Central Dogma BioL S103F PDF

Summary

These lecture notes cover the central dogma of molecular biology, focusing on DNA, RNA, and protein synthesis. Topics include transcription, translation, and the genetic code.

Full Transcript

BIOL S103F ESSENTIAL BIOLOGY CENTRAL DOGMA Week 8 Genes Control Phenotypic Traits through the Expression of Proteins 2    DNA specifies traits by dictating protein synthesis Proteins are the links between genotype & phenotype The molecular chain of command     DNA in the nucleus  RNA RNA in...

BIOL S103F ESSENTIAL BIOLOGY CENTRAL DOGMA Week 8 Genes Control Phenotypic Traits through the Expression of Proteins 2    DNA specifies traits by dictating protein synthesis Proteins are the links between genotype & phenotype The molecular chain of command     DNA in the nucleus  RNA RNA in the cytoplasm  protein Transcription  Synthesis of RNA under the direction of DNA Translation  Synthesis of proteins under the direction of RNA © 2015 Pearson Education Ltd Transcription produces genetic messages in the form of RNA Transcription of a gene occurs in 3 main steps 3 Direction of transcription Initiation RNA synthesis begins after RNA polymerase attaches to the promoter. Unused Unused strand strand of of DNA DNA RNA polymerase Terminator DNA DNA of gene Promoter – Binding site for RNA polymerase Newly formed RNA Template Template strand of of DNA DNA Elongation Direction of transcription Using the DNA as a template, RNA polymerase adds free RNA nucleotides one at a time. DNA strands reunite Free RNA nucleotide T C C A A U C CA A G G TT DNA strands separate Newly formed RNA strand grows Termination Terminator RNA synthesis ends when DNA RNA polymerase reaches the terminator DNA sequence. Completed RNA RNA polymerase detaches from the newly made RNA strand & the gene © 2015 Pearson Education Ltd Messenger RNA (mRNA) 4    Encodes amino acid sequences Conveys genetic messages from DNA  translation machinery of the cell  In prokaryotes  Occurs in the same place that mRNA is made  In eukaryotes  Eukaryotic RNA (pre-mRNA) is processed before leaving the nucleus as mRNA  Addition of 5’ cap & poly-A tail  RNA splicing  mRNA must exit the nucleus via nuclear pores to enter the cytoplasm Eukaryotic pre-mRNA has introns  Interrupt sequences that separate exons (the coding regions)  RNA splicing removes introns (intervening sequences) & joins exons (expressed sequences) to produce a continuous coding sequence Eukaryotic RNA is Processed before Leaving the Nucleus as mRNA 5 Different exons code for different domains in a protein RNA splicing © 2015 Pearson Education Ltd Alternative RNA Splicing 6   Some introns contain sequences that may regulate gene expression Some genes can encode > 1 kind of polypeptide, depending on which segments are treated as exons during splicing  Alternative RNA splicing  Number of proteins produced is >>> number of genes https://upload.wikimedia.org/wikipedia/commons/0/0a/DNA_alternative_splicing.gif DNA  RNA  Protein 7      Sequence of nucleotides in DNA provides a code for constructing a protein  Protein construction requires conversion of a nucleotide sequence to an amino acid sequence  Transcription rewrites the DNA code into RNA, using the same nucleotide “language” (complementary pairing) Flow of information from gene to protein is based on a triplet code Genetic instructions for the amino acid sequence of a polypeptide chain are written in DNA & RNA as a series of 3-base “words” called codons Translation switches the nucleotide “language” to the amino acid “language” Each amino acid is specified by a codon  64 (i.e. 43) codons are possible  Some amino acids have > 1 possible codon DNA A A A C C GG C A A A A Transcription RNA Translation U U U GG C C G U U U U Codon Polypeptide Amino acid © 2015 Pearson Education Ltd Genetic Code Dictates How Codons are Translated into Amino Acids 8   Genetic code is the amino acid translations of each of the nucleotide triplets  3 nucleotides specify 1 amino acid  61 codons correspond to amino acids  AUG  Codes for methionine (Met)  Signals the start of translation  3 “stop” codons signal the end of translation  UAA, UGA, UAG http://www.perkepi.com/codon/ The genetic code is  Redundant -- with > 1 codon for some amino acids  Unambiguous -- any codon for one amino acid does NOT code for any other amino acid  Nearly universal -- shared by organisms from the simplest bacteria to the most complex plants & animals Translation 9   Translation can be divided into the same 3 phases as transcription 1. Initiation 2. Elongation 3. Termination Elongation continues until    A stop codon in the mRNA reaches the A site of the ribosomes Completed polypeptide is freed from the ribosome 2 ribosomal subunits & other components in the assembly dissociate © 2015 Pearson Education Ltd tRNA Enzyme Transfer RNA (tRNA) ATP 10   Functions as an interpreter, converting the genetic message of mRNA  the language of proteins tRNA molecules carry 2 functions 1. Picking up the appropriate amino acid 2. Using a special triplet of bases (anticodon), to recognize the appropriate codons in the mRNA  The anticodon triplet is complementary to a codon triplet on mRNA A tRNA molecule, showing its polynucleotide strand and hydrogen bonding Amino acid attachment site Hydrogen bond RNA polynucleotide chain Anticodon A simplified representation of a tRNA Growing polypeptide tRNA molecules Ribosomes Exit tunnel EP 11     Ribosomes have 2 subunits  A smalls subunit  A large subunit Each subunit is composed of  Ribosomal RNAs  Proteins A Small subunit Translation occurs on the surface of the ribosome Ribosomes coordinate 1. Functioning of mRNA & tRNA 2. Synthesis of polypeptides Large subunit 5′ mRNA 3′ tRNA binding sites P site (Peptidyl-tRNA binding site) Exit tunnel A site (Aminoacyl-tRNA binding site) E site (Exit site) E P A mRNA binding site Large subunit Small subunit Growing polypeptide Next amino acid to be added to polypeptide chain Amino end mRNA tRNA E 3′ 5′  Ribosomal subunits come together during translation  Ribosomes have binding sites for mRNA & tRNAs Codons © 2015 Pearson Education Ltd Ribosomes 12   Ribosomes of bacteria & eukaryotes are very similar in function Those of eukaryotes are slightly larger & different in composition  Differences are medically significant  Certain antibiotic drugs can inactivate bacterial ribosomes while leaving eukaryotic ribosomes unaffected  e.g. Tetracycline & streptomycin are used to combat bacterial infections Second base of RNA codon UUU U Phe UCU A UAU Tyr First base of RNA codon A Cys U UCA UAA Stop UGA Stop UUG UCG UAG Stop UGG CUU CCU CAU CGU U CAC CGC C CGA Leu CUC Ser Leu CCC Pro CUA CCA CAA CUG CCG CAG CGG AUU ACU AAU AGU ACC AAC AUC lle AUA G UGU  UGC UCC His C G UAC UUC UUA 13 C Thr ACA AAG GUU GAU GCU GUG Arg Asn Lys Ser GCC Val AGG GCA GCG GGC GAA GAG GGA Glu GGG A Ans: DNA:GGTAAATGC RNA: CCAUUUACG a.a.: Pro-Phe-Thr G GGU GAC Ala U C Arg Let’s try! What amino acid sequence does the DNA sequence GGTAAATGC code for? G G AGC AGA A A U Asp GUC GUA Trp Gln AAA AUG Met or ACG start C Third base of RNA codon U Gly C A G © 2015 Pearson Education Ltd DNA transcription and translation 14  https://www.youtube.com/watch?v=8_f-8ISZ164 Control of Gene Expression 15     Gene regulation  Turning on & off of genes  In response to environmental changes Gene expression  Overall process of information flow from genes to proteins Control of gene expression  Allows cells to produce specific kinds of proteins when & where they are needed Our earliest understanding of gene control came from the study of E. coli  Proteins interacting with DNA turn prokaryotic genes ON/OFF in response to environmental changes Chromosome Structure & Chemical Modifications Can Affect Gene Expression 16    Differentiation  Involves cell specialization in structure & function  Controlled by turning specific sets of genes on/off Almost all cells in an organism contain an identical genome Differences between cell types  Not due to the presence of different genes  Due to selective gene expression Mutations 17    Any change in the nucleotide sequence of DNA Can involve  Large chromosomal regions  Just a single nucleotide pair 2 general categories  Nucleotide substitution  Nucleotide insertion / deletion Mutations 18 1. Nucleotide substitutions  Replace one nucleotide & its partner with another pair of nucleotides  Base substitutions may produce  Silent mutation  Have no effect at all (redundancy of genetic code)  Missense mutation  Change the amino acid coding  a different amino acid  Harmful  May lead to an improved protein that enhances the success of the mutant organism & its descendants  Nonsense mutation  Change an amino acid into a stop codon  a prematurely terminated protein Mutations 19 2. Nucleotide insertions / deletions of one or more nucleotides in a gene  Cause a frameshift mutation  Alters the reading frame (triplet grouping) of the genetic message  Leads to significant changes in amino acid sequence  Produces a nonfunctional polypeptide The fat cat ate the big rat. Tef atc ata tet heb igr at.

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