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Lecture PowerPoint to accompany Molecular Biology Fifth Edition Robert F. Weaver Chapter 1 A Brief History Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. A Brief History • What is molecular biology? – The attempt to understand biological phenomena in molecular terms – The study of gene structure and function at the molecular level • Molecular biology is a melding of aspects of genetics and biochemistry 1-2 1.1 Transmission Genetics • Transmission genetics deals with the transmission of traits from parental organisms to their offspring • The chemical composition of genes was not known until 1944 – Gene - genetic units – Phenotype - observable characteristics 1-3 Mendel’s Laws of Inheritance • A gene can exist in different forms called alleles • One allele can be dominant over the other, recessive, allele • The first filial generation (F1) contains offspring of the original parents • If each parent carries two copies of a gene, the parents are diploid for that gene 1-4 Mendel’s Laws of Inheritance • Homoozygotes have two copies of the same allele • Heterozygotes have one copy of each allele • Parents in 1st mating are homozygotes, having 2 copies of one allele • Sex cells, or gametes, are haploid, containing only 1 copy of each gene • Heterozygotes produce gametes having either allele • Homozygotes produce gametes having only one allele 1-5 Summary • Genes can exist in several different forms or alleles • One allele can be dominant over the other, so heterozygotes having two different alleles of one gene will generally exhibit the characteristic dictated by the dominant allele • The recessive allele is not lost; it can still exert its influence when paired with another recessive allele in a homozygote 1-6 The Chromosome Theory of Inheritance • Chromosomes are discrete physical entities that carry genes • Thomas Hunt Morgan used the fruit fly, Drosophila melanogaster, to study genetics • Autosomes occur in pairs in a given individual (not the X or the Y chromosome) • Sex chromosomes are identified as X and Y – Females have two X chromosomes – Males have one X and one Y chromosome 1-7 Location of Genes on a Chromosome • Every gene has its place, or locus, on a chromosome • Genotype is the combination of alleles found in an organism • Phenotype is the visible expression of the genotype – Wild-type phenotype is the most common or generally accepted standard – Mutant alleles are usually recessive 1-8 Genetic Recombination and Mapping • In early experiments genes on separate chromosomes behaved independently • Genes on the same chromosome behaved as if they were linked • This genetic linkage is not absolute • Offspring show new combinations of alleles not seen in the parents when recombination occurs 1-9 Recombination • During meiosis, gamete formation, crossing over can occur resulting in the exchange of genes between the two homologous chromosomes • The result of the crossing-over event produces a new combination of alleles • This process is called recombination 1-10 Genetic Mapping • Morgan proposed that the farther apart two genes are on a chromosome, the more likely they are to recombine • If two loci recombine with a frequency of 1%, they are said to be separated by a map distance of one centimorgan (named for Morgan) • This mapping observation applies both to prokaryotes and to eukaryotes 1-11 Physical Evidence for Recombination • Microscopic examination of the maize chromosome provided direct physical observation of recombination using easily identifiable features of one chromosome • Similar observations were made in Drosophila • Recombination was detected both physically and genetically in both animals and plants 1-12 Summary • The chromosome theory of inheritance holds that genes are arranged in linear fashion on chromosomes • Certain traits tend to be inherited together when the genes for those traits are on the same chromosome • Recombination between two homologous chromosomes during meiosis can scramble the parental alleles to yield nonparental combinations • The farther apart two genes are on a chromosome the more likely it is that recombination will occur 1-13 1.2 Molecular Genetics • The Discovery of DNA: The general structure of nucleic acids was discovered by the end of the 19th century – Long polymers or chains of nucleotides – Nucleotides are linked by sugars through phosphate groups • Composition of Genes: DNA? RNA? Protein? In 1944, Avery and his colleagues demonstrated that genes are composed of DNA 1-14 The Relationship between Genes and Proteins • Experiments have shown that a defective gene gives a defective or absent enzyme • This lead to the proposal that one gene is responsible for making one enzyme • Proposal not quite correct for 3 reasons: 1. One enzyme may be composed of several polypeptides, each gene codes for only one polypeptide 2. Many genes code for non-enzyme proteins 3. End products of some genes are not 1-15 polypeptides (i.e. tRNA, rRNA) Activities of Genes Genes perform three major roles • Replicated faithfully • Direct the production of RNAs and proteins • Accumulate mutations thereby allowing for evolution 1-16 Replication • Franklin and Wilkins produced x-ray diffraction data on DNA, Watson and Crick proposed that DNA is double helix – Two DNA strands wound around each other – Strands are complementary – if you know the sequence of one strand, you automatically know the sequence of the other strand • Semiconservative replication keeps one strand of the parental double helix conserved in each of the daughter double helices 1-17 Genes Direct the Production of Polypeptides • Gene expression is the process by which a gene product is made • Two steps are required – 1. Transcription: DNA is transcribed into RNA – 2. Translation: the mRNA is read or translated to assemble a protein – Codon: a sequence of 3 nucleic acid bases that code for one amino acid within the mRNA 1-18 Genes Accumulate Mutations Genes change in several ways • Change one base to another • Deletions of one base up to a large segment • Insertions of one base up to a large segment • The more drastic the change, the more likely it is that the gene or genes involved will be totally inactivated 1-19 Summary • All cellular genes are made of DNA arranged in a double helix • This structure explains how genes replicate, carry information and collect mutations • The sequence of nucleotides in a gene is a genetic code that carries the information for making an RNA • A change in the sequence of bases constitutes and mutation, which can change the sequence of amino acids in the genes polypeptide product 1-20 1.3 The Three Domains of Life Current research theories support the division of living organisms into three domains 1. Bacteria 2. Eukaryota 3. Archaea • Like bacteria as they are organisms without nuclei • More similar to eukaryotes in the context of their molecular biology 1-21 Archaea Archaea live in the most inhospitable regions of the earth • Thermophiles tolerate extremely high temperatures • Halophiles tolerate very high salt concentrations • Methanogens produce methane as a by-product of metabolism 1-22