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1 The Genetic Code of Genes and Genomes

1 The Genetic Code of Genes and Genomes

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1 The Genetic Code of Genes and Genomes

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  1. 1 The Genetic Code of Genes and Genomes

  2. DNA: Molecule of Heredity • Inherited traits are affected by genes that are transmitted from parents to offspring in reproduction • Genes are composed of the chemical deoxyribonucleic acid = DNA Fig. 1.6

  3. DNA: Molecule of Heredity • DNA was discovered by Friedrich Miescher in 1869 • In 1920s microscopic studies with special stains showed that DNA is present in chromosomes • In 1944 Avery, McLeod and McCarty provided the first evidence that DNA is the genetic material

  4. Avery, McLeod, McCarty Experiment • Avery, McLeod and McCarty identified the chemical substance responsible for changing rough, nonvirulent cells of Streptococcuspneumoniae (R) into smooth encapsulated infectious cells (S): • Transforming activity was destroyed by DNAse, not RNAse or protease • Conclusion: transforming factor that converts R cells to S cells is DNA

  5. Fig. 1.3

  6. Hershey-Chase Experiment • In 1952 Hershey and Chase showed that DNA, not protein, is responsible for phage activity in bacterial cells: • Radioactive phage DNA enters bacteria after attachment, but protein coat of virus remains outside • Phage DNA directs the reproduction of virus in infected bacterial cells

  7. DNA Structure: Double Helix • In 1953 Watson and Crick proposed the three dimensional structure of DNA • Molecular structure of DNA is a double-stranded helix comprised of a linear sequence of paired subunits = nucleotides • Each nucleotide contains any one of four bases = adenine, thymine, guanine and cytosine • Pairing between nucleotides of the double helix is complementary: adenine pairs with thymine guanine pairs with cytosine

  8. DNA Structure: Double Helix • DNA backbone forms right-handed helix • Each DNA strand has polarity = directionality • The paired strands are oriented in opposite directions = antiparallel Fig. 6.7

  9. DNA Replication • Watson-Crick model of DNA replication: • The strands of the original (parental) duplex separate • Each parental strand serves as a template for the production of a complementary daughter strand by means of A-T and G-C base pairing

  10. Genes and Proteins • The genetic information contained in the nucleotide sequence of DNA specifies a particular type of protein • Enzymes = proteins that are biological catalysts essential for metabolic activities in the cell • Metabolites = small molecules upon which enzymes act • In 1908 Archibald Garrod proposed that enzyme defects result in inborn errors of metabolism = hereditary diseases

  11. Genes and Proteins • Garrod studied alkaptonuria and identified abnormal excreted substance = homogentisic acid • Alkaptonuria results from a metabolic defect that blocks the conversion of a substrate molecule to a product molecule in a biochemical pathway due to absence of required enzyme = metabolic block • In case of alkaptonuria, a defective homogentisic acid 1,2 dioxygenase is unable to converts homogentisic acid into 4-maleylacetoacetic acid in the pathway for the breakdown of phenylalanine and thyrosine

  12. Genes and Proteins • Another defective enzyme in the same pathway, phenylalanine hydroxylase (PAH), leads to phenylalanine accumulation which causes the condition known as phenylketonuria (PKU) • Incidence of PKU, characterized by severe mental retardation, is about one in 8000 among Caucasian births. • A defective enzyme results from a mutant gene

  13. Central Dogma Central Dogma of molecular genetics: • DNA RNA Protein • DNA is the informational molecule which does not code for protein directly but rather acts through RNA intermediate • DNA codes for RNA = transcription • RNA codes for protein = translation

  14. Fig. 1.14

  15. Transcription • Transcription is the production of an RNA strand that is complementary in base sequence to a DNA template = messenger RNA (mRNA) • RNA contains the base uracil in place of thymine and the sugar ribose instead of deoxyribose • RNA is synthesized from template DNA following strand separation of the double helix Fig. 1.15

  16. Base pairing in DNA and RNA • Complementary base pairing specifies the linear sequence of bases in RNA • Adenine pairs with uracil; thymine pairs with adenine; guanine pairs with cytosine

  17. Translation • The sequence of bases in mRNA codes for the sequence of amino acids in a polypeptide • The mRNA is translated in nonoverlapping group of three bases = codons that specify the sequence of amino acids in proteins • Each codon specifies one amino acid • Transfer RNAs (tRNA) contain triplet base sequences = anticodons, which are complementary to codons in mRNA

  18. Fig. 1.16

  19. Translation • Translation occurs at the ribosomes which contain several types of ribosomal RNA (rRNA) • tRNAs participate in translation by carrying amino acids and positioning them on ribosomes • Translation results in the synthesis of a polypeptide chain composed of a linear sequence of amino acids whose order is specified by the sequence of codons in mRNA

  20. Mutations • Mutation refers to any heritable change in a gene • The change may be: substitution of one base pair in DNA for a different base pair; deletion or addition of base pairs • Any mutation that causes the insertion of an incorrect amino acid in a protein can impair its function

  21. Genes and Environment • One gene can affect more than one trait = pleiotropy • Any trait can be affected by more than one gene as well as environment • Most complex traits are affected by multiple genetic and environmental factors • Often several genes are involved in genetic disorders and the severity of a disease may depend upon genetic status and environmental factors

  22. Evolution • All creatures on Earth share many features of the genetic apparatus and many aspects of metabolism • Groups of related organisms descend from a common ancestor • Evolution occurs whenever a population of organisms with a common ancestry gradually changes in genetic composition over time

  23. Fig. 1.21

  24. Evolution • The totality of DNA in a single cell = genome • The complete set of proteins encoded in the genome = proteome • Genes or proteins that derive from a common ancestral sequence via gene duplication = paralogs • Genes that share a common ancestral gene via speciation = orthologs • The molecular unity of life is seen in comparisons among genomes and proteomes