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VCU BIOL 152 - Molecular Basis of Inheritance

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BIOL 152 1st Edition Lecture 5 Outline of Last Lecture - Evolution of Population Outline of Current Lecture Nucleic Acids and the Molecular Basis of InheritancePolypeptide structure- Genes consist of DNA, a polymer known as nucleic acids - Two types: DNA and RNA- DNA directs RNA synthesis, RNA directs polypeptide synthesisNucleic Acids - store and transmit hereditary informationGenes - products that are inherited and passed down- Are the units of inheritance- Program the amino acid sequence of polypeptides- Are made of nucleic acids- DNA not directly involved in cells functions Nucleic acids exist as polymers called polynucleotides joinedby phosphodiester bonds, which are phosphate backbonewith nitrogenous base appendagesNucleoside versus NucleotideNucleoside consists of a base and sugar Nucleotide consists of base, sugar, and phosphate Nitrogenous bases are either:- Pyrimidines o cytosineo thymine (DNA) o uracil (RNA) - Purines o adenineThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.o guanineDNA and RNA differ in the presence of an oxygen or hydroxyl group Directionality- 3’ end- 5’ end- The sequence of bases along a nucleotide polymer is unique for each gene- Genes are hundreds or thousands of nucleotides long - The linear order of bases in a gene specifies the amino acid sequence of a protein DNA structure- RNA is single-stranded- DNA is double- stranded – two polynucleotides spiral around an imaginary axis forming a double helix- Sugar phosphate backbone on the outside and nitrogenous bases paired on the interior - Nitrogenous bases form complementary hydrogen bonds - The structure is also antiparallel- Consists of covalent bonds in nucleic acid polymer, which are known and understoodDNA and Proteins as tape measures of evolution- Genes and their products (proteins) document hereditary background - Siblings have more similarities in DNA than unrelated individuals of same species- Extending this idea to between species: mostly related species share DNA similarities- Hemoglobin as example (146 amino acids in one polypeptide)o Humans and gorillas differ in __1o Humans and gibbons duffer in __2o Humans and rhesus monkeys differ in __8o Humans and mice differ in __27o Humans and frogs differ in __67The Molecular Basis of InheritanceGenes are located on chromosomesTwo chemical components of chromosomes (DNA and Protein) became candidates for genetic materialProteins seemed more likely because they had great heterogeneity and specificity of function, this is FALSELittle was known about nucleic acid and they seemed far too uniform to account for the multitude of specific inherited traits - Viral infections of Escherichia coli- 1952: A. Hershey and M. Chase showed that DNA is the genetic material of a bacteriophage known as T2 (composed entirely of DNA and protein) - Experiment: DNA not protein was the hereditary materialFranklin’s X-ray crystallography- Franklin concluded that sugar-phosphate backbone was outside and bases inside- Determined image and determined shape of DNAWatson and Crick- Deduced that DNA was a double helix- As well as complimentary base pairing - Chargaff’s rulesDNA Replication- Relationship exists between structure & function - Complimentary base pairing suggests a specific copying mechanism- Each strand acts as a template for building a new strand- Watson and Crick hypothesized that the parent molecule unwinds, and the two new daughter strands are built based on base-pairing rulesThree hypotheses for how replication occurred1. Conservative - Parent strands unwind and parents strands come together and daughter strands are formed2. Semiconservative - Parent strand unwind and each function as a template for synthesis of a new complementary strand. 3. Dispersive - mixture of old and new strandsDNA replication: closer look- Replication is semiconservative- Very fast considering the huge amount of information- 6 billion pairs within the hour- Many enzymes and proteins participate- Small differences in prokaryotic and eukaryotic cells In prokaryotic cells - DNA is circular- A single origin of replication- Proteins that initiate replication recognize this sequence and attach to the DNA, separate the two strands and open up a replication bubble- Replication is bidirectional and proceeds until the entire molecule has been replicated In eukaryotic cells - there are hundreds or thousands of replication origins - Elongation of new DNA- Occurs at a replication fork - Catalyzed by enzymes called DNA polymerases- Nucleotides added to 3 prime end of each new strand- Each nucleotide added is a nucleoside tri-phosphateHow does antiparallel structure affect replication?- Polymerases add nucleotides only to 3¢ end- 5 prime to 3 prime direction of replication- Along the leading, DNA polymerase III synthesizes a complementary strand continuously, moving toward the replication fork Priming DNA synthesis - Polymerases add nucleotides to the 3’ end of an existing chain that is already base paired to the template strand- The initial nucleotide chain is a primer- Primers - Initiate replication with help of primase - Act as the initial part of a new strand Antiparallel elongation- To elongate the lagging strand DNA polymerase III must work in the direction away from the replication fork- The lagging strand is synthesized as a series of segments called Okasaki fragments - 1000-2000 nucleotides long in bacteria and 100-200 in eukaryotes - Fragments are joined together by DNA Ligase Synthesizing the leading & lagging strands- Leading strand - primer + Pol III (+ Pol I + ligase)o Pol I replaces the RNA primer with DNA- Lagging - primer + Pol III + Pol I + ligase o Okazaki fragments createdo Need a primer, Pol III and Pol I for each fragmentEnzymesHelicase - Enzyme that untwists DNA parent strand at replication forksTopoisomerase - nicks DNA to relieve tension from unwinding Single-stranded binding protein - binds to and stabilizes single-stranded DNA before it is used as a template Proofreading and repairing DNA - Repair of errors in DNA is very important to the survival of organisms- 100 repair enzymes are known so far in humans- Errors are relatively rareo One in 10 billion nucleotides in final replicated DNA moleculeo However, one in 100,000 errors in initial base pairingo Corrected immediately by DNA polymerases Safeguarding the ends with telomeres - The


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