Ch. 15- Genetics

Examples of genetic disorders-

-** PHENYLKOTONURIA NEEDS TO BE PUT IN HERE.***** PLease -Sickle-cell anemia is a disease in which red blood cells become crescent-shaped because they contain defective hemoglobin. The sickle-cell hemoglobin carries less oxygen. This disease is caused by a substitution of valine (coded by GUA or GUG) for glutamic acid (coded by GAA or GAG) because of a single base-pair substitution in the gene coding for hemoglobin. While the decreased ability to carry oxygen can have negative effects on patients, these individuals do have less severe symptoms of malaria should they become infected, indicating a possible evolutionary advantage in regions where malaria infection is common.

Transduction

A bacteriophage is a virus that infects its host bacterium by attaching to the bacterium, boring a hole through the bacterial cell wall, and injecting its viral DNA while its protein coat remains attached to the cell wall. Transduction occurs when fragments of the bacterial chromosome become packaged into the viral progeny produced during such a viral infection. These virions may infect other bacteria and introduce new genetic arrangements through recombination with the new host cell's DNA. The closer two genes are to one another on a chromosome, the more likely they will be to transduce together; this fact allows geneticists to map genes to a high degree of precision.

GENETIC PROBLEMS

Although genetic replication is very accurate, chromosome number and structure can be altered by abnormal cell division during meiosis or by mutagenic agents. This can result in the appearance of abnormal characteristics of the offspring in question.

Genetic Variance

Bacterial cells reproduce by binary fission and proliferate very rapidly under favorable conditions. Although binary fission is an asexual process, bacteria have three mechanisms for increasing the genetic variation of a population: transformation, conjugation, and transduction.

Chromosomal breakage

Chromosomal breakage may occur spontaneously or be induced by environmental factors, such as mutagenic agents and X-rays. The chromosome that loses a fragment is said to have a deficiency.

Codominance

Co-dominance occurs when multiple alleles exist for a given gene and more than one of them is dominant. Each dominant allele is fully dominant when combined with a recessive allele, but when two dominant alleles are present, the phenotype is the result of the expression of both dominant alleles simultaneously. The classic example of co-dominance and multiple alleles is the inheritance of ABO blood groups in humans. Blood type is determined by three different alleles: IA, IB, and i. Only two alleles are present in any single individual, but the population contains all three alleles. IA and IB are both dominant to i. Individuals who are homozygous IA or heterozygous IAi have blood type A; individuals who are homozygous IB or heterozygous IBi have blood type B; and individuals who are homozygous ii have blood type O. However, IA and IB are codominant; individuals who are heterozygous IAIB have a distinct blood type, AB, which combines characteristics of both the A and B blood groups. Co-dominance differs from incomplete dominance because in incomplete dominance the phenotype expressed is a blend of both genotypes. In co-dominance, however, both alleles in the genotype are expressed at the same time without a blending of phenotype.

Conjugation

Conjugation can be described as sexual mating in bacteria; it is the transfer of genetic material between two bacteria that are temporarily joined. A cytoplasmic conjugation bridge is formed between the two cells, and genetic material is transferred from the donor male (+) type to the recipient female (-) type. Only bacteria containing plasmids called sec factors are capable of conjugating. The best studied sex factor is the F factor in E. coli. Bacteria possessing this plasmid are termed F+ cells; those without it are called F- cells. During conjugation between an F+ and an F- cell, the F+ cell replicates its F factor and donates the copy to the recipient, converting it to an F+ cell. Genes that code for other characteristics, such as antibody resistance, may be found on the plasmids and transferred into recipient cells along with these factors. Sometimes the sex factor becomes integrated into the bacterial genome. During conjugation, the entire bacterial chromosome replicates and begins to move from the donor cell to the recipient cell. The conjugation bridge usually breaks before the entire chromosome is transferred, but the bacterial genes that enter the recipient cell can easily recombine with the genes already present to form novel genetic combinations. These bacteria are called Hfr cells, meaning that they have a high frequency of recombination.

Genetics

Genetics is the study of how traits are inherited from one generation to the next. The basic unit of heredity is the gene. Genes are composed of DNA and are located on chromosomes. When a gene exists in more than one formed, the alternative forms are celled alleles. The genetic makeup of an individual is the individual's genotype; the physical manifestation os the genetic makeup is the individual's phenotype. Some phenotypes corresponds to a single genotype, whereas other phenotypes correspond to several different genotypes.

Cytoplasmic Inheritance

Heredity systems exist outside the nucleus. For example, DNA is found in mitochondria and other cytoplasmic bodies. These cytoplasmic genes may interact with nuclear genes and are important in determining the characteristics of their organelles. Drug resistance is many microorganisms is regulated by cytoplasmic DNA, known as plasmids, that contain one or more genes. Plasmids can be passed from one bacterial cell to another via transformation.

Mutation types

In a gene mutation, nitrogen bases are added, deleted, or substituted, thus altering the amino acid sequence. Inappropriate amino acids may be inserted into polypeptide chains, and a mutated protein may be produced. Therefore, a mutation is a genetic "error" with the "wrong" base or missing base in the DNA at any particular position. In a point mutation a nucleic aid is replaced by another nucleic acid. The number of nucleic acids substituted may vary, but generally point mutations involved between one and three nucleotides. There are three possible effects on the codon, the sequence of the three nucleotides that determines the identity of the amino acid. First, the new codon may code for the same amino acid (a silent mutation), and no change in the resulting protein is seen. Second, the new codon may code for a different amino acid (a missense mutation). This may or may not lead to a problem with the resulting protein, depending on the role of that amino acid in determining the protein structure. Finally, the new codon may be a stop codon (a nonsense mutation). Nonsense mutations are often lethal or severely inhibit the functioning of the protein, which can lead to many different problems depending on the role of that protein in organism function. The length of the genome does not change with any of these mutations, but the primary structure of the proteins formed from an RNA sequence with a nonsense mutation could be much shorter due to the premature stop. In a frameshift mutation nucleic acids are deleted or inserted into the genome sequence. This frequently is lethal. The insertion or deletion of nucleic acids throws off the entire sequence of codons from that point on because the genome is "read" in groups of three nucleic acids. Since nucleic acids are inserted or deleted, the length of the genome changes.

Repressible systems

In a repressible system the repressor is inactive until it combines with the co-repressor. The repressor can bind to the operator and prevent transcription only when it has formed a repressor-co-repressor complex. Co-repressors are often the end products of the biosynthetic pathways they control. The proteins produced (usually enzymes) are said to be repressible because they are normally being synthesized.; transcription and translation occur until the co-repressor is synthesized. Operons containing mutations such as deletions or whose regulator genes code for defective repressors are incapable of being turned off; their enzymes, which are always being synthesized, are referred to as constitutive.

Inducible systems

In an inducible system the repressor binds to the operator, forming a barrier that prevents RNA polymerase from transcribing the structural genes. For transcription to occur, an inducer must bind to the repressor, forming an inducer-repressor complex. This complex cannot bind to the operator, thus removing it as a barrier and permitting transcription. The proteins synthesized are thus said to be inducible. The structural genes typically code for an enzyme, and the inducer is usually the substrate, or a derivative of the substrate, upon which the enzyme normally acts. When the substrate (inducer) is present, enzymes are synthesized; when it is absent, enzyme synthesis is negligible. In this manner, enzymes are transcribed only when they are actually needed.

Sex Linkage

In humans, women have two X chromosomes and men have only one. As a result, recessive genes carried on the X chromosome will produce the recessive phenotypes whenever they occur in men because no dominant allele is present to mask them. The recessive phenotype will thus be much more frequently found in men. Examples of sex-linked recessives in humans are the genes for hemophilia and color-blindness. The pattern of inheritance for a sex-linked recessive is somewhat complicated. Because men pass the X chromosome only to their daughters and the gene is carried only on the X chromosome, affected men cannot pass the trait to their mail offspring. Affected men will, however, pass the gene to all of their daughters. Nevertheless, unless the daughter also receives the gene from her mother, she will be a phenotypically normal carrier of the trait. Because all of the daughter's male children will receive their only X chromosome from her, half of her sons will receive the recessive sex-linked allele. Thus sex-linked recessives generally affect only men; they cannot be passed from father to son, but they can be passed from grandfather to grandson via a daughter who is a carrier, thereby skipping a generation.

NON-MENDELIAN INHERITANCE PATTERNS

In most practical applications, inheritance patterns are often more complicated than Mendel would have hoped. One major source of complications is in the relationship between the phenotype and the genotype. In theory, 100 percent of individuals with the recessive phenotype have a homozygous recessive genotype, and 100 percent of individuals with the dominant phenotype have either homozygous or heterozygous genotypes. Such clean concordance between genotype and phenotype is not always the case.

MEDNDELIAN GENETICS

In the 1860s Gregor Mendel developed the basic principals of genetics through his experiments with the garden pea. Mendel studied the inheritance of individual pea traits by performing genetic crosses. He took true-breeding individuals (which, if self-crossed, produce progeny only with the parental phenotype) with different traits, mated them, and statistically analyzed the inheritance of the traits in the progeny.

Dihybrid Cross

In the following example, a purple-flowered tall pea plant is crossed with a white-flowered dwarf pea plant; both plants are doubly homozygous (tall is dominant to dwarf. T= tall allele, t= dwarf allele; purple is dominant to white, P=purple allele, p= white allele). The purple parent's genotype is TTPP, and it thus produces only TP gametes; the white parent's genotype is ttpp and produces only tp gametes. The F1 progeny will all have the genotype TtPp and will be phenotypically dominant for both traits. When the F1 generation is self cross (TtPp x TtPp), it produces four different phenotypes: tall purple, tall white, dwarf purple, and dwarf white, in the ratio 9:3:3:1, respectively. This is the typical pattern for Mendelian inheritance in a dihybrid cross between heterozygotes with independently assorting traits.

Testcross

Mendel also developed the testcross, a diagnostic tool used to determine the genotype of an organism. Only with a recessive phenotype can genotype be predicted with 100 percent accuracy. If the dominant phenotype is expressed, the genotype can be either homozygous dominant or heterozygous. Thus, homozygous recessive organisms always breed true. This fact can be used to determine the unknown genotype of an organism with a dominant phenotype, such as when an organism with a dominant phenotype of unknown genotype (Ax) is crossed with a phenotypically recessive organism. (genotype aa). Since the recessive parent is homozygous, it can donate only the recessive allele, a, to the progeny. If the dominant parent's genotype is AA, all of its gametes will carry an A, and all of the progeny will have the genotype Aa. If the dominant parent's genotype is Aa, half of the progeny will be Aa and express the dominant phenotype, and half will be aa and express the recessive phenotype. In a testcross, the appearance of the recessive phenotype in the progeny indicates that the phenotypically dominant parent is genotypically heterozygous.

Mendel's First Law: Law of segregation

Mendel postulated four principles of inheritance: 1) Genes exist in alternative forms (alleles). A gene controls a specific trait in an organism. 2) An organism has two alleles for each inherited trait, one inherited from each parent. 3) The two alleles segregate during meiosis, resulting in gametes that carry only one allele for any given inherited trait. 4) If two alleles in an individual organism are different, only one will be fully expressed, and the other will be silent. The expressed allele is said to be dominant, the silent allele, recessive. In genetics problems dominant alleles are typically assigned capital letters, and recessive alleles are assigned lowercase letters. Organisms that contain two copies of the same allele are homozygous for that trait; organisms that carry two different alleles are heterozygous. The dominant allele is expressed in the phenotype. This is known as Mendel's law of Dominance. For example, for the genotypes shown below, Yy and YY will both be yellow. YY=Homozygous=Yellow Yy=Heterozygous=Yellow yy=homozyous=green

Drosophila melanogaster

Modern work with the fruit fly (Drosophila melanogaster) helped to provide explanation for Mendelian genetic patters. The fruit fly possess several advantages for genetic research: - It reproduces often (short life cycle) - It reproduces in large numbers (large sample size) - Its chromosomes (especially in the salivary glands) are large and easily recognizable in size and shape. - Its chromosomes are few (4 pairs, 2N=8) - Mutations occur relatively frequently Through genetic and mutational analysis of D. Melanogaster, scientists have elucidated the patterns of embryological development, discovering how genes expressed early in development can affect the adult organism.

Mutagenic agents

Mutagenic agents induce mutations. These include cosmic rays, X-rays, ultraviolet rays, and radioactivity as well as chemical compounds such as colchicine, which inhibits spindle formation, or mustard gas, which alkylates guanine in DNA. Mutagenic agents are sometimes also carcinogenic (cancer-causing).

Mutations

Mutations are changes in the genetic information coded in the DNA of a cell. Mutations that occur in somatic cells can lead to tumors in the individual. Mutations that occur in the sex cells (gametes) will be transmitted to the offspring. Most mutations occur in regions of DNA that do not code for proteins and are silent (not expressed in the phenotype). Mutations that do change the sequence of amino acids in proteins are most often recessive and deleterious.

Nondisjunction

Nondisjunction is either the failure of homologous chromosomes to separate properly during meiosis I or the failure of sister chromatids to separate properly during meiosis II. The resulting zygote might either have three copies of that chromosome, called trisomy (somatic cells will have 2N+ 1 chromosomes), or might have a single copy of that chromosome, called monosomy (somatic cells will have 2N-1 chromosomes). A classic case of trisomy is the birth defect Down syndrome, which is caused by trisomy of chromosome 21. Most monosomies and trisomies are lethal, causing the embryo to spontaneously abort early in the pregnancy. Nondisjunction of the sex chromosomes may also occur, resulting in individuals with extra or missing copies of the X or Y chromosomes.

Punnett Square

One way of predicting the genotypes expected from a cross is by drawing a Punnet square diagram. The parental genotypes are arranged around a grid. Because the genotype of each progeny will be the sum of all alleles donated by the parental gametes, their genotypes can be determined by looking at the intersections on the grid. A Punnett square indicates all the potential progeny genotypes, and the relative frequencies of the different genotypes and phenotypes can be easily calculated. When the F1 generation from out monohybrid cross is self-crossed (i.e., Pp x Pp), the F2 progeny are more genotypically and phenotypically diverse than their parents. Because the F1 plants are heterozygous, they will donate a P allele to half of their descendants and a p allele to the other half. One-fourth (25%) of the F2 plants will have the genotype PP, 50 percent will have the genotype Pp, and 25 percent will have the genotype pp. Because the homozygous dominant and heterozygous genotypes both produce the dominant phenotype purple flowers, 75 percent of the F2 plants will have purple flowers, and 25 percent will have white flowers.

Recombination

Recombination occurs when linked genes are separated. It occurs by breakage and rearrangement of adjacent regions of DNA when organisms carrying different genes or alleles for the same trait are crossed.

Replication

Replication of the bacterial chromosome begins at a unique origin of replication and proceeds in both directions simultaneously. DNA is synthesized in the 5' to 3' direction.

Incomplete Dominance

Some progeny are apparently blends of the parental phenotypes. The classic example is flower color in snapdragons: homozygous dominant red snapdragons when crossed with homozygous recessive white snapdragons, produce 100 percent pink progeny in the F1 generation. When F1 progeny are self-crossed, the produce red, pink, and white progeny in the ration of 1:2:1, respectively. The pink color is the result of the combined effect of the red and white genes in heterozygotes. An allele is incompletely dominant if the phenotype of the heterozygote is an intermediate of the phenotypes of the homozygotes.

BACTERIAL GENETICS- Bacterial Genome

The bacterial genome consists of a single circular chromosome located in the nucleoid region of the cell. Many bacteria also contain similar circular rings of DNA called plasmids, which contain accessory genes. Episomes are plasmids that are capable of integration into the bacterial genome.

Environmental factors

The environment can often affect the expression of a gene. Interaction between the environment and the genotype produces the phenotype. For example, Drosophilia with a given set of genes have crooked wings at low temperatures but straight wings at higher temperatures. Temperature also influences the hair color of the Himalayan hare. The same genes for color result in white hair on the warmer parts of the body and black hair on the colder parts. If the naturally warm portions are cooled (e.g., by the application of ice), the hair will brow in black.

Monohybrid cross

The principles of Mendelian inheritance can be illustrated in a cross between two true-breeding pea plants, one with purple flowers and the other with white flowers. Because only one trait is being studied in this particular mating, it is referred to as a monohybrid cross. The individuals being crossed are the parental or P generation; the progeny generations are the filial or F generations, with each generation numbered sequentially (e.g., F1, F2, etc.). The purple flower parent has the genotype PP (i.e., it has two P alleles) and is homozygous dominant. The white flower parent has the genotype pp and is homozygous recessive. When these individuals are crossed, they produce F1 plants that are 100 percent heterozygous (genotype = Pp). Because purple is dominant to white, all the F1 progeny have the purple flower phenotype.

Gene Regulation

The regulation of transcription, one of the steps of gene expression, enables prokaryotes to control their metabolism. Regulation of transcription is based on the accessibility of RNA polymerase to the genes being transcribed and is directed by an operon, which consists of structural genes, an operator region, and a promoter region on the DNA before the protein coding genes. Structural genes contain sequences of DNA that code for proteins. The operator is a sequence of non-transcribable DNA that is the repressor binding site. The promoter is the noncoding sequence of DNA that serves as the initial binding site for RNA polymerase. There is also a regulator gene, which codes for the synthesis of a repressor molecule that binds to the operator and blocks RNA polymerase from transcribing the structural genes. RNA polymerase must also most past the operator to transcribe the structural genes. Regulatory systems function by preventing or permitting the RNA polymerase to pass on to the structural genes. Regulation may be via inducible systems or repressible systems. Inducible systems are those that require the presence of a substance, called an inducer, for transcription to occur. Repressible systems are in a constant state of transcription unless a co-repressor is present to inhibit transcription.

Mendel's Second Law: Law of Independent Assortment

The segregation principles provides a satisfactory explanation for the inheritance of a single allele and also can be extended to a dihybrid cross, in which the parents differ in two traits, as long as the genes are on separate chromosomes and assort independently during meiosis. Mendel postulated that the inheritance of one such trait is completely independently of any other. In this way, a plant with purple flowers is no more likely to be a dwarf than a plant with white flowers. This is known as Mendel's Law of Independent Assortment. Note that according to modern, non-Mendelian genetics, genes on the same chromosome will not follow this rule and instead will stay together unless crossing over occurs. Nevertheless, crossing over exchanges information between chromosomes and may break the linkage of certain patterns. For example, red hair is usually linked with freckles, but some blondes and brunettes have freckles as well. Generally, the closer the genes are on the chromosome, the more likely they are to be inherited together.

Sex determination

The two members of each of the chromosome pairs are identical in shape except for one pair: the sex chromosomes. Different species vary in their systems of sex determination. In sexually differentiated species most chromosomes exist as pairs of homologues called autosomes, but sex is determined by a pair of sex chromosomes. All humans have 22 pairs of autosomes; additionally, women have a pair of homologous X chromosomes, and men have a pair of heterologous chromosomes, an X and a Y chromosome. The sex chromosomes pair during meiosis and segregate during the first meiotic division. Since female can produce only gametes containing the X chromosome, the gender of a zygote is determined by the genetic contribution of the male gamete. If the sperm carries a Y chromosome, the zygote will be a male; if it carries an X chromosome it will be a female. For every mating, there is a 50 perfect chance that the zygote will be a male or a female. Genes located on the X or Y chromosomes are called sex-linked. In humans, most sex-linked genes are located on the X chromosome, although some Y-linked traits have been found (e.g., hair on the outer ear).

Transformation

Transformation is the process by which a foreign chromosome fragment (plasmid) is incorporated into the bacterial chromosome via recombination, creating new inheritable genetic combinations.