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Chapter 1 The Foundations of Biochemistry 1 4 Genetic Foundations Deoxyribonucleic acid DNA the genetic material o Sequence of nucleotides encodes instructions for forming all other cellular components The perpetuation of a biological species requires that its genetic information be o Maintained in a stable form o Expressed accurately o Reproduced with a minimum of errors Genetic Continuity Is Vested in Single DNA Molecules The Structure of DNA Allows for Its Replication and Repair with Near Perfect Fidelity Deoxyribonucleotides If one strand is damaged continuity of information is assured by the information in the other strand which can act as a template for repair four different monomeric subunits The Linear Sequence in DNA Encodes Proteins with Three Dimensional Structure A linear sequence of deoxyribonucleotides in DNA codes through RNA for the production of a protein with a corresponding linear sequence of amino acids The protein then folds into a particular three dimensional shape determined by its sequence and stabilized primarily by noncovalent interactions the precise three dimensional structure of a protein Native conformation o Crucial to function Chromosomes ribosomes and membranes are supramolecular complexes formed by noncovalent association of proteins with other macromolecules Accurate folding requires the right o pH o Ionic strength o Metal ion concentrations 1 5 Evolutionary Foundations Changes in the Hereditary Instructions Allow Evolution Mutation a change in the nucleotide sequence of DNA o Changes instructions for a cellular component o Can also be caused by incorrectly repaired damage o Can be harmful or lethal o Occasionally beneficial Wild type unmutate cells o Eliminated in natural selection Biomolecules First Arose by Chemical Evolution It is hypothesized that organic building blocks were produced through ultraviolet irradiation lightning or volcanic eruptions acting on the gases in the prebiotic Earth s atmosphere or on inorganic solutes in superheated thermal vents deep in the ocean RNA can act as a catalyst RNA or Related Precursors May Have Been the First Genes and Catalysts DNA and protein may have appeared simultaneously and RNA preceded both space Biological Evolution Began More Than Three and a Half Billion Years Ago The First Cell Probably Used Inorganic Fuels The earliest cells arose in a reducing anaerobic atmosphere and probably obtained energy from inorganic fuels An alternative source of organic compounds could have been extraterrestrial A significant evolutionary event was the development of pigments capable of capturing energy from light which could be used to reduce CO2 to form more complex organic compounds Cyanobacteria are the modern descendants of early photosynthetic oxygen producers Earliest cells were anaerobic o The transfer of electrons from organic molecules to O2 releases a lot of energy so organisms that could do this had an advantage Eukaryotic Cells Evolved from Simpler Precursors in Several Stages Three major changes must have occurred o As cells acquired more DNA the mechanisms required to fold it compactly into discrete complexes with specific proteins and to divide it equally between daughter cells at cell division became more elaborate Specialized proteins were required o As cells became larger a system of intracellular membranes o Endosymbiotic developed segregating processes associations enveloping of aerobic bacteria or photosynthetic bacteria by early eukaryotic cells that eventually became permanent Clustering was advantageous and led to cellular differentiation Molecular Anatomy Reveals Evolutionary Relationships Genome Homologs Paralogs the complete genetic endowment of an organism two genes that share readily detectable sequence similarities two homologous genes that occur in the same species o Usually have different functions Orthologs two homologous genes found in different species o Usually have the same function Annotated genome accompanying the sequence a description of the likely function of each gene product Functional Genomics Shows the Allocations of Genes to Specific Cellular Processes The more complex an organism the greater the proportion of its genome that encodes genes involved in the regulation of cellular processes Genomic Comparisons Have Increasing Importance in Human Biology and Medicine


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MSU BMB 462 - Chapter 1 – The Foundations of Biochemistry

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