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Molecular Biology in a Nutshell (via UCSC Genome Browser) 02-223 Personalized Medicine: Understanding Your Own Genome Fall 2014
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DNA Double-stranded helix made up of the nucleotides A, C, G, and T Sugar in its nucleotides is deoxyribose Nucleotides form A–T and G–C base pairs across the helix
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Central Dogma: How the Information in DNA is Expressed DNA (Sequence of A, T, C, G’s ) (Sequence of A, U, C, G’s) Gene Transcription Protein (Sequence of amino acids ) Translation Nearly universal across all species!
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Genes In the recent human Encyclopedia of DNA elements (ENCODE) project – ~20,000 protein-coding genes were studies, which covers 2.94% of the genome – Non-protein coding regions of the genome? >80% of the genome is functional as regulatory sequences, based on the analysis of ENCODE data http://www.nature.com/encode/#/threads
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RNA RNA is similar to DNA, except that: – it is usually single-stranded – Sequence of A, U, C, G it has U in place of T, compared to DNA – the sugar in RNA nucleotides is ribose instead of deoxyribose – Protein-coding RNA: mRNA Non-protein-coding RNA
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Transcription Transcription begins with binding by RNA polymerase at a promoter region of DNA. The subunit is responsible for promoter recognition (in bacteria). Once initiation has been completed with the synthesis of the first 8–9 nucleotides, sigma ( ) dissociates and elongation proceeds with the core enzyme.
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Prokaryote vs Eukaryote Genomes Eukaryotic mRNAs require processing to produce mature mRNAs. – Introns (intervening sequences) are regions of the initial RNA transcript that are not expressed in the amino acid sequence of the protein. – Introns are removed by splicing and the exons (expressed) are joined together in the mature mRNA. The size of the mature mRNA is usually much smaller than that of the initial RNA. Prokaryote genomes do not have introns
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Splicing out the Introns
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Transcription in Eukaryotes: Introns and Exons
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Transcription Has Been Visualized by Electron Microscopy
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Central Dogma
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RNA derived from complementary bases in DNA In mRNA, triplet codons specify 1 amino acid
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Genetic Code for Translation Genetic code is degenerate, with many amino acids specified by more than one codon. Only tryptophan and methionine are encoded by a single codon. The genetic code shows order in that chemically similar amino acids often share one or two middle bases in the triplets encoding them.
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Initiator and Termination Codons Termination codons: UAG, UAA, and UGA do not code for any amino acid. Initiator codon: AUG is the only codon to encode for methionine.
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Synonymous and Nonsynonymous Mutations Synonymous mutations: mutations that does not cause the protein code to change Nonsynonymous mutations: mutations that cause the protein code to change
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Summary Central dogma – Transcription of DNA to mRNA – Translation of mRNA to proteins Introns/Exons in eukaryote genomes
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