How Genes Work Lecture Notes PDF

How Genes Work Lecture Outline 1. Central Dogma a) Genotype and Phenotype b) Exceptions to the Central Dogma 2. The Genetic Code a) Five Properties of the Genetic Code 3. Mutations a) Point Mutations b) Chromosome-level Mutations Lecture Outline 1. Central Dogma a) Genotype and Phenotype b) Exceptio...

How Genes Work Lecture Outline 1. Central Dogma a) Genotype and Phenotype b) Exceptions to the Central Dogma 2. The Genetic Code a) Five Properties of the Genetic Code 3. Mutations a) Point Mutations b) Chromosome-level Mutations Lecture Outline 1. Central Dogma a) Genotype and Phenotype b) Exceptions to the Central Dogma 2. The Genetic Code a) Five Properties of the Genetic Code 3. Mutations a) Point Mutations b) Chromosome-level Mutations What is the Central Dogma? A. DNA à protein à RNA B. DNA à RNA à Protein C. Protein à DNA à RNA D. Protein à RNA à DNA E. RNA à DNA à Protein What is the Central Dogma? A. DNA à protein à RNA B. DNA à RNA à Protein C. Protein à DNA à RNA D. Protein à RNA à DNA E. RNA à DNA à Protein Central Dogma The central dogma of molecular biology summarizes the flow of information in cells. The DNA sequence codes for the RNA sequence. DNA → RNA → proteins Genes are stretches of DNA that code for proteins. The mRNA sequence codes for the amino acid sequence of a protein. Linking the Central Dogma to Cellular Processes DNA replication Transcription is the process of using a DNA template to make a complementary RNA. Translation is the process of using the information in mRNA to synthesize a protein. Lecture Outline 1. Central Dogma a) Genotype and Phenotype b) Exceptions to the Central Dogma 2. The Genetic Code a) Five Properties of the Genetic Code 3. Mutations a) Point Mutations b) Chromosome-level Mutations Linking the Central Dogma to Phenotype An organism’s genotype is determined by the sequence of bases in its DNA. o Alleles of the same gene differ in their DNA sequence. o Proteins produced by different alleles of the same gene frequently differ in their amino acid sequence. An organism’s phenotype is a product of the proteins it makes. Lecture Outline 1. Central Dogma a) Genotype and Phenotype b) Exceptions to the Central Dogma 2. The Genetic Code a) Five Properties of the Genetic Code 3. Mutations a) Point Mutations b) Chromosome-level Mutations Exceptions to the Central Dogma Many genes code for RNAs that do not function as mRNAs and are not translated into proteins. These RNAs perform important functions. Information flow is: DNA → RNA Sometimes information flows from RNA back to DNA. Some viruses contain reverse transcriptase which synthesizes DNA from an RNA template. Information flow is: RNA → DNA Central Dogma During transcription, one of the two DNA strands called the template strand provides a template for ordering the sequence of nucleotides in an RNA transcript. During translation, the mRNA base triplets, called codons, are read in the 5¢ to 3¢ direction. Each codon specifies the amino acid to be placed at the corresponding position along a polypeptide. Each codon specifies the addition of one of 20 amino acids. How does the cell know which amino acid should be added? Lecture Outline 1. Central Dogma a) Genotype and Phenotype b) Exceptions to the Central Dogma 2. The Genetic Code a) Five Properties of the Genetic Code 3. Mutations a) Point Mutations b) Chromosome-level Mutations Review How many amino acids are there? 20 How many nucleotides are there in DNA? 4 The Genetic Code The genetic code specifies how a sequence of nucleotides codes for a sequence of amino acids. A group of three bases that specifies a particular amino acid is called a codon. The flow of information from gene to protein is based on a triplet code. Triplet code: a series of non-overlapping, three-nucleotide words. Why does it have to be triplets? The Genetic Code All 64 codons were deciphered by the mid-1960s. The Genetic Code Of the 64 triplets, 61 code for amino acids. The Genetic Code 1 of these 61 triplets (AUG) also codes for the start of an amino acid sequence. AUG codes for methionine and signals where protein synthesis starts. The Genetic Code 3 triplets are “stop” signals to end translation. The Genetic Code The genetic code is redundant but not ambiguous. The genetic code is also conservative. The Genetic Code Codons must be read in the correct reading frame (i.e., correct groupings) in order for the specified polypeptide to be produced. Example: ‘The red dog ate the cat.’ ‘T her edd oga tet hec at.’ ‘The her ere red edd ddo dog oga gat ate tet eth the hec eca cat.’ What mechanism ensures that an mRNA is read in the correct reading frame? Evolution of the Genetic Code The genetic code is nearly universal, shared by the simplest bacteria to the most complex animals. Genes can be transcribed and translated after being transplanted from one species to another. Analyzing the Genetic Code The genetic code is: Redundant: Unambiguous: Non-overlapping: Nearly universal: Conservative: Translate this mRNA. 5’ A U G G G C C A G U A G 3’ Met Gly Gln ___ Identify a 3’ to 5’ sequence of nucleotides in the DNA template strand for an mRNA coding for the polypeptide sequence: Phe-Pro-Lys. A. 3’-AAAGGGUUU-5’ B. 3’-TTCCCCAAG-5’ C. 3’-TTTCCAAAA-5’ D. 3’-AAGGGCTTC-5’ E. 3’-UUUCCCAAA-5’ Identify a 3’ to 5’ sequence of nucleotides in the DNA template strand for an mRNA coding for the polypeptide sequence: Phe-Pro-Lys. A. 3’-AAAGGGUUU-5’ B. 3’-TTCCCCAAG-5’ C. 3’-TTTCCAAAA-5’ D. 3’-AAGGGCTTC-5’ E. 3’-UUUCCCAAA-5’ Lecture Outline 1. Central Dogma a) Genotype and Phenotype b) Exceptions to the Central Dogma 2. The Genetic Code a) Five Properties of the Genetic Code 3. Mutations a) Point Mutations b) Chromosome-level Mutations Mutations A mutation is any permanent change in an organism’s DNA. There are different types of mutations. o Point mutations result from one or a small number of base changes. o Chromosome-level mutations are larger in scale. Give an example of a chromosome-level mutation that we have seen previously in this course. Consequences of Mutations Mutations can have different impacts on fitness: o Beneficial mutations increase the fitness of an organism. o Neutral mutations do not affect an organism’s fitness. o Deleterious mutations decrease the fitness of the organism. Define fitness The ability of an individual to produce viable offspring relative to others of the same species. Most mutations are neutral or deleterious. Some mutations are not in coding regions but can still affect phenotype by affecting gene expression. Lecture Outline 1. Central Dogma a) Genotype and Phenotype b) Exceptions to the Central Dogma 2. The Genetic Code a) Five Properties of the Genetic Code 3. Mutations a) Point Mutations b) Chromosome-level Mutations Point Mutations Base-pair substitution mutations occur when a mistake during DNA synthesis or DNA repair results in a different base at a particular location on the gene. Do point mutations matter? It depends Base-Pair Substitution: Silent Mutation Silent mutations have no effect on the amino acid produced by a codon because of redundancy in the genetic code. Base-Pair Substitution: Missense Mutation Are these deleterious? Missense mutations code for a different amino acid. Sickle Cell Anemia Himalayan Mice and Mink Himalayan Mice and Mink Base-Pair Substitution: Nonsense Mutation Nonsense mutations change an amino acid codon into a stop codon. When the stop codon is encountered, translation stops, resulting in a truncated polypeptide. Nearly all truncated proteins are nonfunctional and unstable. Insertion/Deletion Mutations Insertions and deletions are additions or losses of nucleotide pairs in a gene. These mutations have a disastrous effect on the resulting protein more often than substitutions do. Insertion or deletion of nucleotides may alter the reading frame, producing a frameshift mutation. Insertion/Deletions: No Frameshift Can insertion or deletion of three bases (1 amino acid) really cause a problem? Example: cystic fibrosis Lecture Outline 1. Central Dogma a) Genotype and Phenotype b) Exceptions to the Central Dogma 2. The Genetic Code a) Five Properties of the Genetic Code 3. Mutations a) Point Mutations b) Chromosome-level Mutations Chromosome Mutations Chromosome mutations may change chromosome number or structure. What term is used to describe a cell that has too many or too few chromosomes? Aneuploidy What term is used to describe cells that have too many sets of chromosomes? Polyploidy Inversions and Reciprocal Translocations Inversion: A segment of a chromosome breaks off, flips around, and rejoins. Translocation: A section of a chromosome breaks off and becomes attached to another chromosome. Chromosomal Level Insertions / Deletions Deletion: A segment of a chromosome is lost. Duplication: A segment of a chromosome is present in multiple copies. Gene Duplication and Evolutionary Divergence Duplication and divergence results in the formation of new genes from duplicates of old ones. Gene family: a group of genes with related functions.