AP Biology Ch. 17 From Gene to Protein

How Genes Control Metabolism The study of metabolic defects provided evidence that genes specify proteins. Garrod (1909) suggested that genes dictate phenotypes through enzymes that catalyze reactions. Some inherited diseases result from the inability to produce certain enzymes. Ex) alkaptonuria Specific genes direct production of specific enzymes.

One Gene-One Enzyme Hypothesis Beadle and Tatum studied the relationship between genes and enzymes by studying auxotrophs (nutritional mutants) They determined that the mutants lacked certain enzymes needed to produce necessary nutrients from the food source. One gene-one enzyme hypothesis: The function of a gene is to dictate the production of a specific enzyme. This was later modified to one-gene, one-polypeptide. In most cases, a gene determines the amino acid sequence of a polypeptide chain.

RNA- ribonucleic acid RNA links DNA’s genetic instructions for making proteins to the process of protein synthesis. It copies or transcribes the message from DNA and then translates that message into protein. RNA differs from DNA in the following ways: it has ribose instead of deoxyribose, uracil instead of thymine, and it is a single-stranded molecule.

Transcription and Translation Transcription and translation are the two main processes linking gene to protein. Both nucleic acids and proteins are informational polymers with linear sequences of monomers—nucleotides and amino acids, respectively.

Transcription Transcription is the synthesis of RNA using a DNA template. A gene’s unique nucleotide sequence is transcribed from DNA to a complementary nucleotide sequence in mRNA. mRNA carries this transcript to the ribosomes for translation into protein to take place.

Translation Translation is the synthesis of a polypeptide, which occurs under the direction of mRNA. The linear sequence of bases in mRNA is translated into the linear sequence of amino acids in a polypeptide. Process occurs on ribosomes (composed of rRNA) in the cytoplasm

The Genetic Code The flow of information from gene to protein is based on a triplet code. Codons are three-nucleotide sequences that specify which amino acids (61 codons) will be added to the growing polypeptide. Codons can also signal when translation terminates (3 codons). The codon for methionine (AUG) acts as a translational start signal.

Genetic code is universal The genetic code must have evolved early in the history of life, and is shared by bacteria as well as complex plants and animals. Because diverse forms of life share the same genetic code, it is possible to program one species to produce proteins characteristic of another species. Tobacco w/ firefly genes

Template strand Transcription is the DNA-directed synthesis of RNA. For each gene, only one of the two DNA strands (template strand) is transcribed. The complementary nontemplate strand is the parent strand for making a new template when DNA replicates. mRNA is complementary to the DNA template from which it is transcribed.

Template, cont. RNA synthesis on a DNA template is catalyzed by RNA polymerase. Base-pairing rules are followed, except that in RNA, uracil substitutes for thymine. Promoters signal the initiation of RNA synthesis, and transcription factors help eukaryotic RNA polymerase recognize promoter sequences. Transcription continues until a particular RNA sequence signals termination.

Stages of transcription Initiation- RNA polymerase binds to the promoter, DNA strands unwind, enzyme initiates RNA synthesis. Elongation- Polymerase moves downstream, unwinding the DNA and elongating the RNA transcript. DNA strands re-form a double helix. Termination- Polymerase transcribe a terminator sequence. RNA is released, and polymerase detaches from the DNA.

Eukaryotes: RNA editing Eukaryotic cells modify RNA after transcription. mRNA molecules are processed before leaving the nucleus by modification of their ends and by RNA splicing. Most eukaryotic genes have introns (noncoding regions) and exons (coding regions). In RNA splicing, introns are removed and exons are joined.

RNA processing: addition of the 5’cap And poly(A) tail

RNA splicing: introns are excised and exons are Spliced together

Exons and proteins In a number of genes, different exons code for separate domains of the protein product. Each domain, an independently folding part of the protein, performs a different function. New proteins can evolve by exon shuffling among genes.

Protein synthesis: Translation After picking up specific amino acids, tRNA molecule line up by means of their anticodon triplets at complementary codons on mRNA. The attachment of amino acids to its particular tRNA is an ATP-driven process. Ribosomes coordinate the three stages of translation: initiation, elongation, and termination.

Transfer RNA (tRNA) Molecules of tRNA are not identical. Each type of tRNA links a particular mRNA codon with a particular amino acid. The tRNA bears an anticodon which base pairs with the codon on the mRNA. For example, if the mRNA codon is UUU (phenylalanine), the anticodon on tRNA would be AAA and it would carry phenylalanine at its other end.

Ribosomes Each ribosome is composed of two subunits made of protein and ribosomal RNA (rRNA). Ribosomes have a binding site for mRNA; P and A sites that hold tRNA as amino acids are added to the polypeptide chain. and an E site for release of tRNA. Several ribosomes can work on a single mRNA molecule at the same time, forming a polyribosome.

Stages of Translation Ribosomes coordinate the three stages of translation: initiation, elongation, and termination Initiation: ribosomal subunit binds to a molecule of mRNA, initiator tRNA pairs with the start codon, AUG. This tRNA carries the amino acid methionine. Arrival of a large ribosomal subunit completes the initiation complex.

Initiation of translation!

Translation: Elongation Elongation adds amino acids to the polypeptide chain. Codon recognition, peptide bond formation, and translocation are the steps.

Elongation: Fill, bond, release and shift!

Translation: Termination Elongation continues until a “stop” codon in the mRNA is reached. A protein called a release factor binds to the stop codon, causing the addition of a water molecule instead of an amino acid to the polypeptide chain. This frees the polypeptide from the ribosome.

Termination of translation.

Signal peptides Free ribosomes in the cytosol initiate the synthesis of all proteins. Proteins needed for membranes, or to be exported from the cell, complete their synthesis when the ribosomes making them attach to the ER. Signal-recognition particles (SRP) binds to the leading end of the polypeptide chain, allowing the ribosome to bind to the ER. Other signal sequences target proteins for chloroplasts and mitochondria.

Protein synthesis: Prokaryotes vs. Eukaryotes Prokaryotes lack nuclei, so DNA is not segregated from ribosomes. Transcription and translation occur in rapid succession. Eukaryotes have nuclear envelopes that segregate transcription in the nucleus from translation in the cytoplasm. mRNA is modified extensively before it moves from the nucleus to the cytoplasm where translation occurs (RNA processing)

Coupled transcription and translation in bacteria

Point mutations Point mutations are changes in one base pair of DNA. Substitutions can cause missense (wrong codon, wrong amino acid) or nonsense (codes for stop signal) mutations. Insertions or deletions can produce frameshift mutations that disrupt the mRNA reading frame “downstream” of the mutation. Spontaneous mutations can occur during DNA replication or repair, sometimes caused by chemical and physical mutagens.

Point mutation: substitution causes sickle-cell