2IntroductionHereditary factors consist of DNA and reside on chromosomes.The collective body of genetic information in an organism is called the genome.
3Overview of early discoveries on the nature of the gene
410.1 The Concept of a Gene as a Unit of Inheritance (1) Mendel’s work became the foundation for the science of genetics.He established the laws of inheritance based on his studies of pea plants.
5The Concept of a Gene as a Unit of Inheritance (2) Characteristics of organisms are governed by units of inheritance called genes.Each trait is controlled by two forms of a gene called alleles.Alleles could be identical or nonidentical.When alleles are nonidentical, the dominant allele masks the recessive allele.
6The Concept of a Gene as a Unit of Inheritance (3) 2. A reproductive cell (gamete) contains one gene for each trait.a) Somatic cells arise by the union of male andfemale gametes.b) Two alleles controlling each trait are inherited; onefrom each parent.3. The pairs of genes are separated (segregated) during gamete formation.4. Genes controlling different traits segregate independently of each (independent assortment).
710.2 Chromosomes: The Physical Carriers of Genes (1) The Discovery of ChromosomesChromosomes were first observed in dividing cells, using the light microscope.Chromosomes are divided equally between the two daughter cells during cell division.Chromosomes are doubled prior to cell division.
8Cellular process in the roundworm following fertilization
9Chromosomes: The Physical Carriers of Genes (2) Chromosomes as the Carriers of Genetic InformationChromosomes are present as pairs of homologous chromosomes.During meiosis, homologous chromosomes associate and form a bivalent; then separate into different cells.Chromosomal behavior correlates with Mendel’s laws of inheritance.
11Chromosomes: The Physical Carriers of Genes (3) The chromosome as a linkage groupGenes that are on the same chromosome do not assort independently.Genes on the same chromosome are part of the same linkage group.The traits analyzed by Mendel occur on different chromosomes.
12Chromosomes: The Physical Carriers of Genes (4) Genetic Analysis in DrosophilaMorgan was the first to use fruit flies in genetic research.Morgan only had available wild type flies but one he developed his first mutant, it became a primary tool for genetic research.Mutation was recognized as a mechanism for variation in populations.Studies with Drosophila confirmed that genes reside on chromosomes.
14Chromosomes: The Physical Carriers of Genes (5) Crossing Over and RecombinationLinkage between alleles on the same chromosome is incomplete.Maternal and paternal chromosomes can exchange pieces during crossing over or genetic recombination.
16Chromosomes: The Physical Carriers of Genes (6) Crossing over and recombinationPercentage of recombination between a pair of genes is constant.Percentage of recombination between different pairs of genes can be different.The positions of genes along the chromosome (loci) can be mapped.Frequency of recombination indicates distance, and increases as distance increases.
17Chromosomes: The Physical Carriers of Genes (7) Mutagenesis and Giant ChromosomesExposure to a sublethal dose of X-rays increases the rate of spontaneous mutations.Cells from the salivary gland of Drosophila have giant polytene chromosomes.Polytene chromosomes have been useful to observe specific bands correlated with individual genes.“Puffs” in polytene chromosomes allow visualization of gene expression.
1910.3 The Chemical Nature of the Gene (1) DNA is the genetic material in all organisms.The Structure of DNA:The nucleotide is the building block of DNA.It consists of a phosphate, a sugar, and either a pyrimidine or purine nitrogenous base.There are two different pyrimidines: thymine (T) and cytosine (C).There are two different purines: adenine (A) and guanine (G).
22The Chemical Nature of the Gene (2) Nucleotides have a polarized structure where the ends are called 5’ and 3’ .Nucleotides are linked into nucleic acids polymers:Sugar and phosphates are linked by 3’,5’-phosphodiester bonds.Nitrogenous bases project out like stacked shelves.
23The Chemical Nature of the Gene (3) Chargaff established rules after doing base composition analysis:Number of adenine = number of thymineNumber of cytosine = number of guanine[A] + [T] ≠ [G] + [C]
24The Chemical Nature of the Gene (4) The Watson-Crick ProposalThe DNA molecule is a double helix.DNA is composed of two chains of nucleotides.The two chains spiral around each other forming a pair of right-hand helices.The two chains are antiparallel, they run in opposite directions.The sugar-phosphate backbone is located on the outside of the molecule.The bases are inside the helix.
26The Chemical Nature of the Gene (5) The Watson-Crick Proposal (continued)The DNA is a double helixThe two DNA chains are held together by hydrogen bonds between each base.The double helix is 2 nm wide.Pyrimidines are always paired with purines.Only A-T and C-G pairs fit within double helix.Molecule has a major groove and a minor groove.The double helix makes a turn every 10 residues.The two chains are complementary to each other.
30The Chemical Nature of the Gene (7) DNA SupercoilingDNA that is more compact than its relaxed counterpart is called supercoiled.
31The Chemical Nature of the Gene (8) DNA Supercoiling (continued)Underwound DNA is negatively supercoiled, and overwound DNA is positively supercoiled.Negative supercoiling plays a role in allowing chromosomes to fit within the cell nucleus.
32The Chemical Nature of the Gene (9) DNA Supercoiling (continued)Enzymes called topoisomerases change the level of DNA supercoiling.Cells contain a variety of topoisomerases.Type I – change the supercoiled state by creating a transient break in one strand of the duplex.Type II – make a transient break in both strands of the DNA duplex.
3510.4 The Structure of the Genome (1) The genome of a cell is its unique content of genetic information.The Complexity of the GenomeOne important property of DNA is its ability to separate into two strands (denaturation).
36The Structure of the Genome (2) DNA RenaturationRenaturation or reanneling is when single-stranded DNA molecules are capable of reassociating.Reanneling has led to the development of nucleic acid hybridization in which complementary strands of nucleic acids form different sources can form hybrid molecules.
37The Structure of the Genome (3) The Complexity of Viral and Bacterial GenomesThe rate of renaturation of DNA from bacteria and viruses depends on the size of their genome.
38The Structure of the Genome (4) The Complexity of the Eukaryotic GenomeReanneling of eukaryotic genomes shows three classes of DNA:Highly repeatedModerately repeatedNonrepeated
39The Structure of the Genome (5) Highly Repeated DNA Sequences – represent about 1-10% of total DNA.Satellite DNAs – short sequences that tend to evolve very rapidly.Minisatellite DNAs – unstable and tend to be variable in the population; form the basis of DNA fingerprinting.Microsatellite DNAs – shortest sequences and typically found in small clusters; implicated in genetic disorders.
41Fluorescence in situ hybridization and localization of satellite DNA
42The Structure of the Genome (6) Moderately Repeated DNA SequencesRepeated DNA Sequences with Coding Functions – include genes that code for ribosomal RNA and histones.Repeated DNA Sequences that Lack Coding Functions – do not include any type of gene product; can be grouped into two classes: SINEs or LINEs.Nonrepeated DNA Sequences – code for the majority of proteins.
44The Human Perspective: Diseases That Result from Expansion of Trinucleotide Repeats (1) Mutations occur in genes containing a repeating unit of three nucleotides.The mutant alleles are highly unstable and the number of repeating units tends to increase as the gene passes from parent to offspring.Type I disease are all neurodegenerative disorders resulting form expansion of CAG trinucleotides.
45Trinucleotide repeat sequences and human disease
46The Human Perspective: Diseases That Result from Expansion of Trinucleotide Repeats (2) Huntington’s disease (HD) result from ≥ 36 glutamine repeats in the huntingtin gene.The molecular basis of HD remains unclear but it is presumed that expanded glutamine repeats are toxic to brain cell.Type II diseases arise from a variety of trinucleotide repeats, and are present in parts of the gene that do not code for amino acids (i.e. fragile X syndrome).
4710.5 The Stability of the Genome (1) Whole Genome Duplication (Polyploidization)Polyploidization (or whole genome duplication) occurs when offspring receive more than two sets of chromosomes from their parents.Could be the result of hybrids from closely related parents.Could result from duplicate chromosomes not separated in embryonic cells.
48A sample of agricultural crops that are polyploid
49The Stability of the Genome (2) Duplication and Modification of DNA SequencesGene duplication occurs within a portion of a single chromosome.Duplication may occur by unequal crossing over between misaligned homologous chromosomes.Duplication has played a major role in the evolution of multigene families.
51The Stability of the Genome (3) Evolution of Globin GenesThe globin gene family includes hemoglobin, myoglobin, and plant leghemoglobin.Ancestral forms have given rise to recent forms by duplication, gene fusion, and divergence.Some sequences, called pseudogenes, resemble globin genes but are nonfunctional.
53The Stability of the Genome (4) “Jumping Genes” and the Dynamic Nature of the GenomeGenetic elements are capable of moving within a chromosome (transposition).Those mobile elements are called transposable elements.
54The Stability of the Genome (5) TranspositionOnly certain sequences can acts as transposons, but these insert into target sites randomly.It requires the enzyme transposase to facilitate insertion of transposons into target site.Bacterial trasnposition occurs by replication of the transposable element, followed by insertion.
56The Stability of the Genome (6) Transposition (continued)Integration of the element creates a small duplication in target DNA, which serves as a “footprint” to identify sites occupied by transposable elements.Retrotransposons use an RNA intermediate which produces a complementary DNA via reverse transcriptase; viruses such as HIV use this mechanism to replicate their genome.
57Pathways in the movement of transposable elements
58The Stability of the Genome (7) The Role of Mobile Genetic Elements in EvolutionSome moderately repeated sequences in human DNA (Alu and L1) are transposable elements.Possible evolutionary roles:Rearrangement of the genomeRegulation of gene expressionProduction of new genes
5910.6 Sequencing Genomes: The Footprints of Biological Evolution (1) The genomes of hundreds of organisms have been sequenced.In 2004 the “finished” version of the human genome was reported.It contains about 20,000 genes.Alternate splicing of messenger RNA may account for several proteins from one gene.Post-translational modifications also account for different protein functions.
61Sequencing Genomes: The Footprints of Biological Evolution (2) Comparative Genomics: “If It’s Conserved, It Must Be Important”DNA that is similar among related organisms is considered to be important, even when the precise role is still unclear.Some important DNA in humans may have a recent origin
62Small segments of DNA are highly conserved between humans and related species
63Sequencing Genomes: The Footprints of Biological Evolution (3) The Genetic Basis of “Being Human”By focusing on conserved sequence, we can learn about traits we share with other species.The gene FOXP2 in human differs very little from that in chimps, and is called the “speech gene”.Another gene is HAR1, which also differ little between humans and chimps and its function is unknown.The gene AMY1 encodes the enzyme amylase and its frequency is remarkably different between humans and chimps.
64Duplication of the amylase gene during human evolution
65Sequencing Genomes: The Footprints of Biological Evolution (4) Genetic Variation within the Human Species PopulationThe genome varies among different individuals due to genetic polymorphisms.DNA Sequence VariationThe most common variability among humans is at the single nucleotide difference.These sites are called single nucleotide polymorphisms (SNPs).
66Sequencing Genomes: The Footprints of Biological Evolution (5) Structural VariationSegments of the genome can change, and these changes may involve large segments of the DNA (structural variants).Recent studies indicate that intermediate-sized variants are more common than previously thought.
68The Human Perspective: Application of Genomic Analysis to Medicine (1) Until recently, the gene responsible for a disease was identified through traditional genetic linkage studies.However, the low penetrance of most genes for common diseases cannot be identified through family linkage studies.Genome-wide association studies look for links between a disease and polymorphisms located in the genome.
69The Human Perspective: Application of Genomic Analysis to Medicine (2) SNPs may play an important role is susceptibility to disease or act as genetic markers for susceptibility.SNPs can be inherited in blocks called haplotypes.Haplotype maps (HapMaps) are based on common haplotypes.HapMaps may lead to associations between disease and haplotypes.
71Experimental Pathways: The Chemical Nature of the Gene (1) The nature of the gene was discovered through a series of unrelated studies.Miescher first identified “nuclein” in white blood cell extracts and in salmon sperm.Levene proposed the tetranucleotide theory, indicating that DNA was a boring repetition of four nucleotides and could not be the genetic material.
72Experimental Pathways: The Chemical Nature of the Gene (2) Griffith carried out experiments with pneumococcus bacteria with different abilities to cause disease.He observed transformation in bacteria caused by a transforming principle.
74Experimental Pathways: The Chemical Nature of the Gene (3) Further experiments by Avery, MacLeod, and McCarty led to the conclusion that DNA was the transforming principle.Experiments done by Hershey and Chase using a bacteriophage confirmed that DNA and not protein is the genetic material.