notes 16

Molecular Biology Chapter 16 The first gene (human) Wilhelm Scribonius Described the condition of inky urine in 1584 Seen as a medical curiosity because Scribonius got distracted by other issues… In 1891, cause of inky urine was described Excess alkapton (homogentisic acid) in urine Disorder named alkaptonuria Achibald Garrod Present at birth Often affected siblings, but not parents Parents were often first cousins Garrod worked with William Bateson Garrod synthesized genetics with his observations Alkaptonuria caused by a single gene Recessive trait More likely to get homozygous recessive genotypes with inbreeding Homogentisic acid is chemically similar to amino acids phenylalanine and tyrosine Garrod hypothesized that HGA was the breakdown product of those amino acids Missing enzyme in homozygous recessive individuals= enzyme that breaks down HGA 1 gene= 1 enzyme hypothesis Inborn Errors of Metabolizm, 1908 Ignored until he 1940s 1 gene/ 1 enzyme George Beadle and Edward Tatum, Neurospora crassa Mutate N. crassa with high levels of radiation Created mutantsthat couldn’t grow without pyridoxine (B6) Formalized the 1 gene/ 1 enzyme hypothesis Adrian Srb and Norman Horowitz N. crassa can synthesize arginine They hypothesized that each intermediate in the pathway must have its own enzyme Generate many mutants that can’t survive without arginine How could you identify which enzyme is broken? Example 4 compounds in the pathway (critical for growth) W,X,Y,Z 3 knockout mutants Mut1, Mut2, Mut3 In what order are the compounds made? Answer: W, Z, X, Y Example 6 compounds in the pathway (critical for growth) A,B,C,D,E,F 5 knowckout mutants Mut1, Mut2, Mut3, Mut4, Mut5 Match the mutant with the enzyme/product. In what order are the compounds made? Answer: F, D, A, E, C, B Central dogma of moleculat biology What is the relationship between genes and proteins? Crick proposed that DNA sequences are a code Information not directly translated from the DNA directly Messenger RNA (mRNA) acts as an intermediary between DNA and proteins RNA polymerase can read information in DNA, transcribe it as RNA Experimental evidence: Place into tube: RNA polymerase Ribonucleotides: A, U, G, C DNA as a template (TTTTTTTTTTTT) RNA molecules with the equence AAAAAAAAAAAA are formed The flow of information in a cell is: DNA RNA protein DNA sequence defines the RNA sequence which defines the amino acid sequence in a protein CENTRAL DOGMA OF MOLECULAR BIOLOGY DNA mRNA is transcription Genetic information is copied into another nucleic acid mRNA protein is translation nucleic acid sequence is converted into an amino acid sequence Expectations to the dogma Not all RNA molecules act as messengers Ribosomal RNA (rRNA) helps make proteins, but doesn’t code for any Transfer RNA (tRNA) carries amino acids to the ribosome Genetic Code 4 nucleic acids need to code for 20 amino acids How long is a “word”? 4²= 16 words 4?= 64 words Minimum possible size for “words” “words” = codons Codon= set of 3 nucleotides Codons specify different amino acids 64 codons > 20 amino acids Code is degenerate Properties of the code Redundant 18 amino acids have more than 1 codon Unambiguous 1 codon= 1 amino acid Nearly universal It is conservative Mutation effects are minimized The code lets us predict amino acid sequences from DNA sequences The code lets us approximate DNA sequences from amino acid sequences Why only approximate? What would the mRNA sequence be if the bottom strand is the template mRNA is made in the 5’-3’ direction using the same complimentary base pairing rules. Mutation Permanent change in the DNA New genotype New phenotype? Point mutations Mistakes sometimes slip through Single base change May or may not affect an individual’s evolutionary fitness A mutation’s effect depends on where it happens Silent mutation No change to an amino acid, probably no effect Missense mutation Change to an amino acid, effect depends on the specific change Nonsense mutation Mutation to a stop codon, usually bad Frameshift mutation Changes the reading frame, usually bad Themanranfar The man ran far Themaanranfar The maa nra nfa r Point mutations are inevitable Repaid mechanisms are not perfect About 60 mutations/ person! 444,000,000,000 new mutations in the current global population Chromosome level mutations Polyploidy/aneuploidy Translocation A piece of the chromosome breaks out, joins a different chromosome Inversion A piece of the chromosome breaks out, flips, reinserts itself Karyotype # and appearance of chromosomes in a cell Chromosome banding Creates a banding pattern correlated to the DNA sequence G-banding Dark bands= AT rich, light bands= GC rich Map viewer