CHAPTER 10 Molecular Biology of the Gene

BIOLOGYCONCEPTS & CONNECTIONS

Fourth Edition

Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings

Neil A. Campbell • Jane B. Reece • Lawrence G. Mitchell • Martha R. Taylor

From PowerPoint® Lectures for Biology: Concepts & Connections

CHAPTER 10Molecular Biology of the Gene

Modules 10.6 – 10.16


• The information constituting an organism’s genotype is carried in its sequence of bases

THE FLOW OF GENETIC INFORMATION FROM DNA TO RNA TO PROTEIN

10.6 The DNA genotype is expressed as proteins, which provide the molecular basis for phenotypic traits


• A specific gene specifies a polypeptide

– The DNA is transcribed into RNA, which is translated into the polypeptide

Figure 10.6A

DNA

RNA

Protein

TRANSCRIPTION

TRANSLATION


The Evolution of Crick’s Central Dogma from the 1950s to today

1950’s DNA RNA Protein

DNA RNA Poly-peptide

Splicing

AlternativeSplicing

Phosphorylation

Glycosylation

Methylation

Acetylation

1980’s

DNA RNA Poly-peptide

SplicingAlternative

SplicingOther catalyticregulator RNAs

MicroRNAsEditing

ConformationalIsomers

Phosphorylation

Glycosylation

Methylation

Acetylation

Other

Histonemodifications

Other epigeneticfactors

Today


• The “words” of the DNA “language” are triplets of bases called codons

– The codons in a gene specify the amino acid sequence of a polypeptide

10.7 Genetic information written in codons is translated into amino acid sequences


Figure 10.7

DNA molecule

Gene 1

Gene 2

Gene 3

DNA strand

TRANSCRIPTION

RNA

Polypeptide

TRANSLATIONCodon

Amino acid


• Virtually all organisms share the same genetic code

10.8 The genetic code is the Rosetta stone of life

Figure 10.8A


• An exercise in translating the genetic code

Figure 10.8B

Startcodon

RNA

Transcribed strand

StopcodonTranslation

Transcription

DNA

Polypeptide

Template strand or antisense - strand

Coding Strand orSense + strand


10.9 Transcription produces genetic messages in the form of RNA

Figure 10.9A

RNApolymerase

RNA nucleotide

Direction oftranscription

Newly made RNA

Templatestrand of DNA

In eukaryotes, RNA poly 1Synthesizes rRNA, II synthesizes mRNA, and III synthesizestRNA. RNA poly. Has 5Subunits: 2 alpha bind reg-ulatory subunits, 1 beta binds the DNA template,1 beta binds thenucleosides, and one sigmarecognizes the promoterand initiates synthesis.


RNA polymerase I is responsible for transcribing RNA that becomes structural components of the ribosome. Pol 1 synthesizes a pre-rRNA 45S, which matures into 28S, 18S and 5.8S rRNAs which will form the major RNA sections of the ribosome.

RNA polymerase II transcribes protein-encoding genes, or messenger RNAs, which are the RNAs that get translated into proteins. Also, most snRNA (splicing) and microRNAs (RNAi). This is the most studied type, and due to the high level of control required over transcription a range of transcription factors are required for its binding to promoters.

RNA polymerase III transcribes a different structural region of the ribosome (5s), transfer RNAs, which are also involved the translation process, as well as non-protein encoding RNAs.

The enzymes of transcription

http://en.wikipedia.org/wiki/RRNA

http://en.wikipedia.org/wiki/Ribosome

http://en.wikipedia.org/wiki/SnRNA

http://en.wikipedia.org/wiki/MicroRNA

http://en.wikipedia.org/wiki/Transcription_factor


• In transcription, the DNA helix unzips

– RNA nucleotides line up along one strand of the DNA following the base-pairing rules at the promoter. A regulatory protein binds at -25 binds the TATAAAA box.

– This either allows the Polymerase to transcribe or not. Many other protein factors comprise the transcription complex.

– 50 nucleotides/sec

– 12 bases in the bubble

– No proofreading enzymes like DNA

– The single-stranded messenger RNA peels away and the DNA strands rejoin after GC hairpin forming region.

RNA polymerase

DNA of gene

PromoterDNA Terminator

DNAInitiation

Elongation

Termination

Area shownin Figure 10.9A

GrowingRNA

RNApolymerase

Completed RNA

Figure 10.9Bhttp://www.johnkyrk.com/DNAtranscription.html

http://www.johnkyrk.com/DNAtranscription.html


• Noncoding segments called introns are spliced out

• A cap and a tail are added to the ends

• 5” cap is a guanosine nucleotide connected to the mRNA via an unusual 5' to 5' triphosphate linkage. This guanosine is methylated on the 7' position directly after capping in vivo by a methyl transferase.

• The addition of adenine nucleotides to the 3′ end of messenger ribonucleic acid molecules during posttranscriptional modification

10.10 Eukaryotic RNA (hnRNA) is processed before leaving the nucleus

Figure 10.10

DNA

RNAtranscriptwith capand tail

mRNA

Exon Intron IntronExon Exon

TranscriptionAddition of cap and tail

Introns removed

Exons spliced together

Coding sequenceNUCLEUS

CYTOPLASM

Tail

Cap


Alternative splicing


• In the cytoplasm, a ribosome attaches to the mRNA and translates its message into a polypeptide

• The process is aided by transfer RNAs

10.11 Transfer RNA molecules serve as interpreters during translation

Figure 10.11A

Hydrogen bond

Amino acid attachment site

RNA polynucleotide chain

Anticodon


• Each tRNA molecule has a triplet anticodon on one end and an amino acid attachment site on the other

Figure 10.11B, C

Anticodon

Amino acidattachment site


10.12 Ribosomes build polypeptides

Figure 10.12A-C

Codons

tRNAmolecules

mRNA

Growingpolypeptide

Largesubunit

Smallsubunit

mRNA

mRNAbindingsite

P site A site

P A

Growingpolypeptide

tRNA

Next amino acidto be added topolypeptide


10.13 An initiation codon marks the start of an mRNA message

Figure 10.13A

End

Start of genetic message


• mRNA, a specific tRNA, and the ribosome subunits assemble during initiation

Figure 10.13B

1

Initiator tRNA

mRNA

Startcodon Small ribosomal

subunit

2

P site

Largeribosomalsubunit

A site


• The mRNA moves a codon at a time relative to the ribosome

– A tRNA pairs with each codon, adding an amino acid to the growing polypeptide

10.14 Elongation adds amino acids to the polypeptide chain until a stop codon terminates translation


Figure 10.14

1 Codon recognition

Amino acid

Anticodon

AsiteP site

Polypeptide

2 Peptide bond formation

3 Translocation

Newpeptidebond

mRNAmovement

mRNA

Stopcodon


1. Initiation


• The sequence of codons in DNA spells out the primary structure of a polypeptide

– Polypeptides form proteins that cells and organisms use

10.15 Review: The flow of genetic information in the cell is DNARNAprotein


• Summary of transcription and translation

Figure 10.15

1Stage mRNA istranscribed from aDNA template.

Anticodon

DNA

mRNARNApolymerase

TRANSLATION

Enzyme

Amino acid

tRNA

InitiatortRNA

Largeribosomalsubunit

SmallribosomalsubunitmRNA

Start Codon

2Stage Each amino acid attaches to its proper tRNA with the help of a specific enzyme and ATP.

3Stage Initiation of polypeptide synthesis

The mRNA, the first tRNA, and the ribosomal subunits come together.

TRANSCRIPTION


Figure 10.15 (continued)

4Stage ElongationGrowingpolypeptide

Codons

5Stage Termination

mRNA

Newpeptidebondforming

Stop Codon

The ribosome recognizes a stop codon. The poly-peptide is terminated and released.

A succession of tRNAs add their amino acids to the polypeptide chain as the mRNA is moved through the ribosome, one codon at a time.

Polypeptide


• Mutations are changes in the DNA base sequence

– These are caused by errors in DNA replication or by mutagens

– The change of a single DNA nucleotide causes sickle-cell disease

10.16 Mutations can change the meaning of genes


Figure 10.16A

Normal hemoglobin DNA

mRNA

Normal hemoglobin

Glu

Mutant hemoglobin DNA

mRNA

Sickle-cell hemoglobin

Val


• Types of mutations

Figure 10.16B

mRNANORMAL GENE

BASE SUBSTITUTION

BASE DELETION

Protein Met Lys Phe Gly Ala

Met Lys Phe Ser Ala

Met Lys Leu Ala His

Missing

Missense-mutation causing a change in aa.Nonsense-mutation causing a premature stop codon

Causes a “frame shift”

CHAPTER 10 Molecular Biology of the Gene

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