Mendel saw that these 3:1 results were possible if: |
1. F1 hybrids contained two factors for each trait, one dominant and one recessive;
2. factors separated when gametes were formed; a gamete carried one copy of each factor;
3. and random fusion of all possible gametes occurred upon fertilization.
| Results of his experiments led Mendel to develop his first law of inheritance: |
1. Mendel’s law of segregation: Each organism contains two factors for each trait; factors segregate in formation of gametes; each gamete contains one factor for each trait; and fertilization gives each new individual two factors for each trait.
2. Mendel’s law of segregation is consistent with a particulate theory of inheritance because many individual factors are passed on from generation to generation.
3. Reshuffling of factors explains variations and why offspring differ from their parents.
C. As Viewed by Modern Genetics
In a
figurative, if not real sense, genes occur in pairs in diploid
organisms. Of course the
only time genes literally “pair up” is during synapsis
of meiosis when the homologous
chromosomes that carry the genes pair up.
A gene pair is
represented by two alleles such as AA (homozygous
dominant), aa (homozygous recessive), and Aa (heterozygous).2
A gene is a portion,
segment, of the DNA molecule found in, or on, a chromosome.
We use the term allele
when we wish to refer a specific form of a gene.
“A” and “a” for example represent different forms
(alleles) of the same gene.
| Each trait in a pea plant is controlled by two alleles, alternate forms of a gene that occur at the same gene locus on homologous chromosomes. |
1. A dominant allele masks or hides expression of a recessive allele; it is represented by an uppercase letter.
2. A recessive allele is an allele that exerts its effect only in the homozygous state; its expression is masked by a dominant allele; it is represented by a lowercase letter.
| Gene locus is specific location of a particular gene on homologous chromosomes. |
| In Mendel’s cross, the parents were true-breeding; each parent had two identical alleles for a trait–they were homozygous, indicating they possess two identical alleles for a trait. |
1. Homozygous dominant genotypes possess two dominant alleles for a trait.
2. Homozygous recessive genotypes possess two recessive alleles for a trait.
| After cross-pollination, all individuals of the F1 generation had one of each type of allele. |
1. Heterozygous genotypes possess one of each allele for a particular trait.
2. The allele not expressed in a heterozygote is a recessive allele.
D. Genotype Versus Phenotype
| Two organisms with different allele combinations can have same outward appearance (e.g., TT and Tt pea plants are both tall; therefore, it is necessary to distinguish between alleles present and the appearance of organism). |
| Genotype refers to the alleles an individual receives at fertilization. |
| Phenotype refers to the physical appearance of the individual. |
E. One-trait Genetics Problems
| First determine which characteristic is dominant; then code the alleles involved. |
| Determine the genotype and gametes for both parents; an individual has two alleles for each trait; each gamete has only one allele for each trait. |
| Each gamete has a 50% chance of receiving either allele. |
F. Laws of Probability
| Probability is the likely outcome a given event will occur from random chance. |
1. With each coin flip there is a 50% chance of heads and 50% chance of tails.
2. Chance of inheriting one of two alleles from a parent is also 50%.
| Multiplicative law of probability states that the chance of two or more independent events occurring together is the product of the probability of the events occurring separately. |
1. Chance of inheriting a specific allele from one parent and a specific allele from another is ˝ x ˝ or 1/4.
2. Possible combinations for the alleles Ee of heterozygous parents are the following:
EE = ˝ x ˝ = 1/4 eE = ˝ x ˝ = 1/4 Ee = ˝ x ˝ = 1/4 ee = ˝ x ˝ = 1/4
| Additive law of probability calculates probability of an event that occurs in two or more independent ways; it is sum of individual probabilities of each way an event can occur; in the above example where unattached earlobes are dominant (EE, Ee, and eE), the chance for unattached earlobes is 1/4 + 1/4 + 1/4 = 3/4. |
G. The Punnett Square
Today
it is convenient to use the Punnett-square method to predict inheritance
based on these simple principles. Restated
differently, the principles behind the Punnett-square are these:
|
Mendel’s law of segregation:
Gene pairs segregate during meiosis such that each haploid
daughter cell gets only one of the two possible alleles.
Gametes carry only one allele from each gene pair.
Gametes from a given parent can only carry one of the alleles
possessed by that parent. If
the parent is homozygous, then the gametes produced are all identical.
Ex. If the parent is “AA,” then the gamete can only be “A.”
Each possible type of gamete produced from a parent is written
along one side of the Punnett-square. |
|
Mendel’s law of independent assortment: the chromosomes of a homologous pair segregate independently of other homologous pairs, thus gene pairs that are not linked to the same homologous chromosomes are also segregated or assorted independently of one another. |
Ex, Parent=AaBb when alleles A& a on one pair of homologous chromosomes and B & b are on another pair of homologous chromosomes, then the possible gamete genotypes are:Four different gametes = AB, ab, Ab, & aB
The
number of gamete genotypes is predicted by
2n where n=#heterozygous pairs
| The Punnett square was introduced by R. C. Punnett and provides a simple method to calculate the probable results of a genetic cross. |
| In a Punnett square, all possible types of sperm alleles are lined up vertically and all possible egg alleles are lined up horizontally; every possible combination is placed in squares. |
| The larger the sample size examined, the more likely the outcome will reflect predicted ratios; a large number of offspring must be counted to observe the expected results; only in that way can all possible genetic types of sperm fertilize all possible types of eggs. |
| We cannot testcross humans in order to count many offspring; therefore in humans, the phenotypic ratio is used to estimate the probability of any child having a particular characteristic. |
| Punnett square uses laws of probability; it does not dictate what the next child will inherit. |
| "Chance has no memory": if two heterozygous parents have first child with attached earlobes (likely in 1/4th of children), a second child born still has 1/4 chance of having attached earlobes. |
H. One-Trait Testcross
| Mendel performed test crosses by crossing his F1 plants with homozygous recessive plants. |
| Results indicated the recessive factor was present in the F1 plants; they were heterozygous. |
| A monohybrid testcross is used between an individual with dominant phenotype and an individual with a recessive phenotype to see if the individual with dominant phenotype is homozygous or heterozygous. |
11.3 Two-Trait Inheritance
A. Two-trait (Dihybrid) Crosses
| This two-trait cross is between two parent organisms that are true-breeding for different forms of two traits; it produces offspring heterozygous for both traits. |
| Mendel observed that the F1 individuals were dominant in both traits. |
B. F1 Plants Self-Pollinate
| Mendel observed four phenotypes among F2 offspring; he deduced second law of heredity. |
| Mendel’s law of independent assortment states members of one pair of factors assort independently of members of another pair; all combinations of factors occur in gametes. |
C. Two-trait Genetics Problems
| Laws of probability indicate a 9:3:3:1 phenotypic ratio of F2 offspring resulting in the following: |
1. 9/16 of the offspring are dominant for both traits;
2. 3/16 of the offspring are dominant for one trait and recessive for the other trait;
3. 3/16 of the offspring are dominant and recessive opposite of the previous proportions; and
4. 1/16 of the offspring are recessive for both traits.
| The Punnett Square for Two-trait Crosses |
1. A larger Punnett square is used to calculate probable results of this cross.
2. A phenotypic ratio of 9:3:3:1 is expected when heterozygotes for two traits are crossed and simple dominance is present for both genes.
3. Independent assortment during meiosis explains these results.
D. Two-Trait Testcross
| A two-trait testcross tests if individuals showing two dominant characteristics are homozygous for both or for one trait only, or is heterozygous for both. |
| If an organism heterozygous for two traits is crossed with another recessive for both traits, the expected phenotypic ratio is 1:1:1:1. |
| In dihybrid genetics problems, the individual has four alleles, two for each trait. |
11.4 Human Genetic Disorders
A. Patterns of Inheritance
| Genetic disorders are medical conditions caused by alleles inherited from parents. |
| An autosome is any chromosome other than a sex (X or Y) chromosome. |
| In a pedigree chart, males are designated by squares, females by circles; shaded circles and squares are affected individuals; line between square and circle represents a union; vertical line leads to offspring. |
| A carrier is a heterozygous individual who has no apparent abnormality but can pass on an allele for a recessively inherited genetic disorder. |
| Autosomal dominant and autosomal recessive alleles have different patterns of inheritance. |
1. Characteristics of autosomal dominant disorders
a) Affected children usually have an affected parent.
b) Heterozygotes are affected. Two affected parents can produce unaffected child; two unaffected parents will not have affected children.
2. Characteristics of autosomal recessive disorders
a) Most affected children have normal parents since heterozygotes have a normal phenotype.
b) Two affected parents always produce an affected child.
c) Close relatives who reproduce together are more likely to have affected children.
B. Autosomal Recessive Disorders
| Tay-Sachs Disease |
1. Usually occurs among Jewish people in the U.S. of central and eastern European descent.
2. Symptoms are not initially apparent; infant’s development begins to slow between four to eight months, neurological and psychomotor difficulties become apparent, child gradually becomes blind and helpless, develops seizures, eventually becomes paralyzed and dies by age of three or four.
3. This results from lack of enzyme hexosaminidase A (Hex A) and the subsequent storage of its substrate, glycosphingolipid, in lysosomes.
4. Primary sites of storage are cells of the brain; accounts for progressive deterioration.
5. There is no treatment or cure.
6. Prenatal diagnosis is possible by amniocentesis or chorionic villi sampling.
| Cystic Fibrosis |
1. This is most common lethal genetic disease in Caucasians in U.S.
2. About 1 in 20 Caucasians is a carrier, and about 1 in 3,000 newborns has this disorder.
3. It increases the production of a viscous form of mucus in the lungs and pancreatic ducts.
a) The resultant accumulation of mucus in the respiratory tract interferes with gas exchange.
b) Digestive enzymes must be mixed with food to supplant the pancreatic juices.
4. New treatments have raised the average life expectancy to up to 35 years.
5. Chloride ions (Cl–) fail to pass plasma membrane proteins.
6. Since water normally follows Cl–, lack of water in the lungs causes thick mucus.
7. The cause is a gene on chromosome 7; attempt to insert gene into nasal epithelium has had little success.
8. Genetic testing for adult carriers and fetuses is possible.
| Phenylketonuria (PKU) |
1. PKU occurs once in every 5,000 births; it is the most common inherited disease of nervous system.
2. It is caused by a lack of an enzyme needed to metabolize amino acid phenylalanine; this results in accumulation of the amino acid in nerve cells of the brain and impairs nervous system development.
3. PKU is caused by a gene on chromosome 12.
4. Now newborns are routinely tested in hospital for high levels of phenylalanine in the blood.
5. If an infant has PKU, the child is placed on diet low in phenylalanine until the brain is fully developed near age seven
B. Autosomal Dominant Disorders
| Neurofibromatosis |
1. This is an autosomal dominant disorder that affects one in 3,500 newborns and is distributed equally around the world.
2. Affected individuals have tan skin spots at birth, which develop into benign tumors.
3. Neurofibromas are lumps under the skin comprised of fibrous coverings of nerves.
4. In most cases, symptoms are mild and patients live a normal life; sometimes symptoms are severe:
a) skeletal deformities, including a large head;
b) eye and ear tumors that can lead to blindness and hearing loss; and
c) learning disabilities and hyperactivity.
d) Such variation is called variable expressivity.
5. The gene that codes for neurofibromatosis was discovered in 1990 to be on chromosome 17.
a) The gene controls production of neurofibromin protein that normally blocks growth signals for cell division.
b) Many types of mutations result in this effect.
c) Some mutations are caused by a gene that moves from another location in the genome.
| Huntington Disease |
1. This leads to progressive degeneration of brain cells, which in turn causes severe muscle spasm, personality disorders, and death in 10–15 years after onset.
2. Most appear normal until they are of middle age and already have had children who might carry the gene; occasionally, first signs of the disease are seen in teenagers or even younger.
3. The gene for Huntington disease is located on chromosome 4.
4. This gene contains many repeats of a base triplet that codes for glutamine in the huntingtin protein; normal persons have 10–15 glutamines; affected persons have 36 or more.
5. A huntingtin protein with over 36 glutamines changes shape and forms large clumps inside neurons; it also attracts other proteins to clump with it .
11.5 Beyond Mendelian Genetics
A. Incomplete Dominance
| Incomplete dominance: offspring show traits intermediate between two parental phenotypes. |
1. True-breeding red and white-flowered four-o’clocks produce pink-flowered offspring.
2. Incomplete dominance has a biochemical basis; the level of gene-directed protein production may be between that of the two homozygotes.
3. One allele of a heterozygous pair only partially dominates expression of its partner.
4. This does not support a blending theory; parental phenotypes reappear in F2 generation.
B. Human Examples of Incomplete Dominance
| Curly versus Straight Hair |
1. A curly-haired Caucasian and a straight-haired Caucasian will have wavy-haired offspring.
2. Two wavy-haired parents will produce a 1:2:1 ratio of curly-wavy-straight hair children.
| Sickle-cell disease is a blood disorder controlled by incompletely dominant alleles. |
1. Codominance occurs when alleles are equally expressed in a heterozygote.
2. HbAHbA individuals are normal; HbSHbS have sickle-cell disease; HbAHbS have sickle-cell trait.
3. With sickle-cell disease, red blood cells are irregular in shape (sickle-shaped) rather than biconcave, due to abnormal hemoglobin that the cells contain.
4. Due to irregular shape, sickle-shaped red blood cells clog vessels and break down; results in poor circulation, anemia, low resistance to infection, hemorrhaging, damage to organs, jaundice, and pain of abdomen and joints; when a gene affects many traits, this is called pleiotropy.
5. Persons heterozygous for sickle-cell (HbAHbS) usually lack sickle-cell symptoms unless deprived of water or oxygen.
6. In malaria regions of Africa, infants heterozygous (HbAHbS) for sickle-cell allele have better chance of surviving; malaria parasite dies as potassium leaks from sickled cells.
7. Possible cures focus on bone marrow transplants and drugs that turn on genes for fetal hemoglobin in adults.
C. Multiple Allelic Traits
| This occurs when a gene has many allelic forms or alternative expressions. |
| ABO Blood Types |
1. The ABO system of human blood types is a multiple allele system.
2. Two dominant alleles (IA and IB) code for presence of A and B glycoproteins on red blood cells.
3. This also includes a recessive allele (iO) coding for no A or B glycoproteins on red blood cells.
4. As a result, there are four possible phenotypes (blood types): A, B, AB, and O
5. This is a case of codominance, where both alleles are fully expressed.
| The Rh factor is inherited independently from the ABO system; the Rh+ allele is dominant. |
D. Polygenic Inheritance
Comparison of traits between individuals for traits governed by a single gene pair reveals discontinuous variation, ex. tongue rolling, either you can or you can’t, only 2 phenotypes, no intermediates. But most traits exhibit continuous variation- a range of phenotypes for a given trait, that is there are many possible phenotypes, not just two or three. Continuous variation is a result of polygenic inheritance - when two or more gene pairs control a single trait (see graphs on p. 190 & p. 210 depicting the variation in traits under polygenic control).
Skin color is another example of a trait under polygenic inheritance. Darkness of skin color is determined by the production of the pigment melanin. Consider this simplified example: Two genes, A & B, contribute to melanin production. Only the alleles represented by capital letters contribute to melanin production. Each person has four alleles (two gene pairs) so the following are possible.
Genotype
Phenotype
AABB
Very dark
AaBB or AABb
Dark
AaBb or aaBB or Aabb
Medium
Aabb or aaBb
light
aabb
very light
Continuous
variation is exhibited in the variation range along the
"continuum" from "very dark" to "very
light"
| Polygenic inheritance occurs when one trait is governed by two or more sets of alleles. |
| Dominant alleles have a quantitative effect on the phenotype: each adds to the effect. |
| The more genes involved, the more continuous is the variation in phenotypes, resulting in a bell-shaped curve. |
| Crosses of white and dark-red wheat seeds produce seeds with seven degrees of intermediate colors due to genes at three separate loci. |
| Human Examples of Polygenic Inheritance |
1. A hybrid cross for skin color provides a range of intermediates.
2. Parents with intermediate skin color can produce children with the full range of skin colors.
3. Albinism, where one gene interferes with the expression of others, is an example of epistasis.
E. Polygenic Disorders
| This includes cleft lip, clubfoot, congenital dislocations of the hip, hypertension, diabetes, schizophrenia, allergies and cancers. |
| Behavioral traits including suicide, phobias, alcoholism, and homosexuality may be associated with particular genes but are not likely completely predetermined. |
| Environment and the Phenotype |
1. In water buttercups, the aquatic environment dramatically influences the structure of the plant.
2. Temperature triggers primrose to develop white flowers when grown above 32oC and red flowers when grown at 24oC.
3. The coats of Siamese cats and Himalayan rabbits have darker tipped ears, nose, paws, etc. due to the enzyme encoded by an allele is only active at low temperatures at the extremities.
The chromosomal theory of inheritance, sex chromosomes, gene linkage, and chromosomal mutations are detailed in this chapter. The human aspects of chromosomal abnormalities are presented.
Chapter Outline
12.1 Chromosomal Inheritance
A. Chromosomal Theory of Inheritance
Genes are located on chromosomes; behavior of chromosomes and genes is therefore similar during sexual reproduction. Chromosomes can be categorized as two types: 1. Autosomes are non-sex chromosomes that are the same number and kind between sexes.
2. Sex chromosomes determine if the individual is male or female.
Sex chromosomes in the human female are XX; those of the male are XY. Males produce X-containing and Y-containing gametes; therefore males determine the sex of offspring. Besides genes that determine sex, sex chromosomes carry many genes for traits unrelated to sex. X-linked gene is any gene located on X chromosome; used to describe genes on X chromosome that are missing on the Y chromosome. B. X-Linked Alleles
Work with fruit flies by Thomas Hunt Morgan (Columbia University) confirmed genes were on chromosomes. 1. Fruit flies are easily and inexpensively raised in common laboratory glassware.
2. Females only mate once and lay hundreds of eggs.
3. The fruit fly generation time is short, allowing rapid experiments.
Fruit flies have an XY system similar to the human system; therefore experiments are similar to the human situation. 1. Newly discovered mutant male fruit fly had white eyes.
2. Cross of the hybrids from the white-eyed male crossed with a dominant red-eyed female yielded the expected 3:1 red-to-white ratio; however, all of the white-eyed flies were males!
3. An allele for eye color on the X but not on the Y chromosome supports the results of this cross.
4. Behavior of this allele corresponds to the behavior of the chromosome; this confirmed the chromosomal theory of inheritance.
X-Linked Problems 1. X-linked alleles are designated as superscripts to the X chromosome.
2. Heterozygous females are carriers; they do not show the trait but can pass it on.
3. Males are never carriers but express the one allele on the X chromosome, whether it is dominant or recessive.
4. One form of color-blindness is X-linked recessive.
C. Human X-Linked Disorders
More males have X-linked traits because recessive alleles on the X chromosome in males are expressed in males. Color Blindness 1. Color blindness can be an X-linked recessive disorder involving mutations of genes coding for green or red sensitive cone cells, resulting in an inability to perceive green or red, respectively; the pigment for blue-sensitive protein is autosomal.
2. About 8% of Caucasian men have red-green color blindness.
Muscular Dystrophy 1. Duchenne muscular dystrophy is the most common form and is characterized by wasting away of muscles, eventually leading to death; it affects one out of every 3,600 male births.
2. This X-linked recessive disease involves a mutant gene that fails to produce protein dystrophin.
3. Symptoms (e.g., waddling gait, toe walking, frequent falls, difficulty in rising) soon appear.
4. Muscle weakens until the individual is confined to wheelchair; death usually occurs by age 20.
5. Affected males are rarely fathers; the gene passes from carrier mother to carrier daughter.
6. Lack of dystrophin protein causes calcium ions to leak into muscle cells; this promotes action of an enzyme that dissolves muscle fibers.
7. As body attempts to repair tissue, fibrous tissue forms and cuts off blood supply.
8. A test now detects carriers of Duchenne muscular dystrophy; treatments are under research.
Hemophilia 1. About one in 10,000 males is a hemophiliac with impaired ability of blood to clot.
2. Hemophilia has two types: Hemophilia A is due to absence of clotting factor IX; Hemophilia B is due to absence of clotting factor VIII.
3. Hemophiliacs bleed externally after an injury and also suffer internal bleeding around joints.
4. Hemorrhages stop with transfusions of blood (or plasma) or concentrates of clotting protein.
5. Factor VIII is now available as a genetic engineering product.
6. Of Queen Victoria’s 26 offspring, five grandsons had hemophilia and four granddaughters were carriers.
Fragile X Syndrome 1. In this case, the X chromosome is nearly broken; most often found in males.
2. This affects one in 1,500 males and one in 2,500 females.
3. As children, they are often hyperactive or autistic with delayed or repetitive speech.
4. As adults, males usually have larger testes, unusually protruding ears, and other symptoms.
5. However, about one-fifth of males with fragile X do not show symptoms.
6. Fragile X passes from a symptomless male carrier to grandson.
7. It has been traced to excessive repeats of base triplet CGG (cytosine, guanine, guanine); up to 230 copies compared to normal 6–to–50 copies.
12.2 Gene Linkage
A. Linkage Groups
| Fruit flies have four pairs of chromosomes to hold thousands of genes; therefore each chromosome must hold many genes. |
| All alleles on a chromosome form a linkage group that stays together except when crossing over. |
| Crossing-over causes recombinant gametes and at fertilization, recombinant phenotypes. |
| Linked alleles do not obey Mendel’s laws because they tend to go into the gametes together. |
B. Chromosome Mapping
| The percentage of recombinant phenotypes measures distance between genes to map the chromosomes. |
| Crosses involving linked genes do not give same results as unlinked genes. |
| A heterozygote forms only two types of gametes and produces offspring with only two phenotypes. |
C. Linkage Data
| Linked genes indicate the distance between genes on the chromosomes. |
| If 1% of crossing-over equals one map unit, then 6% recombinants reveal 6 map units between genes. |
| If crosses are performed for three alleles on a chromosome, only one map order explains map units. |
| Humans have few offspring and a long generation time, and it is not ethical to designate matings; therefore biochemical methods are used to map human chromosomes. |
12.3 Changes in Chromosome Numbers
A. Mutations
| Changes in chromosomes or genes that pass to offspring if they occur in gametes. |
| Mutations increase the amount of variation among offspring. |
| Chromosomal mutations include changes in chromosome number and structure. |
B. Polyploidy
| Eukaryotes with more than the 2n number of chromosomes are polyploids. |
| Terms indicate how many sets of chromosomes are present: (triploids [3n], tetraploids [4n], etc.). |
| Polyploidy does not increase variation in animals; judging from trisomies, it would be lethal. |
| Polyploidy is a major evolutionary mechanism in plants; it is probably involved in 47% of flowering plants including major crops. |
| Hybridization in plants can result in doubled number of chromosomes; an even number of chromosomes can undergo synapsis during meiosis; successful polyploidy results in a new species. |
C. Monosomy and Trisomy
| Monosomy (2n – 1) occurs when an individual has only one of a particular type of chromosome. |
| Trisomy (2n + 1)occurs when an individual has three of a particular type of chromosome. |
| Nondisjunction is the failure of chromosomes to separate; it is more common during meiosis. |
| Monosomy and trisomy occur in plants and animals; in autosomes of animals, it is generally lethal. |
| Down syndrome is most common autosomal trisomy, involves chromosome 21. |
1. Most often, Down syndrome results in three copies of chromosome 21 due to nondisjunction during gametogenesis.
2. In 23% of cases, the sperm had the extra chromosome 21.
3. In 5% of cases, there is translocation with chromosome 21 attached to chromosome 14; this translocation could have occurred generations earlier and is not age-related.
4. Chances of a woman having a Down syndrome child increase with age, starting at age 40.
5. Chorionic villi sampling testing or amniocentesis and karyotyping detects a Down syndrome child; however, risks for young women exceed likelihood of detection.
6. A Down syndrome child has tendency for leukemia, cataracts, faster aging, and mental retardation.
7. Gart gene, located on bottom third of chromosome 21, leads to high level of purines and is associated with mental retardation; future research may lead to suppression of this gene.
D. Changes in Sex Chromosome Number
| Nondisjunction during oogenesis can result in too few or too many X chromosomes; nondisjunction during spermatogenesis can result in missing or too many Y chromosomes |
| Turner syndrome females have only one sex chromosome, an X. |
1. Turner females are short, have a broad chest and folds of skin on back of neck.
2. Ovaries of Turner females never become functional; therefore, females do not undergo puberty.
3. They usually have normal intelligence and can lead fairly normal lives with hormone supplements.
| Klinefelter syndrome males have one Y chromosome and two or more X chromosomes. |
1. Affected individuals are sterile males; the testes and prostate are underdeveloped.
2. Individuals have large hands and feet, long arms and legs, and lack facial hair.
3. Presence of the Y chromosome drives male formation but more than two X chromosomes may result in mental retardation.
4. Barr body, usually only seen in female cell nuclei, is seen in this syndrome due to the two X chromosomes.
| Poly-X females have three or more X chromosomes and extra Barr bodies in the nucleus. |
1. There is no increased femininity; most lack any physical abnormalities.
2. XXX individuals are not mentally retarded but may have delayed motor and language development; XXXX females are usually tall and severely mentally retarded.
3. Many experience menstrual irregularities but many menstruate regularly and are fertile.
| Jacobs syndrome (XXY) are males with two Y chromosomes instead of one. |
1. This only results from nondisjunction during spermatogenesis.
2. Males are usually taller than average, suffer from persistent acne, and tend to have speech and reading problems.
3. Earlier claims that XYY individuals were likely to be aggressive were not correct.
12.4 Changes in Chromosome Structure
A. Changes in Chromosomal Structure
| Environmental factors including radiation, chemicals, and viruses, can cause chromosomes to break; if the broken ends do not rejoin in the same pattern, this causes a change in chromosomal structure. |
B. Examples of Changes in Chromosomal Structure
| Deletion: a type of mutation in which an end of a chromosome breaks off or when two simultaneous breaks lead to the loss of a segment. |
| Translocation: a chromosomal segment is removed from one chromosome and inserted into another, nonhomologous chromosome; In Down syndrome, 5% of cases are due to a translocation between chromosome 21 and 14, a factor that runs in the family of the father or mother. |
| Duplication is the presence of a chromosomal segment more than once on the same chromosome. |
1. A broken segment from one chromosome can simply attach to its homologue or unequal crossing-over may occur.
2. Duplication may also involve an inversion where a segment that has become separated from the chromosome is reinserted at the same place but in reverse; the position and sequence of genes are altered.
C. Human Syndromes
| Deletion Syndromes |
1. Williams syndrome occurs when chromosome 7 loses an end piece: children look like pixies, have poor academic skills but good verbal and musical skills; lack of elastin causes cardiovascular problems and skin aging.
Cri du chat syndrome is deletion in which an individual has a small head, is mentally retarded, has facial abnormalities, and abnormal glottis and larynx resulting in a cry resembling that of a cat.
| Translocation Syndromes |
1. If a translocation results in the normal amount of genetic material, the person will remain healthy; if a person inherits only one of the translocated chromosomes, that person may have only one allele or three alleles rather than the normal two.
2. In Alagille syndrome, chromosomes 2 and 20 exchange segments, causing a small deletion on chromosome 20 that may produce some abnormalities.
Considerable history of early research leading to discovery of DNA as the genetic material is described before detailing the structure of DNA and its method of replication.
Chapter Outline
13.1 The Genetic Material
A. Early researchers knew that the genetic material must be:
| able to store information used to control both the development and the metabolic activities of cells; |
| stable so it can be replicated accurately during cell division and be transmitted for generations; and |
| able to undergo mutations providing genetic variability required for evolution. |
B. Previous Knowledge About DNA
| Knowing the chemistry of DNA was essential to discovery that DNA is genetic material. |
| In 1869, Swiss chemist Friedrich Miescher removed nuclei from pus cells and isolated DNA "nuclein"; it was rich in phosphorus and lacked sulfur. |
| Nuclein was analyzed by other scientists who found that it contained an acid: nucleic acid. |
| Two types of nucleic acids were soon discovered: DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). |
| In the early twentieth century, discovery that nucleic acids contain four types of nucleotides. |
1. DNA was composed of repeating units, each of which always had just one of each of four different nucleotides (A, T, G, or C).
2. In this model, DNA could not vary between species and therefore could not be the genetic material; therefore some other protein component was expected to be the genetic material.
C. Transformation of Bacteria
| In 1931, bacteriologist Frederick Griffith experimented with Streptococcus pneumoniae (a pneumococcus) that causes pneumonia in mammals. |
| Griffith injected mice with two strains of pneumococcus: an encapsulated (S) strain and a non-encapsulated (R) strain. |
1. The S strain is virulent (the mice died); it has a mucous capsule and forms shiny colonies.
2. The R strain is not virulent (the mice lived); it has no capsule and forms dull colonies.
| In an effort to determine if the capsule alone was responsible for the virulence of the S strain, he injected mice with heat-killed S strain bacteria; the mice lived. |
| Finally, he injected mice with a mixture of heat-killed S strain and live R strain bacteria. |
1. The mice died and living S strain pneumococcus were recovered from their bodies.
2. Griffith concluded some substance necessary to synthesis of the capsule and, therefore, virulence must pass from dead S strain bacteria to living R strain bacteria so the R strain were transformed.
3. This change in phenotype of the R strain bacteria must be due to a change in their genotype, which suggested that the transforming substance may have passed from S strain to R strain.
D. DNA: The Transforming Substance
| Oswald Avery and his coworkers reported that the transforming substance was DNA. |
| Purified DNA is capable of bringing about the transformation; their evidence included the following: |
1. DNA from S strain pneumococcus causes R strain bacteria to be transformed.
2. Enzymes that degrade proteins cannot prevent transformation, nor do enzymes that digest RNA.
3. Digestion of the transforming substance with enzyme that digests DNA prevents transformation.
4. Molecular weight of the transforming substance is great enough for some genetic variability
| Their experimental results demonstrated DNA is genetic material and DNA controls biosynthetic properties of a cell. |
E. Transformation Experiments Today
| Transformation experiments today are common in high schools and research labs. |
| Transformation occurs whenever organisms receive foreign DNA and receive a new trait. |
| Modern experiments with bacteria show some can take up DNA to gain penicillin resistance. |
F. Reproduction of Viruses
| Bacteriophage is a virus that infects bacteria; it consists only of a protein coat surrounding a nucleic acid core. |
| Bacteriophage T2 is a virus that infects the bacterium Escherichia coli (E. coli), a species of intensely studied bacteria that normally lives within the human gut. |
| In 1952, Alfred Hershey and Martha Chase used bacteriophage T2 in their experiments. |
1. The purpose of their experiments was to see which of the bacteriophage components—the protein coat or the DNA—entered bacterial cells and directed reproduction of the virus.
2. In two separate experiments, they labeled the protein coat with 35S and the DNA with 32P.
3. Viral coats are sheared away from bacterial cells; they are separated by centrifugation.
4. Results: radioactive 32P alone is taken up by bacterial host and incorporated in virus reproduction.
5. This result reinforced the notion that DNA (and not the protein) is the genetic material.
13.2 The Structure of DNA
A. Nucleotide Data
DNA Structure – discovered in 1953 by James Watson (U.S.) & Francis Crick (Britain)
Deoxyribonucleic Acid is a double stranded molecule, each strand consisting of repeating subunits called nucleotides - monomers of DNA that contain nitrogenous bases [4 kinds in DNA]:
Adenine
(A), Thymine (T), Cytosine (C), and Guanine (G).
A . . . T
T . . . A
C . . . G
G . . . C
The
sequence of N-bases of 2nd strand is dictated by
the 1st strand, such that Adenine pairs with Thymine
and Cytosine pairs with Guanine (this is complementary
base pairing). To complete this model of DNA
structure, imagine a flexible
ladder where the rungs of the latter are
DNA
structure – DNA is a double stranded polymer of
(named
for their nitrogenous bases Adenine, Thymine, Cytosine,
(Complementary base pairing explains a lot about molecular genetics.)
II.
DNA Function – the following are functional aspects of DNA
1. DNA Replication – DNA molecules are copied or cloned
2. DNA stores genetic information in the form of a molecular code
3. DNA releases specific genetic instructions at appropriate times via protein synthesis
4.
DNA is capable of mutating (the ultimate source of all allelic
variation!)
| In the 1940s, Erwin Chargaff analyzed the base content of DNA using new chemical techniques. |
| It was known DNA contained four different nucleotides: |
1. two with purine bases, adenine (A) and guanine (G); a purine is a type of nitrogen-containing base having a double-ring structure.
2. two with pyrimidine bases, thymine (T) and cytosine (C); a pyrimidine is a type of nitrogen-containing base having a single-ring structure.
| The results of his analysis proved DNA does have the variability necessary to code genetic material. |
| Chargaff discovered that for a species, DNA has the constancy required of genetic material. |
| This constancy is given in Chargaff’s rules: |
1. The amount of A, T, G, and C in DNA varies from species to species.
2. In each species, the amount of A = T and the amount of G = C.
| The tetranucleotide hypothesis (proposing DNA was repeating units of one of four bases) was disproved; each species had its own constant base composition. |
B. Variation in Base Sequence
| The variability is staggering; a human chromosome contains about 140 million base pairs. |
| Since any of the four possible nucleotides can be present at each nucleotide position, the total number of possible nucleotide sequences is 4140 x 106 = 4140,000,000. |
C. Diffraction Data
| Rosalind Franklin, a student at King’s College, produced X-ray diffraction photographs. |
| Franklin’s work provided evidence that DNA had the following features: |
1. DNA is a helix.
2. One part of the helix is repeated.
C. The Watson and Crick Model
| American James Watson joined with Francis H. C. Crick in England to work on structure of DNA. |
| Watson and Crick received the Nobel Prize in 1962 for their model of DNA. |
| Using information generated by Chargaff and Franklin, Watson and Crick built a model of DNA as a double helix; sugar-phosphate molecules were on the outside, paired bases were on the inside. |
| Their model was consistent with both Chargaff’s rules and the dimensions of the DNA polymer provided by Franklin’s photograph of X-ray diffraction of DNA. |
| Complementary base pairing is the paired relationship between purines and pyrimidines in DNA, such that A is hydrogen-bonded to T and G is hydrogen-bonded to C. |
DNA Anatomy: http://www.johnkyrk.com/DNAanatomy.html
13.3 Replication of DNA
A. DNA replication is the process of copying a DNA molecule.
| Unwinding: old strands of the parent DNA molecule are unwound as weak hydrogen bonds between the paired bases are unzipped and broken by the enzyme helicase. |
| Complementary base pairing: free nucleotides present in the nucleus bind with complementary bases on unzipped portions of the two strands of DNA; this process is catalyzed by DNA polymerase. |
| Joining: complimentary nucleotides bond to each other to form new strands; each daughter DNA molecule contains an old strand and a new strand; this process is also catalyzed by DNA polymerase. |
| DNA replication must occur before a cell can divide; in cancer, drugs with molecules similar to the four nucleotides are used to stop replication. |
B. Replication is Semiconservative
DNA Replication-produces 2 exact copies of DNA (see fig. 14.7 in Mader)
Requires 2 enzymes: DNA Helicase and DNA Polymerase (these enzymes are also important in genetic engineering)
