A Code for All Life

A. History of Central Tenets of Genetics 1. Mendel described particulate inheritance. 2. Watson and Crick described nature of the coded instructions. 3. Evolutionary theory is based on common ancestral groups; genetics establishes this lineage. 4. Genes guide the organization and orderly sequence of differentiation. 5. Genetics accounts for resemblance, fidelity of reproduction, and variation. 6. Genetics is a major unifying concept of biology.

B. Mendel s Investigations 1. Gregor Mendel conducted his plant breeding experiments from 1856 1864. 2. His discoveries were published in 1866, but not appreciated until 1900, 16 years after his death. 3. Genes and chromosomes were as yet unknown; his experiments were based on crossbreeding. a. Mendel carefully controlled pollination of pea plant stigmas by stamens. b. Mendel carefully documented offspring of different parents (hybrids) and then crossed the hybrids.

C. Chromosomal Basis of Inheritance 1. Sex cells (gametes) were recognized as providing genetic information to offspring. 2. Nuclei of sex cells, especially chromosomes, were suspected of being the hereditary material. 3. Meiosis: Reduction Division of Gametes a. Animal species differ greatly in the number of chromosomes but, in all species, each body cell has two homologous chromosomes; one from each pair came from each parent. b. In meiosis, a single replication of the genetic material is followed by two rounds of cell division resulting in gametes with one member of each homologous pair. c. Therefore a body cell is diploid (containing two sets of chromosomes), a gamete is haploid (containing a single set), and fertilization results in a diploid zygote.

d. The diploid (2n) number in humans is 46 chromosomes; gametes are haploid with 23. e. In haploid cells, each organism has two genes for each trait, one on each homologous chromosome. f. Alternative forms of a gene are called alleles; one or both may have an effect and either may be passed on to progeny. g. Most unique features of meiosis occur in prophase of first meiotic division. 1) The two members of each pair of homologous chromosomes align side-by-side to form a bivalent. 2) Each chromosome has already replicated to form two chromatids, joined at the centromere.

3) The complex of four future chromosomes is a tetrad. 4) The location of any one gene is the gene locus. 5) In side-by-side contact (synapsis), the gene loci on a chromosome align. 6) In preparation for division, the centromeres holding chromatids together do not divide; the dyads are pulled to each pole. 7) At end of first meiotic division, daughter cells contain one of each homologous chromosome, still joined at centromeres. 8) At end of second meiotic division, dyads are split and each daughter cell contains one haploid set and one allele of each gene.

4. Sex Determination (Figures 5.3, 5.4) a. McClung, in 1902, studied bugs. 1) Half the sperm lacked one chromosome found in the other half and in all eggs. 2) When the sperm with the full number fertilized an egg, a female resulted; when a sperm lacking one chromosome fertilized an egg, it produced a male. 3) Sex chromosomes were those that determined sex; autosomes were the remainder. 4) The bug s sex determination system is called XX-XO indicating the missing chromosome as O.

b. Humans and many others use an XX-XY system; the male has the different sex chromosomes. 1) Half the sperm carry X and half carry Y; they fertilize an X egg to produce 50% of each sex in their offspring. 2) The Y chromosome is smaller than the X and contains fewer genes. c. Birds, moths, butterflies, and some fish use an XX-XY system but the female is the XY. d. Some animals across many taxa use environmental and behavioral conditions rather than sex chromosomes. 1) In crocodiles, turtles and lizards, temperature of the nest determines sex ratio; lower temperatures may produce females, higher produce males. 2) Some fish are hermaphroditic and sensory stimuli trigger male or female development.

5.2. Mendelian Laws of Inheritance A. Mendel s First Law 1. In the law of segregation, during formation of gametes, paired factors segregate independently. a. The phenotype is the visible characteristic. b. Tall and dwarf plants produce tall F1 progeny; hence there is no blending. c. Self-pollinating the F1 progeny produce tall and short in a 3:1 ratio; again there was no blending and this ratio held for crosses of six other traits.

2. Dominance a. Mendel called the tall factor dominant; when it was present the recessive factor is not expressed. b. Recessive traits appear only when both factors are present, a pure condition. c. Capitalized letters represent dominant factors, and the corresponding lower case letter represents the recessive alternative factors. d. T/t represents the complete genetic constitution of the plant s traits for height; T and t are the possible gametes. e. T/t and other unlike combinations form a heterozygote. f. T/T and t/t are homozygotes. g. T/T, T/t and t/t are the possible genotypes. h. A cross involving one pair of contrasting traits is a monohybrid cross. 3. Punnett Square

3. Punnett Square a. Various combinations resulting from available gametes are shown using a Punnett square. b. This allows a T/t x T/t cross to represent the 3:1 ratio. c. Additional crosses of the progeny demonstrated that onethird of the tall was TT and two-thirds were T/t. d. The short plants, or t/t, always gave rise to short plants when self-fertilized. 4. Testcross a. Products of a monohybrid cross have T/t individuals hidden among the T/T. b. To reveal them, a testcross mates each with a pure recessive. c. If homozygous (T/T), the testcross yields all tall. d. If heterozygous (T/t), the testcross yields half tall and half short.

5. Intermediate Inheritance (Figure 5.5) a. Sometimes, neither allele is completely dominant, resulting in intermediate inheritance or incomplete dominance. b. Red and white homozygous four-o-clock flowers cross to form heterozygous pink flowers. c. Chickens with black feathers crossed with splashed white feathered chickens yield blue Andalusian chickens. d. This appears to produce a blending of traits, but additional crosses will reveal the traits are present and still able to be expressed with the appropriate testcross.

B. Mendel s Second Law (Figure 5.6) 1. The law of independent assortment states that genes located on different pairs of homologous chromosomes assort independently during meiosis. a. This deals with two different characters on two different chromosomes. b. When tall plants with yellow seeds (both dominant traits) were crossed with dwarf plants with green seeds, the F1 plants were all tall and yellow as expected. c. When the F1 hybrids were self-fertilized, a 9:3:3:1 ratio resulted, which is a combination of the two 3:1 ratios for each set or a dihybrid cross. d. Segregation of alleles for heights was independent of segregation of alleles for seed color.

2. Probability a. All genotypes of gametes of one sex have an equal chance of uniting with all genotypes of gametes of the other sex. b. The probability of two independent events occurring together is the product of their individual probabilities; this is the product rule. (Table 5.1) c. Probability has no memory.

C. Multiple Alleles 1. While only two alleles can exist at one locus, more than two types of alleles may exist in a population. 2. For instance, rabbits may possess two alleles from among four for coat color: C (normal), cch (chinchilla), ch (Himalayan) and c (albino). 3. Multiple alleles arise through mutations at the same locus over time.

D. Gene Interaction 1. Many different genotypes may affect a single phenotype. 2. Many genes have more than one effect (i.e., eye color and other features). 3. An allele at one location that masks expression of an allele at another locus acting on the same trait is called epistasis. 4. Several sets of alleles may produce a cumulative effect on the same character. 5. Polygenic characters show continuous variation between extremes (blending or quantitative inheritance); skin pigmentation in humans probably involves 3 or 4 genes.

E. Sex-Linked Inheritance (Figures 5.7, 5.8, 5.9) 1. Some traits depend on the sex of the parent carrying the gene. a. Hemophilia is a recessive trait on the X chromosome. b. Red-green color blindness is also a recessive trait and on the X chromosome. c. Carriers are heterozygous for these genes and are phenotypically normal.

2. The inheritance pattern is unique. a. The X-linked trait is expressed when both are recessive in a female but only one is present in a male. b. When the mother is a carrier and the father is normal, half of the sons are affected. c. It is more prevalent in males because a single sex-linked recessive gene in the male has a visible effect.

3. In fruit flies, the gene for eye color is carried on the X chromosome. a. When white-eyed males are crossed with red-eyed females, the F1 have red eyes. b. When the F1 is crossed, all F2 females have red eyes, half the males have red eyes and half have white eyes. c. Males are hemizygous for traits carried on the X chromosome.

F. Autosomal Linkage and Crossing Over 1. Linkage a. Not all factors segregate as stated in Mendel s second law. b. Genes on the same chromosome are linked, and the traits are inherited together. 2. Traits on the same chromosome are coded as letters without a slash mark (i.e., AB/ab).

3. Crossing Over (Figure 5.10) a. Linkage is not absolute; some separation of alleles on the same chromosome occurs due to crossing over. b. During protracted prophase of meiosis I, some paired homologous chromosomes break and exchange equivalent portions. c. Crossing over exchanges genes between homologous pairs with great frequency; crossing over occurs nearly 100% each meiotic cycle for longer chromosomes. d. The more distant the loci, the more likely a break will intervene. e. The variation in crossing over allows mapping of genes on chromosomes.

G. Chromosomal Aberrations 1. Structural and numerical deviations from the norm that affect many genes are chromosomal aberrations. 2. It is estimated that five of every 1,000 humans are born with a serious genetic defect from chromosomal anomalies. 3. Euploidy is the addition or deletion of whole sets of chromosomes; polyploidy is most common in plants but animals cannot tolerate this type of chromosomal aberration. 4. Aneuploidy is the addition or deletion of a single chromosome. a. It is usually caused by failure of chromosomes to separate during meiosis (nondisjunction). b. This results in one gamete having an extra chromosome and one lacking a chromosome. c. The monosomic animal (n-1) rarely survives due to uneven balance of genetic instructions. d. Trisomy (n+1) is more common; trisomy 21 or Down syndrome has an extra 21st chromosome.

5. Structural aberrations involve whole sequences of genes within a chromosome. a. Inversions reverse the order of a segment of genes. b. Translocation is the movement of a section of genes. c. Deletion is loss of a block of genes. d. Duplication adds an extra section of chromosome; they may add additional genetic information and allow new functions. 6. Genetic Nondisjunction and Syndromes: Klinefelter syndrome and Turner syndrome are the result of genetic nondisjunction. - genetic nondisjunction is the failure of chromosome to separate during meiosis

5.3. Gene Theory A. Gene Concept 1. W. Johannsen coined the term gene in 1909 to name the hereditary factors referred to by Mendel. a. Originally, genes were considered indivisible units. b. Alleles are now known to be divisible by recombination; portions are separable. c. Parts of eukaryote genes are separated by introns, which are sections of DNA that do not specify a product.


One Gene One Enzyme Hypothesis

1. Since genes produce different phenotypes and expression appears to follow: gene > gene product > phenotypic expression. 2. Gene products are usually proteins; proteins act as enzymes, antibodies, hormones and structures. 3. Research with the bread mold Neurospora associated genes with enzymes. a. They were haploid and unaffected by dominance, and irradiation easily induced mutations. b. Each mutant strain resulted in one defective enzyme; this discovery earned Beadle and Tatum the Nobel Prize in 1958.

c. This describes the cause of hundreds of inherited disorders based on missing enzymes. d. However not all proteins specified by genes are enzymes, etc. and some genes direct synthesis of transfer RNA. e. A gene is now defined more inclusively as a nucleic acid sequence that encodes a functional polypeptide or RNA sequence.


Storage and Transfer of Genetic Information (Figures 5.11 5.16

A. Nucleic Acids: Molecular Basis of Inheritance 1. Nucleotides a. Both DNA and RNA are polymers built of nucleotides. b. Each nucleotide contains a sugar, a nitrogenous base and a phosphate group. c. The DNA s sugar is deoxyribose, and RNA contains a ribose 5-carbon sugar. d. Nitrogenous bases are either pyrimidines (6-membered ring) or purines (two fused rings). e. Purines in both DNA and RNA are adenine and guanine. f. Pyrimidines in DNA are thymine and cytosine; in RNA they are uracil and cytosine. g. The DNA backbone is built of phosphoric acid and deoxyribose.

h. The 5' end of the backbone has a free phosphate group on the 5' carbon of the ribose and the 3' end has a free hydroxyl group on the 3' carbon. i. DNA is two complementary chains precisely cross-linked by specific hydrogen bonding between purine and pyrimidine bases. j. The number of adenines is equal to thymines, and guanines equal cytosines suggesting that these bases are paired. k. The DNA ladder is twisted into a double helix; ten base pairs occur per turn. l. The two DNA strands are antiparallel; the 5' end of one is bonded to the 3' end of the other. m. Strands are complementary; sequence of bases of one strand specifies the sequence of the other.

Pentose Sugars of Nucleic Acids

Section of DNA Strand

Position of hydrogen bonds

Complementary pairing of Bases between the sugar Phosphate backbones

DNA molecule

n. RNA is similar to DNA except it has a single polynucleotide chain, has ribose instead of deoxyribose, and has uracil instead of thymine. o. DNA is replicated precisely in daughter cells; each strand is a template for the new complementary strand. p. Ribosomal, transfer, and messenger RNAs are the most abundant and well-known types of RNA, but many structural and regulatory RNAs, such as micro RNAs, have been reported

2. DNA Coding by Base Sequence (Figure 5.17) a. The DNA coding sequence is collinear with the sequence of amino acids in a protein. b. Four bases cannot code for 20 amino acids if taken in 1:1 correlation. c. Sequences of 3 bases provides 64 (43) combinations, enough to code for the amino acids. d. Later work confirmed the triplet codons with redundancy. (Table 5.3) e. DNA is stable but subject to chemical and radiation damage. f. Excision repair uses enzymes to separate pyrimidines covalently bonded by UV radiation.

g. DNA polymerase synthesizes the missing strand according to base-pairing rules. h. DNA ligase joins the end of the new strand to the old one. i. DNA polymerase only synthesizes new strands in the direction of 5' to 3'. j. The parent DNA strands are antiparallel, so synthesis along one of the strands is continuous, and the other is performed in a series of fragments running 5' to 3'.

Replication of DNA


Transcription and the Role of Messenger RNA (Figures 5.18, 5.19

a. DNA codes for proteins but does not participate directly in protein synthesis. b. An intermediary, messenger RNA (mRNA) is used. c. DNA is transcribed into mRNA with uracil substituting for thymine. (Table 5.3) d. RNA polymerase makes a complementary copy of one strand of DNA to form mRNA. e. A different RNA polymerase is used to produce ribosomal, transfer and messenger RNA.

f. Only one of the two DNA strands, the sense strand, is used as a template for RNA synthesis. The strand not used as a template is called the antisense strand. g. Genes were thought to be continuous stretches of DNA until introns, sections that do not code for a product, were discovered. h. Genes coding for many proteins may be discontinuous; genes coding for histones and interferon are continuous. i. Some genes are rearranged during development to code for different proteins. j. Some RNA can self-catalyze the excision of introns; since it changes in the reaction, this is not technically an enzyme.

4. Translation: Final Stage in Information Transfer (Figures 5.20 5.22) a. Translation takes place on ribosomes composed of protein and ribosomal RNA (rRNA). b. Ribosomal RNA has a large and small subunit; together they form a functional unit. c. The mRNA attaches to ribosomes often many in a row to form a complex called a polyribosome or polysome. d. Several molecules of the same protein can then be synthesized at once, one per ribosome.

e. Assembly of proteins requires large transfer RNA molecules. f. The tRNA collects free amino acids and delivers them to the polysome. g. There is a unique tRNA for each amino acid. h. Each tRNA has a specific tRNA synthetase to sort and attach amino acid to the end of each tRNA, called charging. i. On the tRNA, a sequence of three bases (anticodon) forms base pairs with complementary bases (codon) in mRNA. j. The anticodon of tRNA correctly sequences the amino acids to build the protein.

5. Regulation of Gene Expression (Figure 5.23) a. As tissues differentiate, they use only certain sections of genetic material. b. Most genes are inactive at any one time; therefore timing is critical to normal function. c. Transcriptional Control 1) Transcription factors are molecules that have a positive or negative effect on transcription of RNA from DNA. 2) Steroid hormones enter the cell and bind with a receptor protein in the nucleus; this complex binds with DNA near the target gene. 3) Progesterone binds with a nuclear receptor in oviduct cells; this activates transcription of genes encoding egg albumin.

d. Translational Control 1) Genes are transcribed but mRNA is sequestered so translation is delayed. 2) Egg development is often held back; large amounts of messenger RNA accumulate until fertilization activates metabolism and translation of maternal mRNA. e. Gene Rearrangement 1) Rearrangement of DNA sequences coding for antibodies, which allows for vast diversity. f. DNA Modification 1) Methylation of cytosine residues turns genes off. 2) This occurs when cytosine is next to a guanine residue; when DNA is replicated, an enzyme recognizes the CG sequence and methylates the daughter strand.

B. Molecular Genetics 1. Recombinant DNA (Figure 5.24) a. Restriction endonucleases are enzymes derived from bacteria. b. They cleave double-stranded DNA at particular sites, leaving sticky ends. c. Combined with others, they join by rules of complementary base pairing. d. They are sealed together by DNA ligase. e. If the joined DNA is from different sources, this constitutes recombinant DNA. f. Plasmids and bacteriophages that carry recombinant DNA are vectors

2. Polymerase Chain Reaction (Figure 5.25) a. If a gene sequence is known, it can be cloned using polymerase chain reaction. b. Short chains of nucleotides called primers, complementary to the sequence, are synthesized. c. Added to the DNA, the mixture is heated to separate the DNA, and cooled. d. DNA polymerase and the four deoxyribonucleotide triphosphates are added; DNA synthesis proceeds from the 3' end of each primer. e. Entire strands are synthesized as the heat-cool cycle is repeated. f. At five minutes per cycle, less than 2 hours is needed to yield a million copies of one strand.

Steps in the Polymerase Chain reaction

5. Genomics and Proteomics a. Mapping, sequencing and analyzing genomes is genomics. b. The task of mapping the human genome, originally expected to take until the year 2700, is now complete. c. Mapping is completed or nearly completed on many organisms such as bacteria, yeast, fruit flies and nematodes. d. The human genome is much smaller than previously thought, now estimated at about 40,000 protein-encoding genes. e. There are about 740 gene codes for RNAs; about 90% of sequences in euchromatin (gene-rich portions of chromosomes,contrasted with heterochromatin, areas where there are few genes).

f. g.

h. i. j. k. L.

Only about 5% of the 28% actually transcribed into RNA encoded protein. More than half the DNA present is repeated; sequences of several types, including 45% in parasitic DNA elements ( junk or selfish DNA) DNA that seems to serve no function save its own propagation. Nearly 1000 human diseases, such as cystic fibrosis and Huntington s chorea, result from defects in single genes. Almost 300 disease-associated genes have already been identified. The human genome of some 40,000 genes is responsible for hundreds of thousands of different proteins. A single gene can, by some means, give rise to many differing proteins. Scientists in the field of proteomics are trying to determine how proteins interact to accomplish their functions, and to outline the folding structure of proteins.

C. Sources of Phenotypic Variation 1. There are several sources of variation. a. Independent assortment of chromosomes, crossing over and random fusion of gametes reshuffle and amplify the genetic material present. b. Gene mutations and chromosomal aberrations provide new genetic variation. 2. Gene Mutations a. Chemical or physical changes in genes result in alteration of the sequence of bases in DNA. b. A codon substitution results in incorrect amino acids causing sickle cell anemia. c. Once a gene is mutated, it faithfully reproduces itself. d. The environment imposes a screening process (natural selection) that continues the beneficial and eliminates the harmful. e. A population carries a reservoir of mutations unexpressed in heterozygotes

Frequency of Mutations a. A long gene is more likely to have a mutation than a short gene. b. Every person carries approximately one new mutation; most are recessive and not expressed. 4. Molecular Genetics of Cancer 5. Oncogenes and Tumor Suppressor Genes 1.Cancer is a result of a series of specific genetic changes that take place in a particular clone of cells. 2. These changes may include alterations of oncogenes and tumor suppressor genes 3. Normally, oncogenes are in the form of proto-oncogenes 4. One proto-oncogene code for the protein Ras (a guanosine triphosphatase GTP-ase is located just beneath the cell membrane). 5. When a receptor on the cell surface binds a growth factor, Ras is activated and initiates a cascade of reactions, ultimately leading to cell division.

6. Cellular DNA can sustain damage largely by ionizing radiation, ultraviolet radiation, and chemical mutagens, all of which may result in free radicals with unpaired electrons. 7. Some damaged DNA can be repaired. 8. Gene products such as p53 (for 53-kilodalton protein ) are tumor suppressors that act on cell proliferation.

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