{ "cells": [ { "cell_type": "markdown", "metadata": {}, "source": [ "# Transcription and Translation" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "[OpenStax Biology Chapter 15: Genes and Proteins](http://cnx.org/contents/GFy_h8cu@9.87:7MmMR-pY@3/Introduction)" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "## Central Dogma of Molecular Biology" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "* Information flows from nucleic acids to proteins, but can not flow back\n", "
The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred back from protein to either protein or nucleic acid.\n", "
\n", "\n", "* DNA is *transcribed* into RNA \n", " * Think of transcription as copying from one *format* to another (i.e. spoken to written words)\n", " * Same language, different forms\n", " * DNA and RNA are both nucleic acids\n", "* RNA is *translated* into proteins\n", " * Think of translation as changing the language (i.e. English to Chinese)\n", " * RNA and proteins are made of different things\n", " * RNA is made of nucleotides\n", " * Proteins are made of amino acids.\n", "" ] }, { "cell_type": "markdown", "metadata": { "collapsed": true, "format": "row" }, "source": [ "## Transcription" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "* The process by which DNA is copied to RNA\n", "* RNA: Ribonucleic Acid\n", " * Uses Uracil (U) instead of Thymine (T)\n", " * Other nucleotides are the same\n", "* Many kinds of RNA\n", " * mRNA\n", " * messenger RNA\n", " * mRNA molecules are destined to be translated into proteins\n", " * single stranded copy of a segment of DNA\n", " * tRNA \n", " * transfer RNA\n", " * stably folded structure \n", " * Used in the translation of RNA to amino acids\n", " * rRNA\n", " * ribosomal RNA\n", " * structural and functional component of the ribosome\n", " * regulatory RNA\n", " * miRNA: micro RNA\n", " * siRNA: short interfering RNA\n", " * lncRNA: long noncoding RNA\n", " * snoRNA: small nucleolar RNA\n", "* Transcription is performed by *RNA Polymerase*\n", " * 5' to 3' synthesis, just like DNA\n", " * Copies one strand of DNA to RNA by homologous pairing to *template strand*\n", " * mRNA sequence is identical (with T->U changes) to *coding strand*\n", "* What to transcribe? How much?" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "## Translation" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "* The process by which mRNA is used to make a protein\n", "* Protein structure\n", " * Polymer of amino acids\n", " * Peptide chain\n", " * Polypeptide\n", " * Each amino acid has three main parts \n", " * Amine (-NH2) N end\n", " * Carboxylic acid (-COOH) C end\n", " * Variable side chain (R group)\n", " * side chain determines chemical and physical properties of the amino acid\n", " * large, small, positively or negatively charged, hydrophobic, etc.\n", " * amino acids are joined into polypeptides by connecting N to C \n", " * Like DNA & RNA, these are directional additions\n", " * Always add to the C-terminal end\n", " * Refer to proteins in N to C direction/order\n", " * 20 different amino acids are used in most biological systems \n", "" ] }, { "cell_type": "markdown", "metadata": {}, "source": [] }, { "cell_type": "markdown", "metadata": {}, "source": [ "## The Genetic Code" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "* Translation nucleotide sequence to amino acid sequence\n", " * How many nucleotides are needed to specify each of the 20 amino acids + 1 stop signal? \n", "\n", "* Codons\n", " * Groups of 3 nucleotides that translate to a single amino acid or stop signal.\n", " * Redundant code:\n", " * Most amino acids are encoded by multiple codons\n", " * redundancy is usually at the third position: wobble base" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "### The standard genetic code" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "adapted from Wikipedia\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "
1st
\n", "base		2nd base3rd
\n", "base
TCAG
TTTT(Phe/F) PhenylalanineTCT(Ser/S) SerineTAT(Tyr/Y) TyrosineTGT(Cys/C) CysteineT
TTCTCCTACTGCC
TTA(Leu/L) LeucineTCATAAStop (Ochre)TGAStop (Opal)A
TTGTCGTAGStop (Amber)TGG(Trp/W) Tryptophan    G
CCTTCCT(Pro/P) ProlineCAT(His/H) HistidineCGT(Arg/R) ArginineT
CTCCCCCACCGCC
CTACCACAA(Gln/Q) GlutamineCGAA
CTGCCGCAGCGGG
AATT(Ile/I) IsoleucineACT(Thr/T) Threonine        AAT(Asn/N) AsparagineAGT(Ser/S) SerineT
ATCACCAACAGCC
ATAACAAAA(Lys/K) LysineAGA(Arg/R) ArginineA
ATG[A](Met/M) MethionineACGAAGAGGG
GGTT(Val/V) ValineGCT(Ala/A) AlanineGAT(Asp/D) Aspartic acidGGT(Gly/G) GlycineT
GTCGCCGACGGCC
GTAGCAGAA(Glu/E) Glutamic acidGGAA
GTGGCGGAGGGGG
\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "\n", "
nonpolarpolarbasicacidic(stop codon)
" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "### Translation " ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "* Translation occurs at the ribosome \n", " * The ribosome is a complex of proteins and RNA\n", " * 2 major subunits\n", " * small subunit: 30S (prokaryote) or 40S (eukaryote)\n", " * large subunit: 50S (prokaryote) or 60S (eukaryote)\n", " * ribozyme (RNA enzyme)\n", " * ratcheting of mRNA\n", " * tRNA binding & fidelity checks\n", " * protein synthesis\n", " \n", " \n", "* Translation by tRNA adapters\n", " * Each codon corresponds to a particular tRNA molecule \n", " * tRNA has an anti-codon sequence complementary to the codon\n", " * end of tRNA is bound to amino acid\n", " * when corresponding tRNA is matched to a codon, the amino acid is transferred to the growing peptide chain\n", "\n", "* Initiation and termination of translation\n", " * Translation always starts with a Methionine\n", " * Encoded by ATG/AUG (usually)\n", " * Commonly referred to as the \"start\" codon\n", " * Methionine *is* ncluded in the resulting polypeptide\n", " * Translation terminates at a \"stop\" codon\n", " * Encoded by TAA/UAA, TAG/UAG, or TGA/UGA\n", " * Stop codons *do not* encode amino acids: the final amino acid of the polypeptide/protein is whatever came before the stop codon.\n", " * Implications:\n", " * The entire mRNA may not be translated!\n", " * 5' and 3' untranslated regions (UTRs) can have regulatory functions\n", " \n", "### Other complications\n", "* In Eukaryotes, mRNA are often modified after initial transcription \n", " * Primary transcript made up of two types of sequences: **exons** and **introns**\n", " * Exons are what remains in mature transcript after processing \n", " * Introns (intervening sequences) are removed\n", " * some cases in bacteria and archaea\n", "* Alternative codes\n", " * Full list of [alternative codes at NCBI](http://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi)\n", " * Notably, Mitochondria use an alternative code\n", " * Many other taxa have small variants\n", " \n", "* AUG is not the only start codon \n", " * Depending on organism, some alternatives are possible\n", " * In mitochondria, AUA and AUU \n", " * In bacteria, GUG and UUG\n", " * *At start position only*, these are still translated as Methionine\n" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "### Videos" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "[HHMI video on translation](http://www.hhmi.org/biointeractive/translation-basic-detail) \n", "[Advanced translation video](http://www.hhmi.org/biointeractive/translation-advanced-detail)" ] }, { "cell_type": "code", "execution_count": 16, "metadata": { "collapsed": false }, "outputs": [ { "data": { "image/jpeg": 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Pk/Wk5OYXoRMaxg3LquoY6lW8x3YE7J166mfEVUyDaxB9NEbndtaunG97HrsZ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\nEnj0hrZ6S+tCZqFMp4xPE76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"text/html": [ "\n", " \n", " " ], "text/plain": [ "" ] }, "execution_count": 16, "metadata": {}, "output_type": "execute_result" } ], "source": [ "from IPython.display import YouTubeVideo\n", "YouTubeVideo(\"ZNl1z6Lev1E\", width=\"560\")" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "* Other notes:\n", " * This genetic code is shared across all (known) life on earth, with only a few small variations\n", " * Evolved early in history of life\n", " * A \"frozen accident\"? Crick, 1968\n", " * Modeling of alternative codes suggest that this one is near optimal" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "### Interpretive Dance\n", "Produced in 1971 at Stanford. \n", "Introduced by future (1980) Nobel Prize winner Paul Berg. " ] }, { "cell_type": "code", "execution_count": 17, "metadata": { "collapsed": false }, "outputs": [ { "data": { "image/jpeg": 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