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Heredity

Heredity and Evolution


Meiosis and gametogenesis
Hereditary Similarity and Variation Hereditary/inheritance-the transmission of traits from one generation to the next Variation-offspring differ somewhat in appearance from parents and siblings. Genetics- scientific study of heredity and hereditary variation. Offspring acquire genes from parents by inheriting chromosomes Genes- hereditary units (segments of DNA) which parents endow their offspring. Accounts for genetic links and family resemblances. Inherited information is passed on in the form of each genes specific sequence of nucleotides. Most genes program cells to synthesize specific enzymes and other proteins whose cumulative action produces an organisms inherited traits. (This is in the form of DNA) Gametes- vehicles that transmit genes from one generation to the next During fertilization, male and female gametes (Sperm and eggs) unite, thereby passing on the genes of both parents to their offspring Locus- genes specific location along the length of a chromosome: Our genetic endowment consists of the genes carried on the chromosomes we inherited from our parents. Asexual and Sexual Reproduction Asexual reproduction: a single individual is the sole parent and passes copies of all its genes to its offspring. The genomes of the offspring are identical to parents genome An individual that reproduces asexually gives rise to a clone- a group of genetically identical individual. Sexual reproduction: two parents give rise to offspring that have unique combinations of genes inherited from the two parents. Offspring vary genetically from their siblings and both parents

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Fertilization and meiosis alternate in sexual life cycles A life cycle: generation-to-generation sequence of stages in the reproductive history of an organism, from conception to production of its own offspring. Somatic cells (non-sex cell)- has 46 chromosomes. Karyotype- resulting ordered display after chromosomes are arranged in pairs starting with the longest chromosome. Homologous chromosomes- two chromosomes composing a pair that has the same length, centromere position and staining mologues. Both chromosomes of each pair carry genes controlling the same inherited characters. X and Y-chromosomes are sex chromosomes. Other chromosomes are called autosomes. We inherit one chromosome of each pair from each parent; so the 46 chromosomes in our somatic cells are actually two sets of 23 chromosomes-a maternal sets and a paternal set. Any cell with two chromosome sets if called a diploid cell and has a diploid number of chromosomes. (2n) For humans- the diploid number is 46 (2n = 46) Gametes contain a single chromosome set. Such cells are haploid cells (n). For humans- the haploid number is 23 (n = 23) The set of 23 consists of 22 autosomes and 1 single sex chromosome o An unfertilized egg cell contains an X chromosome. A sperm cell contains an X or a Y chromosome. Behavior of Chromosome sets in the human life cycle Fertilization- haploid sperm cell from the father fuses with a haploid ovum from mother. This union of gametes, culminating in fusion of their nuclei. The resulting fertilized egg, or zygote is diploid because it contains two haploid sets of chromosomes bearing genes representing the maternal and paternal family lines. The only cells of the human body not produced by mitosis are the gametes. The variety of sexual life cycles Life cycles differ in the timing of meiosis in relation to fertilization. Multicellular organisms may be diploid or haploid or may alternate between haploid and diploid generations. Humans and most other animals:

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! Gametes are the only haploid cells. Meiosis occurs during the production of gametes, which undergo no further cell division prior to fertilization. The diploid zygote divides by mitosis, producing a multicellular organism that is diploid Plants and some species: Alternations of generations- include both diploid and haploid multicellular stages. The multicellular diploid stage is called the sporophyte Meiosis in the sporophyte produces haploid cells called spores. o A spore gives rise to a multicellular individual without fusing with another cell. o A spore divides mitotically to generate a multicellular haploid cell called the gametophyte. Fungi and some protists: After gametes fuse and form a diploid zygote, meiosis occurs without a diploid offspring developing. (Meiosis produces haploid cells that then divide by mitosis and give rise to haploid multicellular organism. Meiosis reduces the number of chromosome sets from diploid to haploid. Meiosis I and Meiosis II results in four daughter cells, each with only half as many chromosomes as the parent cell. Interphase: chromosomes replicate but remain uncondensed. Each replicated chromosome consists of two genetically identical sister chromatids connected at the centromere. The centrosome replicated forming two centrosomes Prophase I: chromosomes begin to condense. Homologous chromosomes loosely pair along their lengths, precisely aligned gene by gene. Crossing over: the DNA molecules in nonsister chromatids break at corresponding places and rejoin to the others DNA The movement of centrosomes, formation of spindle microtubules. Breakdown of the nuclear envelope and dispersal of nucleoli Metaphase I: pair of homologous chromosomes is arranged on metaphase plate with one chromosome of each pair facing each pole. Both chromatids of a homologue are attached to kinetochore microtubules from one pole. And same for other side. Anaphase I: chromosomes move towards poles, guided by spindles. Sister chromatids remain attached at the centromere and move as a single unite toward the same pole. Homologous chromosomes each composed of two sister chromatids, move towards opposite poles.

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! Telophase I and Cytokinesis: at the beginning of telophase, each half of the cell has a complete haploid set of chromosomes but each chromosome is still composed of two sister chromatids. Two haploid daughter cells are formed Cleavage furrow/plant cell wall begins to form Chromosomes decondense and the nuclear envelope and nucleoli reform. Prophase II: spindle apparatus forms Chromosomes each still composed of two chromatids move towards metaphase plate Metaphase II: chromosomes are positioned on metaphase plate Because of previous crossing over (in meiosis I), the two sister chromatids of each chromosome are not genetically identical. Anaphase II: centromere of each chromosome finally separate and the sister chromatids come apart. The sister chromatids of each chromosome now move as two individual chromosomes towards opposite poles. Telophase II and Cytokinesis: nuclei form and the chromosomes begin decondensing. The meiotic division of one parent cell produces four daughter cells, each with a haploid set of chromosomes. o Each daughter cell is genetically distinct from the other daughter cells and from the parent cell A comparison of Mitosis and Meiosis Meiosis is distinguished from mitosis by three events of meiosis I: Synapse (crossing over)- genetic rearrangement between nonsister chromatids. Positioning of paired homologous chromosomes on the metaphase plate, rather than individual replicated chromosomes. Movement of two chromosomes of each homologous pair to opposite poles during Anaphase I. Genetic Variation produced in sexual life cycles contributes to evolution. Origins of Genetic Variation Among Offspring The events of sexual reproduction that contribute to genetic variation in a population are independent assortment of chromosomes during meiosis, crossing over during meiosis I and random fertilization of egg cells by sperm. Independent Assortment- because each homologous pair of chromosomes is positioned independently of the other pairs at metaphase I, the first meiotic division results in each pair sorting its maternal and paternal homologues into daughter cells independently of every other pair.

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! Crossing Over- produces recombinant chromosomes-individual chromosomes that carry genes DNA derived from two different parents. Random Fertilization- adds to the genetic variation arising from meiosis. In humans each male and female gamete represents one of approximately 8 million possible chromosome combinations; this is due to independent assortment during meiosis.

Evolutionary Significance of Genetic Variation within populations Average, those individuals best suited to the local environment leave the most offspring, thus transmitting their genes. Genetic variation is the raw material for evolution by natural selection. Mutations are the original source of this variation. The production of new combination of variant genes in sexual reproduction generate additional genetic diversity.

Eukaryotic chromosomes
Chromatin structure is based on successive levels of DNA packaging Nucleosomes or Beads of a String: Histones (proteins) have a high proportion of positively charged amino acids and they bind tightly to negatively charged DNA. Unfolded chromatin appears as beads of a string. Each bead is a nucleosome. Each string is called a linker DNA. o Nucleosome: basic unit of DNA packaging. Association of DNA and histones in nucleosomes seems to remain intact throughout cell cycle. The histones leave the DNA only transiently during DNA replication. Higher Levels of DNA packaging Interactions between the histone tails of one nucleosome and the linker DNA and the nucleosomes to either side. Additional folding leads ultimately to the highly condensed chromatin of the metaphase chromosome. In interphase cells, most chromatin is less compacted (euchromatin) but some remain highly compacted (heterochromatin) o Heterochromatin: heterochromatin DNA is largely inaccessible to transcription enzymes and is therefore not generally transcribed. o Euchromatin: makes its DNA accessible to enzymes and available for transcription.

Gene expression can be regulated at any stage, but the key step is transcription:

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! During development of a multicellular organism, its cells undergo a process of specialization in form and function called cell differentiation resulting in several or many different cell types. Differential gene expression: differences between cell types are due to differential gene expression: the expression of different genes by cells with the same genome In each type of differentiated cell, a unique subset of genes is expressed. Key stages at which gene expression may be regulated include changes in chromatin structure, initiation of transcription, RNA processing, mRNA degradation, translation and protein processing ad degradation Chromatin structure helps regulate gene expression. Genes within heterochromatin (highly condensed) are usually not expressed/transcribed. Chemical modification of histone tails can affect the configuration of chromatin and thus gene expression. Histone acetylation seems to loosen chromatin structure and thereby enhance transcription o Histone code hypothesis: specific combinations of modifications help determine the chromatin configuration, which in turn influences transcription. DNA methylation is associated with reduced transcription. Epigenetic Inheritance: inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence Chromatin-modifying enzymes provide initial control of gene expression by making a region of DNA either more or less able to bind the transcription machinery. Control elements: segments of noncoding DNA that help regulate transcription by binding certain proteins. There control elements and the proteins they bind are critical to the precise regulation of gene expression seen in different cell types. To initiate transcription, eukaryotic RNA polymerase requires transcription factors. o General transcription factors: only a few independently bind a DNA sequence. Example: TATA box within the promoter. The other bind proteins including each other and RNA polymerase II. ! Proximal control elements: located close to the promoter. ! Enhancers: More distant distal control elements ! Activator: protein that binds to an enhancer and stimulates transcription of a gene. ! Repressors: can cause inhibition of gene expression in several different ways. Certain repressors block the binding of activators either to their control elements or to components of the transcription machinery.

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! The particular combination of control elements in an enhancer associated with a gene turns out to be more important that the presence of a single unique control element in regulation transcription in a gene

Coordinate control of dispersed genes in a eukaryotic cell often occurs in response to external chemical signals. Many signal molecules bind to receptors on a cells surface and never enter the cell. This can control gene expression indirectly by triggering signal transduction pathways. RNA processing in the nucleus and export of mature RNA to the cytoplasm provides several opportunities for regulating gene expression that are not available in prokaryotes. Alternative RNA splicing: different mRNA molecules are produced from the primary transcript. Regulatory proteins specific to a cell type control intronexon choices by binding to regulatory sequences. Enzymes degrade prokaryotic mRNA molecules within a few minutes of their synthesis. mRNA is broken down due to enzymatic shortening of the polyA tail and then the 5 nucleotide cap. o microRNAs: Small single stranded RNA molecules bind to complementary sequences in mRNA molecules. These are formed by longer RNA precursors that fold back on themselves forming a long, double stranded hairpin structure. An enzyme called a Dicer then curs the double stranded RNA molecule into short fragments. o Small interfering RNAs (siRNAs): is believed to have originated as a defense against infection by RNA viruses. The initiation of translation of selected mRNAs can be blocked by regulatory proteins that bind to specific sequences or structures within the untranslated region at the 5 end of mRNA preventing the attachment of ribosomes Cell surface proteins and many others must also be transported to target destination in the cell in order to function. Regulation might occur at any of the steps involved in modifying or transporting a protein. Selective degradation: some proteins are involved in time regulation. o Proteasomes: giant protein complexes recognize the ubiquitin tagged protein molecules and degrade them. Cancer results from genetic changes that affect the cell cycle control. Genes that regulate cell growth and division during cell cycle includes genes for growth factors, their receptors and the intracellular molecules of signaling pathways. Mutations that alter any of these genes in somatic cells can lead to cancer. All tumor viruses transform cells into cancer cells through the integration of viral nucleic acid into host cell DNA. Oncogenes: cancer causing genes. These were found in the genomes of humans and other animals.

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! Pro-oncogenes: normal cellular genes- code for proteins that stimulate normal cell growth and division. Oncogenes arise from a genetic change that leads to an increase in the amount of the proto-oncogenes protein product or activity of each protein molecule. The genetic changes that convert proto-oncogenes to oncogenes are: o The movement of DNA within the genome o The amplification of a proto-oncogene o Point mutations in a control element or in a proto-oncogene. ! Either in the promoter or enhancer that controls a protooncogene. ! In the coding sequence, changing the genes product to a protein. Cancer cells are found to contain chromosomes that have broken and rejoined incorrectly, translocating fragments from one chromosome to another. If a translocated proto-oncogene ends up near an active promoter, its transcription may increase, making it oncogene. Tumor suppressor genes: genes whose normal products inhibit cell division" proteins they encode help prevent uncontrolled cell growth.

Interference with normal cell signaling pathways: Many proto-oncogenes and tumorsuppressor genes encode components of growth-stimulating and growth-inhibiting signaling pathways. A hyperactive version of a protein in a stimulatory pathway such as Ras (a g protein) functions as an oncogene protein. A transcriptase activator fails to function as a tumor suppressor. Ras protein encoded by the ras gene is a G protein that relays a signal from a growth factor receptor on the plasma membrane to a cascade of protein kinases. This triggers the synthesis of a protein that stimulates the cell cycle. o Certain mutations can lead to the production of a hyperactive Ras protein: this will result in increased cell division even in the absence of a growth factor. P53 gene: when activated the gene functions as an activator for several other genes P21: halts the cell cycle by binding to cyclin dependent kinases. A multistep model of cancer development: normal cells are converted to cancer cells by the accumulation of multiple mutations affecting proto-oncogenes and tumor-suppressor genes. Certain viruses promote cancer by integration of viral DNA into a cells genome. Eukaryotic genomes can have many noncoding DNA sequences in addition to genes The relationship between genomic composition and organismal complexity Compared with prokaryotic genomes, the genomes of eukaryotes generally are larger, have longer genes, and contain a much greater amount of noncoding DNA both associated with genes and between genes.

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! Transposable Elements and Related Sequences: The most abundant type of repetitive DN in multicellular eukaryotes consists of transposable elements and related sequences. Two types of transposable elements occur in eukaryotes Transposons: move via a DNA intermediate Retrotransposons: move via a ENA intermediate Each element may be hundreds or thousands of base pair long, and similar but usually not identical copies are dispersed throughout the genome. Other repetitive DNA, including simple sequence DNA: Short noncoding sequences that are repeated thousands of times (simple sequence DNA) are especially prominent in centromeres and telomeres, where they probably play structural roles in the chromosome. Genes and Multigene Families: most eukaryotic genes are present in one copy per haploid set of chromosomes. However, the transcription unit encoding the three largest rRNAs is repeated hundreds to thousands of times at one or several chromosomal sites" enabling the cell to make the rRNA for ribosomes. Different genes in the two-globin gene families encode polypeptides used at different developmental stages of an animal. Duplications, rearrangements and mutations of DNA contribute to genome evolution Duplication of Chromosome Sets: accidents in cell division can lead to extra copies of all or part of a genome, which may then diverge if one set accumulates sequence changes. Duplication and Divergence of DNA segments: the genes encoding the various globin proteins evolved from one common ancestral globin gene which duplicated and diverged into alpha globin and beta globin ancestral genes. Subsequent duplications of these genes and random mutations gave rise to the present globin genes, all of which code for oxygen binding proteins. The copies of some supplicated genes have diverged so much during evolutionary time that the functions of their encoded proteins are now different Rearrangements of Parts of Genes: Exon Duplication and Exon Shuffling Rearrangements of exons within and between genes during evolution has led to genes containing multiple copies of similar exons derived from other genes How Transposable Elements contribute to genome evolution Movement of transposable elements or recombination between copies of the same element occasionally generates new sequence combinations hat are beneficial to the organism. Such mechanisms can alter the functions of genes or their patterns of expression and regulation.

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Mendel and the Gene Idea


The gene idea- parents pass on discrete heritable units-genes-that retain their separate identities in offspring. Mendel uses the scientific approach to identify two laws of inheritance -By breeding garden peas in carefully planned experiments. Mendels experimental, quantitative approach Two professors were influential: Physicist Christian Dippler: encouraged students to learn science through experimentation and trained Mendel to use mathematics to help explain natural phenomena. Botanist Franz Unger: aroused Mendels interest in the causes of variation in plants. Why did Mendel use peas? they are available in many different varieties. Could strictly control which plants mated with which. The reproductive organs of a pea plant are in its flowers and each pea flower has both pollen-producing organs(stamens) and egg bearing organs(carpel). Character- a heritable feature,(such as flower and color) that varies among individuals. Trait- each variant of a character (such as purple or white color) True-breeding: dominance(NN/Nn)purple plant produce only purple. o Hybridization: the mating or two tree breeding varieties o True breeding parents are the P Generation ! Their hybrid offspring is the F1 Generation ! F1 reproduce to make F2 generation

The law of segregation The law states that the two alleles of a gene separate during gamete formation so that a sperm/egg carries only one allele of each pair. Mendel proposed this law to explain the 3:1 ratio (F2phenotypes) Genes have alternative forms and each organism inherits one allele for each gene from each parent. Allele: alternative versions of genes accountable for variations in inherited characters. o Dominant allele: determines the organisms appearance o Recessive allele: has no noticeable effect on organisms appearance. Homozygous individuals: have identical alleles of a given gene and are truebreeding Heterozygous individuals: have two different alleles of a given gene. Genotype: genetic makeup Phenotype: organisms traits "#$%$&'!()*+,!-./#.0!

The law of Independent Assortment this law states that each pair of alleles segregates into gametes independently of other pairs. Mendel proposed this law based on the dihybrid crosses between plants heterozygous for both genes. The offspring of a dihybrid cross (F2 generation) have four phenotypes: 9(NN):3(Nn): 3(nN):1(nn) Monohybrids: heterozygous for one character Dihybrids: heterozygous for both characters (YyRr) Laws of probability govern Mendelian inheritance The Multiplication and Addition Rules applied to monohybrid crosses The multiplication rule states that the probability of a compound event is equal to the produce of the individual probabilities of the single event o !x!=" The addition rule states that the probability of n event that can occur in two or more independent, mutually exclusive ways is the sum of the individual probabilities o !+ " = # Solving complex genetics problems with the rules of probability A dihybrid cross is equivalent to two or more independent monohybrid crosses occurring simultaneously. Each character is considered separately and then the individual probabilities are multiplied together

Inheritance patterns
Inheritance patterns are often more complex that predicted by simple Medelian genetics. Spectrum of Dominance-different degrees of dominance and recessiveness Complete dominance: one allele over another (NN or Nn); the phenotypes of the heterozygotes (Nn) and dominant homozygote (NN) are distinguishable. Codominane: both alleles affect the phenotype in separate distinguishable ways. Both genes are expressed in heterozygotes Incomplete dominance: no dominance of either allele. Provides evidence for the blending hypothesis of inheritance. The heterozygote phenotype is intermediate between the two homozygous phenotypes. Pleiotrophy: the ability of a single gene to affect multiple phenotypic characters "#$%$&'!()*+,!-./#.0!

! Tay-Sachs disease-an inherited disorder in humans. The brain cells of a baby are unable to metabolize certain lipids because a crucial enzyme does not work properly. Lead to seizures, blindness and degeneration of motor and mental performance. Multiple alleles: most genes actually exist in populations in more than two allelic forms. ABO blood groups of humans; there are four possible phenotypes: A, B, AB or O.

Extending Mendelian genetics for two or more genes Epistasis: a gene at one locus alters the phenotype expression of a gene at a second locus. Polygenic inheritance: a single phenotypic character is affected by two or more genes; characters influenced by multiple genes are often quantitative( they vary continuously). Nature and Nurture: the environmental impact on phenotype The genotype generally is not associated with a rigidly defined phenotype, but rather with a range of phenotypic possibilities due to environmental influences. Norm of Reaction: phenotypic range for genotype Multifactorial: meaning that many factors both genetic and environmental collectively influence phenotype Integrating a Mendelian view of heredity and variation An organisms overall phenotype, including physical appearance, internal anatomy, physiology, and behavior reflects its overall genome and unique environment history. Phenotype: refer not only to specific characters but also to an organisms entirety: all aspects of its physical appearance, internal anatomy, physiology, and behavior Genotype: refer to an organisms entire genetic makeup, not just its alleles. Many human traits follow Mendelian patterns of inheritance Pedigree Analysis: used to deduce the possible genotypes of individuals and make predictions about future offspring. Predictions are usually statistical probabilities rather than certainties.

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Recessively Inherited Disorders: thousands of genetic disorders are known to be inherited by simple recessive traits. (Albinism, cystic fibrosis, sickle cell) Many affected individuals are children of phenotypically normal, heterozygous carriers. Heterozygotes may transmit the recessive allele to their offspring and are therefore carriers. Cystic fibrosis: European descent, one out of 25 (4%) is a carrier of the cystic fibrosis allele. Sickle Cell: most common in African descent. Caused by a substitution of a single amino acid in the hemoglobin protein of red blood cells. Oxygen content is affected and the red blood cells become deformed/sickled. Mating of Close relatives: o Consanguineous mating: if related, the probability of passing on recessive traits increases greatly.

Dominant Inherited Disorders: Achondroplasia: form of dwarfism with a prevalence of one among 25,000 people. Heterozygotes individuals have the dwarf phenotype. Lethal dominant alleles are eliminated from the population, if affected people die before reproducing. Can escape elimination if its causes death only at a relatively advanced age. o Huntingtons disease- a degenerative disease of the nervous system caused by a lethal dominant allele that has no obvious phenotypic effect until the individual is about 35-45 years old. It is irreversible and inevitably fatal.

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! Multifactorial Disorders: many human diseases such as most form of cancer and hear disease have both genetic and environmental components. These do not follow Mendelian inheritance patterns. Genetic Testing and Counseling: using family histories, genetic counselors help couples determine the odds that their children will have genetic disorders. Once a child is conceived, amniocentesis and chorionic villus sampling can help determine whether a suspected genetic disorder is present. o Amniocentesis: (within 14th-16th week of pregnancy) determines whether the fetus has Tay-Sachs disease. Inserts a needle into the uterus and extracts amniotic fluid; some genetic disorder can be detected from the presence of certain chemicals in the amniotic fluid. (can cause complications such as internal bleeding, maybe even death) o Chorionic Villus sampling (CVS): inserts a narrow tube into the cervix into the uterus and suctions out a tiny sample of tissue form the placenta(organ that transmits nutrients and fetal wastes between moth and fetus). ! Advantages: rapid analysis. Performed early, as much as the 8th-10th week of pregnancy. o Imaging techniques allow a physician to examine a fetus directly for major anatomical abnormalities. ! Ultrasound technique: sound waves are used to produce an image of the fetus by a noninvasive procedure. ! Fetoscopy: a needle thin tube containing a viewing scope and fiber optics is inserted into uterus. (Can cause complications such as internal bleeding, maybe even death) ! ! !

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Molecular Genetics RNA and DNA structure and function


DNA is the genetic material The two chemical components of chromosomesDNA and proteinbecame the candidates for the genetic material. Frederick Griffith in 1928 o studied two kinds of bacteria: a pathogenic(disease causing) one and a nonpathogenic(harmless) strain o Transformation: a change in genotype and phenotype due to the assimilation of external DNA by a cell. Avery, McCarty, MacLeod in 1944. o Announced that the transforming agent was DNA. ! Only DNA worked in transforming harmless bacteria into pathogenic bacteria. Hershey and Chase in 1952 o Showed that DNA is the genetic material of a bacteriophage known as T2.

Building a structural model of DNA: Scientific Inquiry Franklin & Wilkins produced a picture of the DNA molecule using X-ray crystallography. This allowed Watson to deduce that DNA was helical and to determine the width of the helix and the spacing of the nitrogenous bases. o Pairing a purine with a pyrimidine resulted in a uniform width o Adenine paired only with thymine and guanine paired only with cytosine. Many proteins work together in DNA replication and repair Watson and Crick first to reason: since the two strands of DNA are complementary each strand acts as a template for building a new strand in replication. Semiconservative Replication: each daughter molecule will have one old strand and one newly made strand. Meselson and Stahl- labeled nucleotides of DNA with a heavy isotope of nitrogen. o DNA replication occurs in presence of nucleotides labeled with a light isotope of N ! The first replication produced a band of hybrid DNA ! A second replication produced both light and hybrid DNA. Origins of Replication: the replication of a DNA molecule begins at these special sites. The two DNA strands separate, opening up a replication bubble. At the end of the bubble "#$%$&'!()*+,!-./#.0!

! is a replication fork; hundreds of origins of replication on a eukaryotic chromosome. Replication proceeds in both directions from each origin. Elongating a New DNA Strand: is catalyzed by enzymes called DNA polymerases. Each nucleotide that is added to a growing DNA strand is a nucleoside triphosphate. Antiparallel Elongation: DNA double helix is antiparallel. DNA polymerases add nucleotides only to the 3 end of a growing strand. Leading strand: DNA polymerases synthesizes the new strand continuously. Lagging strand: the DNA strand made by this mechanism. DNA polymerase must work away from the replication fork. o Synthesized as Okazaki fragments, which are joined together by DNA ligase. Priming DNA synthesis DNA polymerases cannot initiate synthesis of a new strand. The initial nucleotide strand is a short RNA or DNA primer. Primer may consist of either DNA or RNA and in initiating the replication of cellular DNA. An enzyme called primase can start an RNA chain from scratch. o One primer from leading strand, but each okazaki fragment must be primed separately on the lagging strand. Proteins that assist DNA Replication Helicase: an enzyme that untwists the double helix at the replication forks, separating the two parental strands and making them available as template strands. o Topoisomerase helps relieve this strain: corrects over winding ahead of the replication forks by breaking, swiveling and rejoining DNA strands. Single-strand binding protein: binds to and stabilizes single stranded DNA. Primase: synthesizes as RNA primer at the start of the leading strand and the Okazaki fragments. DNA pol III- synthesized the leading strand and Okazaki fragments DNA pol I- removes primer from the 5 ends of the leading strand and Okazaki fragments, replacing primer with DNA. DNA ligase: joins the 3 end of the DNA that replaces the primer to the rest of the strand.

Proofreading and Repairing DNA: "#$%$&'!()*+,!-./#.0!

! DNA polymerases proofread newly made DNA mismatch repair of DNA, repair enzymes correct errors in base errors. In nucleotide excision repair, enzymes cut out and replace damaged stretches of DNA. Replicating the ends of DNA molecules The unusual replication machinery does not complete 5 ends Repeated rounds of replication produce shorter DNA molecules. o Ends of eukaryotic chromosomal DNA molecules: nucleotide sequences called telomeres o Telomeres postpone the erosion of genes near the ends of DNA molecules. Telomerase: Essential genes would be missing from the gamete if germ cells shortened every generation. An enzyme called telomerase catalyzes the lengthening of telomeres in germ cells. Molecular Components of Transcription: RNA synthesis is catalyzed by RNA polymerase. It follows the same base-pairing rules as DNA replication except uracil is substituted for thymine. Synthesis of an RNA Transcript: Initiation: promoter signal the initiation of RNA synthesis Elongation: transcription factors help RNA polymerase recognize promoter sequences. Termination: mechanisms for termination differ in prokaryotes and eukaryotes. Eukaryotic cells modify RNA after transcription Alteration of mRNA ends: Eukaryotic mRNA molecules are processed before leaving the nucleus by modification of their ends and by RNA splicing. The 5 end receives a modified nucleotide cap The 3 end receives a poly-A tail. Split genes and RNA splicing Most eukaryotic genes have introns interspersed among the coding regions(exons). In RNA splicing, introns are removed and exons joined. RNA splicing is carried out by spliceosomes, but in some cases, RNA alone catalyzes splicing. Catalytic RNA molecules are called ribozymes. The presence of introns allows for alternative RNA splicing. Translation is the RNA-directed synthesis of a polypeptide Molecular Components of Translation: A cell translates an mRNA message into protein with the help of tRNA. After binding specific amino acids, tRNA molecules line up by means of their anticodons at complementary codons on mRNA. "#$%$&'!()*+,!-./#.0!

! Ribosomes help facilitate this coupling with binding sites for mTNA and tRNA.

Building a polypeptide: Ribosomes coordinate the three stages of translation: initiation, elongation and termination. The formation of peptide bonds between amino acids is catalyzed by rRNA. A number of ribosomes can translate a single mRNA molecule simultaneously, forming a polyribosome. Completing and targeting the functional protein After translation, proteins may be modified in ways that affect their 3d shape. Free ribosomes in the cytosol initiate the synthesis of all proteins RNA plays multiple roles in the cell: RNA can hydrogen bond to other nucleic acid molecules. It can assume a specific 3D shape. It has functional groups that allow it to act as a catalyst, a ribozyme. Comparing gene expression in prokaryotes and eukaryotes reveals key differences Because Prokaryotic cells lack a nuclear envelope, translation can begin while transcription is still in progress. In a eukaryotic cell, the nuclear envelope separates transcription, and extensive RNA processing occurs in the nucleus Point mutations can affect protein structure and function Types of Point mutation: A point mutation is a change in one DNA base pair, which may lead to production of a nonfunctional protein or no protein at all. Base pair substitutions can cause missense or nonsense mutations. Base pair insertions or deletions may produce frame shift mutations. Mutagens: spontaneous mutations can occur during DNA replication, recombination or repair. Chemical and physical mutagens can also alter genes.

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Gene Regulation
Embryonic Development involves cell division, cell differentiation and morphogenesis In addition to mitosis: embryonic cells undergo differentiation, become specialized in structure and function. Morphogenesis encompasses the processes that give shape to the organism and its various parts Several model organisms are commonly used to study different aspects of the genetic base of development. Different cell types result from differential gene expression in cells with the same DNA. Evidence for Genomic Equivalence: cells differ in structure and function not because they contain different genes but because they express different portions of a common genome o They have genomic equivalence. Differentiated cells from mature plants are often o Totipotent: capable of generating a complete new plant. Can develop in to ANY time of cell o Pluripotent: stem cells from animal embryos or adult tissues can reproduce and differentiate in vitro as well as in vivo, offering the potential for medicine. Transcriptional Regulation of Gene Expression During Development: Differentiation is heralded by the appearance of tissue-specific proteins. These proteins enable differentiated cells to carry out their specialized roles. Cytoplasmic Determinants and Cell-Cell signals in cell differentiation: Cytoplasmic determinants in the cytoplasm of the unfertilized egg regulate the expression of genes in the zygote that affect the developmental fate of embryonic cells. In the process of induction, signal molecules from embryonic cells cause transcriptional changes in nearby target cells. Pattern formation in animals and plants results from similar genetic and cellular mechanisms: pattern formation, the development of a spatial organization of tissues and organs, occurs continually in plants but is most limited to embryos and juveniles in animals. Positional information, the molecular cues that control pattern formation, tell a cell its location relative to the bodys axes and to other cells. Drosophila Development: A cascade of gene activations: After fertilization, positional information on an increasingly fine scale specifies the segments in Drosophila and triggers the formation of each segments characteristic structure. "#$%$&'!()*+,!-./#.0!

! Gradients of morphogens encoded by maternal effect genes such as bicoid, produce regional differences in the sequential expression of three sets of segmentation genes. Master, homeotic genes, specifies the type of appendages and other structures that form on each segment. o Transcription factors encoded by homeotic genes are regulatory proteins that control the expression of genes responsible for specific anatomical structures. Pattern formation"maternal effect"bicoid"homeotic genes C. elegans: the role of cell signaling: cell signaling and induction are critical in determining worm cell fates, including apoptosis An inducing signal produced by one cell in the embryo can initiate a chain of inductions that results in the formation of a particular organ. Plant development: Cell signaling and Transcriptional Regulation: Induction by cell-cell signaling helps determine the numbers of floral organs that develop from a floral meristem. Organ identity genes determine the type of structure (stamen, carpal, sepal or petal) that grows from each whorl of floral meristem. o act as master regulatory genes, each controlling the activity of other genes that more directly bring about an organs structure and function.

Viral and bacterial structure and replication


A virus has a genome but can reproduce only within a host cell Researchers discovered viruses in the late 1800s by studying a plant disease, tobacco mosaic disease. A virus is a small nucleic acid genome enclosed in a protein capsid and sometimes a membranous envelope containing viral proteins that help viruses enter cells. The genome may be single or double stranded DNA or RNA. Reproductive Cycles of Phages: Lytic cycle: entry of the viral genome into a bacterium programs o destruction of host DNA, o production of new phages o digestion of the hosts cell walls. o Lysogenic cycle: the genome of a temperate phage inserts into a bacterial chromosome as a prophage which is passed on to host daughter cells until it is induced to leave the chromosome and initiate the lytic cycle.

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! Many animal viruses have an envelope. Retroviruses use the enzyme reverse transcriptase to copy their RNA genome into DNA, which can be integrated into the host genome as a provirus. Evolution of Viruses: since viruses can reproduce only within cells, they probably evolved after the first cells appeared, perhaps as packaged fragments of cellular nucleic acid. Similarties: in both life cycles the virus/phage attaches to the bacterium and injects its DNA. Differences: Lysogeny, the Phage DNA circulates and integrates with the host DNA. In contrast, in the lytic cycle, the viral DNA uses cellular machinery to reproduce itself; the protein coats are produced from viral DNA genes and then the viruses can reassemble.

Viruses, viroids and prions are formidable pathogens in animals and plants. Viral Diseases in Animals: symptoms may be caused by direct viral harm to cells or by the bodys immune response. Vaccines stimulate the immune system to defend the host against specific viruses Emerging Viruses: outbreaks of new viral diseases in humans are usually caused by existing viruses that expand their host territory. Viral Diseases in Plants: viruses enter plant cells through damaged cell walls or are inherited from a parent Viroids and Prions: The Simplest Infectious Agents: o Viroids: plant pathogens that have single stranded RNA and no protein coat. Viroid RNA does not code for any protein. Naked RNA molecules that infect plants and disrupt plant growth. o Prions: infectious particles composed primarily of proteins (beta form). They are slow acting, virtually indestructible infectious proteins that cause brain diseases in mammals. Rapid reproduction, mutation and genetic recombination contribute to the genetic diversity of bacteria The bacterial genome and its replication: the bacterial chromosome is usually a circular DNA molecule with few associated proteins. Plasmids are smaller circular DNA molecules that can replicate independently of the chromosome. Mutation and Genetic Recombination as Sources of Genetic Variation Because bacteria can proliferate rapidly, new mutations can quickly increase a populations genetic variation. Further diversity can arise by recombination of the DNA from two different bacterial cells.

Gene Transfer and Genetic Recombination in Bacteria. "#$%$&'!()*+,!-./#.0!

! Transformation: when a host organism takes in free-floating DNA. Transduction: when bacteriophages attach to the membrane and inject viral DNA. The viral DNA can then replicate. Transduction includes both the lytic and lysogenic cycles. Conjugation: when a sex pilus protrudes from a bacterium it can attach to another bacterium in which DNA can then be transferred.

Transposition of Genetic Elements: DNA segments that can insert at multiple sites in a cells DNA contribute to genetic shuffling in bacteria. Insertion sequences, the simplest bacterial transposable elements, consist of inverted repeats of DNA flanking a gene for transposes. Bacterial transposons have additional genes, such as those for antibiotic resistance. Transporons are DNA segments that can move from one location to another via plasmids. It then moves from the plasmid onto the host cell genome. It is capable of replicating and moving to other segments of the host cells genome and also refusing with plasmids. Individual bacteria respond to environmental change by regulating their gene expression. Operon: unit of genomic material containing genes under the control of a promoter; cells control metabolism by regulating enzyme activity or the expression of genes coding for enzymes. In bacteria, genes are often clustered into operons, with one promoter serving several adjacent genes. An operon site on the DNA switches the operon on or off. Repressible and Inducible Operons: Negative Gene Regulation: In Inducible systems (ex. Lac operon) a specific substance interacts with the repressor molecule; this interaction releases the repressor molecule and it now incapable of preventing synthesis. Lac operon is an inducible system(meaning it is always off unless turned on). When Lactose, a specific inducer molecule appears in cell and turns on the lac operon. A repressor molecule prevents gene expression from binding from upstreming controlling system. Lactose attaches to the repressor molecule, and releases the molecule from the controlling region. Then RNA polymerase can then begin transcription of operon. In Repressible systems (ex Trp operon), a specific substance interacts with the repressor molecule and this then blocks or stops synthesis. Trp operon is a repressible system. The operon is automatically turned on unless a repressor becomes active and turns it off. When the operon is turned on, RNA polymerase can attach to the promoter region and begin synthesis of n mRNA transcript. Positive Gene Regulation: some operons are also subject to positive control via a stimulatory activator protein such as catabolite activator protein(CAP), which promotes "#$%$&'!()*+,!-./#.0!

! transcription when bound to a site within the promoter.! !

Nucleic acid technology and applications


DNA cloning permits production of multiple copies of a specific gene or other DNA segment DNA cloning can be used to manipulate and analyze DNA and to produce useful new products and organisms. Bacterial restriction enzymes cut DNA molecules within short, specific nucleotide sequences to yield a set of double-stranded DNA fragments with single stranded sticky ends. The sticky ends on fragments from one DNA source can case-pair with complementary sticky ends on fragments from other DNA molecules; sealing of the base-paired fragments with DNA ligase produces recombinant DNA molecules Cloning a Eukaryotic Gene in a bacterial plasmid: a recombinant plasmid is made by inserting restriction fragments from DNA containing a gene of interest into a plasmid vector that has been cut open by the same enzyme. Gene cloning results when the recombinant plasmids are introduced into a host bacterial cell and the foreign genes are replicated along with the bacterial chromosomes as the host cell reproduces. A clone of cells carrying the gene of interest can be identified with radioactively labeled nucleic acid probe that has a sequence complementary to the gene. Storing Cloned Genes in DNA libraries. A genomic library is the collection of recombinant vector clones produced by cloning DNA fragments derived from an entire genome. A cDNA(complementary DNA) library is made by cloning DNA made in vitro by reverse transcriptase of all the mRNA produced by a particular kind of cell. Amplifying DNA in vitro: The Polymerase Chain Reaction (PCR) PCR can produce many copies of a specific target segment of DNA, using primers that bracket the desired sequence and a heat-resistant DNA polymerase. Restriction fragments analysis detects DNA differences that affect restriction sites Gel Electrophoresis and Southern Blotting: DNA restriction fragments of different lengths can be separated by gel electrophoresis. Specific fragments can be identified by Southern blotting, using labeled probes that hybridize to the DNA immobilized on a blot of the gel. How do we visualize RFLPs? Cut DNA samples with restriction enzymes. This leads to DNA fragments of different length; these are separated by gel "#$%$&'!()*+,!-./#.0!

! electrophoresis. RFLPs also allow s to identify groups of people at risk for genetic disorders. Entire genomes can be mapped at the DNA level Genetic(linkage) mapping: the order of genes and other inherited markers in the genome and the relative distances between them can be determined by recombinant frequencies. Physical mapping: ordering DNA fragments. a physical map is constructed by cutting a DNA molecule into many short fragments and arranging them in order by identifying overlaps. A physical map gives an actual distance in case pairs between markers. DNA sequencing: relatively short DNA fragments can be sequenced by the dideoxy chain termination methods, which can be performed in automated sequencing machines. Genome sequences provide clues to important biological questions Identifying protein-coding genes in DNA sequences: computer analysis of genome sequences helped researches identify sequences that are likely to encode proteins. Comparison of the sequences of new genes with those of known genes in other species may help identify new genes. Determining Gene Function: for a gene of unknown function, experimental inactivation of the gene and observation of the resulting phenotypic effects can provide clues to its function. DNA microarray assays allow researchers to compare patterns of gene expression in difficult tissues, at different times, or under different conditions. Comparing Genomes of Different Species: comparative studies of genomes from related and widely divergent species are providing valuable information in many fields of biology. Future directions in genomics: genomics is the systematic study of entire genomes; proteomics is the systematic study of all the proteins encoded by a genome. Single nucleotide polymorphisms provide useful markers for studying human genetic variation. The practical applications of DNA technology affect our lives in many ways Medical applications: DNA technology is increasingly being used in the diagnosis of genetic and other diseases and offers potential for better treatment of certain genetic disorders or even permanent cures. Pharmaceutical products: large-scale production of human hormones and other proteins with therapeutic uses, including safer vaccines, are possible with DNA technology. Forensic Evidence: DNA fingerprints obtained by analysis of tissue or body fluids found at crime scenes can provide definitive evidence that a suspect is guilty or not. "#$%$&'!()*+,!-./#.0!

Environmental Cleanup: genetic engineering can be used to modify the metabolism of microorganisms so that they can be used to extract minerals from the environment or degrade various types of potentially toxic waste materials Agricultural Applications: the aim of developing transgenic plants and animals is to improve agricultural productivity and food quality. ! ! !

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Evolutionary Biology Early evolution of life


Conditions on early Earth made the origin of life possible 1) abiotic(nonliving) synthesis of small organic molecules 2) joining of these small molecules(monomers) into polymers including proteins and nuclei acids 3) packaging of these molecules into protobionts" droplets with membranes that maintained an internal chemistry different from that of their surroundings 4) origin of self-replicating molecules that eventually made inheritance possible. Synthesis of Organic compounds on Early Earth: Earth formed about 2.6 billion years ago. Laboratory experiments stimulating a reducing atmosphere have produced organic molecules from inorganic precursors. Amino acids have also been found on meteorites Abiotic Synthesis of Polymers o Amino acids polymerize when added to hot sand, clay or rock o Polymerize: production of amino acid polymers. Protobionts: organic compounds can spontaneously assemble in the laboratory into protobionts" lipid bounded droplets that have some of the properties of cells RNA World + Dawn of natural selection first genetic material = short pieces of RNA that served as templates for aligning amino acids in polypeptide synthesis(translation) and aligning nucleotides in a primitive form of self replication. Early protobionts with self replicating catalytic RNA would be more effective at using resources and increased by natural selection The fossil record chronicles life on earth: How rocks and fossils are dated: sedimentary strata reveal the relative ages of fossils. The absolute age of fossils can also be determined through radiometric dating. The trapping of dead organisms in sediments freezes time. Radiometric dating" based on decay of radioactive isotopes. Each isotope has a fixed rate of decay Strata at one location may be correlated with strata at another location by the presence of similar fossils known as index fossils(ex. Shells of marine organisms) The Geologic record: earths history is divided into geologic eons, eras, and periods, many of which mark major changes in the composition of fossil species Achaean and the Proterozoiclasted 4 billion years. Referred to as Precambrian o Achaean: origin of earth" oldest rocks and fossils of cells" concentration of atmospheric oxygen "#$%$&'!()*+,!-./#.0!

! o Proterozoic: oldest fossils of eukaryotes " diverse algae and soft bodied invertebrate animals Phanerozoic eon: "lasted half billion year & encompasses most of the time multicellular eukaryotic life has existed on earth. Three Eras: o Paleozoic: o sudden increase in diversity of animal phyla (Cambrian) o marine algae abundant, colonization of land by plants and arthropods (Ordovician) o diversification of early vascular plants(Silutian), o diversification of body, first tetrapod and insects (Devonian), o extensive forests of vascular plants, seed plants, origin of reptiles, amphibians dominant(Carboniferous), o Radiation of reptiles, origin of present day insects, extinction of many mane and terrestrial organisms(Permian) o Mesozoic: age of reptiles "abundance of reptiles fossils including dinosaurs o Cone bearing plants, dominant landscape, radiation of dinosaurs, origin of mammal like reptiles(Triassic) o Gymnosperms, dinosaurs abundant and diverse(Jurassic) o Flowering plants, dinosaurs become extinct (Cretaceous) o Cenozoic: o mammals, birds, pollinating insects, angiosperm dominance, modern mammalian orders, and primate groups (including apes) (palogene) o mammals, angiosperms, apelike ancestors of humans" origin of genus Homo, ice ages humans appear(Neogene) Mass extinction: evolutionary history has been punctuated by several mass extinctions followed by grand episodes of adaptive radiation. Extinctions may have been caused by volcanic activity or impacts from meteorites or comets.

Evidence for evolution


Prokaryotes evolved, they exploited and changed young earth First prokaryotes" prokaryotes were Earths sole inhabitant from 3.5 2 bill years ago Electron transport systems" first electron transport chains may have saved ATP by coupling the oxidation of organic acids to the transport of hydrogen ions out of the cell Photosynthesis and the Oxygen Revolution: Oxygenic photosynthesis evolved 3.5 billion years ago in cyanobacteria Eukaryotic cells arose from symbioses and genetic exchanges between prokaryotes Oldest fossil: stromatolites, composed of many layers of bacteria and sediment. First eukaryotes were autotrophs and heterotrophs

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! Endosymbiotic Origin of mitochondria and plasmids: Eukaryotes have a cytoskeleton and can change shape, enabling them to surround and engulf other cells. Eukaryotes may have evolved as predates of other cells. Mitochondria and plasmids likely evolved from prokaryotes that were ingested by and lived symbiotically inside large cells Eukaryotic Cells as Genetic Chimeras: Additional endosymbiosis and horizontal gene transfers may have contributed to the complex structures of eukaryotic cells. Mitochondria derived from one type of bacteria and its plasmids from another. Genome is a product of genetic annealing" horizontal gene transfer between bacteria and Achaean lineages. Multicellularity evolved several times in eukaryotes First multicellular organism was colonies containing specialized cells. Snowball Earth hypothesis: most life would have been confined to area near deep-sea vents and hot springs or to regions of the ocean where ice had melted allowing sunlight to penetrate. Cambrian Explosion: Oldest fossils of most animal phyla date from the Cambrian period Even though molecular evidence dates that they originated much earlier. Colonization of Land by plants, fungi and animals Ex. Plants, which evolved from algae, have a waterproof coating of wax, minimizing water loss Roots of most plants are associated with fungi that aid in the absorption of water and minerals Continental Drift: rearranging landmasses, continental drift has significantly affected evolution. Formation and subsequent breakup of the supercontinent Pangaea explain many biogeographic puzzles New information has revised our understanding of the tree of life Previous taxonomic systems: early classification systems had two kingdoms: plant & animal Later taxonomic system has 5 kingdoms: Monera, Protista, Plantae, Fungi and Animalia ! !

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