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PSYC 3102: Introduction to Behavioral Genetics Tuesday 9/18/01 The 5 Steps of Protein Synthesis 1.Photocopying or Transcription - Transcription factors enhance or inhibit transcription - The DNA strands separate - Nuclear RNA (nRNA) is synthesized from one of the DNA strands - The procedure is performed chemically by a series of enzymes (transcription stuff) that latches on to the DNA, splits it down the middle, and starts synthesis of RNA 2. Editing or Post-Transcriptional Modification - Introns (junk DNA in between sections of coding sequence that is removed) are spliced out - Exons (coding sequence, message/blueprint that is kept) are spliced together - Gives messenger RNA (mRNA) - Number of introns varies by gene (ex: amyloid precursor protein has 25 introns) 3. Transportation - mRNA leaves the nucleus - mRNA is transported to the endoplasmic reticulum - mRNA attaches itself to the ribosome 4. Translation Terms: - Amino Acid: the basic building block of protein - Polypeptide Chain: series of amino acids linked by peptide bonds (think of box cars linked together) - Protein: one or more polypeptide chains joined and folded in a 3D configuration (folds occur due to electrical charges of amino acids) - Codon: 3 letter nucleotide sequence in messenger RNA that codes for an amino acid (can also refer to a 3 letter sequence in DNA as well) - Transfer RNA (tRNA) resembles a 4-leaf clover and carries an amino acid Three nucleotides called an anti-codon serve as a bar code to tell what amino acid it carries Anti-codons are specific for an amino acid The tRNA binds to the mRNA at the anti-codon The amino acid carried by the tRNA attaches to the polypeptide chain The mRNA moves through the ribosome The process continues until a long chain of amino acids called a polypeptide is formed 5. Post-Translational Modification or Final Assembly - - Can mean a whole flock of things What always happens: chain folds back on itself (chemical attractions cause loops and folds) and becomes 3-dimensional and is an active biological molecule What might happen: o chain gets sliced up and becomes different things o chains get spliced together ex: the hemoglobin molecule (in red blood cells, transports oxygen from the lungs to target tissues) is made up of 2 polypeptide chains and 2 polypeptide chains, the products of two different genes o chains get spliced together with different molecules ex: adding a sugar makes a glycoprotein, adding a fat (lipid) makes a lipoprotein Even if a gene is transcribed and etc., something can come in and degrade the final product before it can be used, essentially shutting things off DNA Directionality of DNA is five prime (5’) to three prime (3’) There are certain regions called promoter regions in DNA that are recognized by the transcription stuff and where it latches on to start transcription Cap Site signals to start transcription Initiation Codon signals translation to start There are certain nucleotide sequences that indicate the beginning and ends of introns Stop Codons signals the stop of translation PolyA Tail may help prevent the RNA from degrading when it leaves the nucleus The gene has the blueprint, recognition sites, punctuation marks, etc. 4 letter alphabet; 3 letter words; there are no spaces, but codons can also act as punctuation marks O blood type example Copying error mutation occurred, creating an early stop codon Translation stops before the proper peptide is full made Was not a detrimental error, in fact has shown to give slight protection from peptic ulcers Protein Folding Ex: Hemoglobin carries oxygen through blood, oxygen atoms latch to iron atoms Protein folding is one of the most difficult problems to solve in molecular biology (can’t predict) Creates a 3D lock which determines molecular binding, the 3D shape is determined by folding Too many possibilities, scientists can’t predict IBM Super Computer has been designed to figure out protein folding Organization of Hemoglobin Genes Chromosome 11: β cluster **Has PSEUDO-GENES: sections very similar to a real gene, but doesn’t get transcribed or translated** Chromosome 16: α cluster; 2 genes; some sections related to fetal hemoglobin Messed up Genome 90% of nucleotides not ‘used’ -- Pseudogenes; introns; junk; errors/mutations Why? (important!) EVOLUTION - Doesn’t matter how it gets done, just so it does get done - Doesn’t ‘care’ about anything but reproduction, consequently there is no need to make things simple unless it interferes with the reproductive system, so junk gets carried on (eg. pseudo genes in the genome) - When we talk about human behavior, remember that it is as complicated as the genome, it doesn’t have to make sense, it is NOT simple or readily explainable Chapter 4 – Genetic Regulation – Developmental Genetics – EpiGenesis Background We start as a single fertilized egg which divides into identical cells So why aren’t we born as blobs of identical cells? Why do we stop growing? Every cell has identical DNA, so what makes cells different? Genes are not operating in the same places in the same manner Certain genes are turned on, others are turned off Development is an orchestration of genes being turned on and off Development is dynamic, not static What forces underly the dynamics? Mechanisms Methylation Occurs when a methyl group is added to DNA When there is enough methyl groups attached, it turns the gene off and makes it difficult to transcribe Some (but not all) methylations are reversible Abnormal methylation can lead to problems - Ex: FMR1 – hypermethylation leads to Fragile X syndrome; which is the leading Mendelian (single gene) disorder that causes mental retardation RNA Splicing One gene can result in a large number of different polypeptides Gene: Exon 1 Exon 2 Exon 3 Exon 4 Sometimes the mRNA will look like this: Other times it will look like this: ~20% of genes can do this Ex: APP (amyloid protein precursor) can produce 3 or 4 different polypeptides It is thought, but not known, that this is especially important for the CNS, as it is the most biochemically complex organ we have, the vast numbers of proteins may be due to splicing Ex1 Ex1 Ex2 Ex2 Ex3 Ex4