Download Chapter 15 – DNA to Proteins

How Genes Work
15
BIOLOGICAL SCIENCE
FOURTH EDITION
SCOTT FREEMAN
Lectures by Stephanie Scher Pandolfi
© 2011 Pearson Education, Inc.
Key Concepts
Most genes code for proteins.
DNA is transcribed to messenger RNA by RNA polymerase, and
then messenger RNA is translated to proteins by ribosomes. In
this way, genetic information is converted from DNA to RNA to
proteins.
Each amino acid in a protein is specified by a group of three bases
in messenger RNA.
© 2011 Pearson Education, Inc.
Key Concepts
Mutations are random changes in DNA, ranging in extent from
single bases to large chromosome regions, that may or may not
produce changes in the phenotype.
© 2011 Pearson Education, Inc.
Introduction
• While the work of early geneticists, including Mendel, Watson &
Crick, and others, illuminated the structure of DNA and genes, and
the method of inheritance, biologists still did not understand how
gene expression occurred.
– Gene expression is the process of translating the information in
DNA into functioning molecules within the cell.
© 2011 Pearson Education, Inc.
What Do Genes Do?
• Early advances showed that genes carry the instructions for making
and maintaining an individual.
• In order to infer what a particular gene does, George Beadle and
Edward Tatum proposed damaging a gene, creating a mutant, and
then observing the resulting effect on the mutant’s phenotype.
• Nonfunctioning alleles are now called knock-out, null, or loss-offunction alleles.
© 2011 Pearson Education, Inc.
The One-Gene, One-Enzyme Hypothesis
• To test their hypothesis, Beadle and Tatum damaged genes in the
bread mold Neurospora crassa, and observed that defects in
particular genes resulted in the mold’s inability to produce specific
proteins.
• The results of their experiments inspired their one-gene, oneenzyme hypothesis, which proposed that each gene contains the
information needed to make an enzyme.
© 2011 Pearson Education, Inc.
Testing the One-Gene, One-Enzyme Hypothesis
• Srb and Horowitz further tested the one-gene, one-enzyme
hypothesis by examining the production of the amino acid arginine
by N. crassa.
• Arginine is produced via a metabolic pathway requiring the action
of three different enzymes. Srb and Horowitz hypothesized that
different genes lead to the synthesis of each of the three enzymes.
© 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.
Testing the One-Gene, One-Enzyme Hypothesis
• To test their hypothesis, Srb and Horowitz used radiation to create
thousands of mutant individuals and then performed a genetic
screen, which allowed them to select those mutants incapable of
producing arginine.
• The results supported the one-gene, one-enzyme hypothesis.
– Three distinct mutants were produced, each deficient in one of
the three enzymes in the arginine metabolic pathway.
Biologists finally understood what most genes do: They contain
the instructions for making proteins.
© 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.
One-Gene-One-Enzyme Hypothesis
© 2011 Pearson Education, Inc.
The Central Dogma of Molecular Biology
• Francis Crick proposed that DNA is an information storage
molecule, and that the sequence of bases in DNA is a kind of code
in which different combinations of bases could specify the 20
amino acids.
• A particular stretch of DNA (a gene) contains the information to
specify the amino acid sequence of one protein.
• The information encoded in the base sequence of DNA is not
directly translated into the amino acid sequence of proteins.
© 2011 Pearson Education, Inc.
RNA—the Intermediary between Genes and Proteins
• François Jacob and Jacques Monod proposed that RNA molecules
act as a link between genes, found in the cell’s nucleus, and the
protein-manufacturing centers, located in the cytoplasm.
• Messenger RNA (mRNA) was found to carry information from
DNA to the site of protein synthesis.
• The enzyme RNA polymerase synthesizes RNA according to the
information provided by the sequence of bases in a particular
stretch of DNA.
© 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.
The Central Dogma
• The central dogma summarizes the flow of information in cells. It
states that DNA codes for RNA, which codes for proteins:
DNA  RNA  proteins
The sequence of bases in a particular stretch of DNA specifies the
sequence of bases in an RNA molecule, which specifies the
sequence of amino acids in a protein. In this way, genes ultimately
code for proteins.
© 2011 Pearson Education, Inc.
The Roles of Transcription and Translation
• DNA is transcribed to messenger RNA by RNA polymerase.
– Transcription is the process by which the hereditary
information in DNA is copied to RNA.
• The mRNA is then translated to protein.
– Translation is the process wherein the language of nucleic
acids, the order of the nucleotide bases, is converted to the
language of proteins, the order of amino acids.
© 2011 Pearson Education, Inc.
Visualizing the Central Dogma
DNA
(information storage)
Transcription
mRNA
(information carrier)
Translation
Proteins
(active cell machinery)
© 2011 Pearson Education, Inc.
The Central Dogma
• According to the central dogma, an organism’s genotype is
determined by the sequence of bases in its DNA, while its
phenotype is a product of the proteins it produces.
• Alleles of the same gene differ in their DNA sequence. Thus, the
proteins produced by different alleles of the same gene frequently
differ in their amino acid sequence.
© 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.
Exceptions to the Central Dogma
• Many genes code for RNA molecules that do not function as
mRNAs and are not translated into proteins.
– These other RNAs perform important functions in the cell.
• Sometimes information flows in the opposite direction—from RNA
back to DNA.
– For example, some viral genes are composed of RNA and use
reverse transcriptase, a viral polymerase, to synthesize a
DNA version of the virus’s RNA genes.
© 2011 Pearson Education, Inc.
The Genetic Code
• Once the pattern of information flow in a cell was determined,
biologists next strove to determine exactly how the sequence of
bases in a strand of mRNA codes for the sequence of amino acids
in a protein.
• The genetic code contains the rules that specify the relationship
between a sequence of nucleotide bases in DNA or RNA and the
corresponding sequence of amino acids in a protein.
© 2011 Pearson Education, Inc.
How Long Is a Word in the Genetic Code?
• George Gamow predicted that each word in the genetic code
contains three bases.
• As there are 20 amino acids and only four different RNA bases, a
three-base code is the least that could specify enough amino
acids—it could code for 4  4  4 = 64 different amino acids.
A three-base code provides more than enough messages to code
for all 20 amino acids. A three-base code is known as a triplet
code.
© 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.
How Long Is a Word in the Genetic Code?
• The triplet code is redundant, with some amino acids being
specified by more than one triplet code.
• The group of three bases that specifies a particular amino acid is
called a codon.
• Francis Crick and Sydney Brenner found that the reading frame
(sequence of codons) of a gene could be destroyed by mutation but
then restored if the total number of deletions or additions were
multiples of three.
© 2011 Pearson Education, Inc.
How Did Researchers Crack the Code?
• Marshall Nirenberg and Philip Leder devised a system for
synthesizing specific codons and were able to decipher the genetic
code by determining which of the 64 codons coded for each of the
20 amino acids.
– There is one start codon (AUG), which signifies the start of
the protein-encoding sequence in mRNA.
– There are three stop codons (UGA, UAA, and UAG) in the
genetic code that signal the end of the protein-coding sequence.
© 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.
Important Properties of the Code
• It is redundant.
– All amino acids except two are encoded by more than one
codon.
• It is unambiguous.
– One codon never codes for more than one amino acid.
• It is nearly universal.
– With a few minor exceptions, all codons specify the same
amino acids in all organisms.
• It is conservative.
– The first two bases are usually identical when multiple codons
specify the same amino acid.
© 2011 Pearson Education, Inc.
Using the Code
• Biologists can work forwards or backwards in the central dogma to:
1. Predict the codons and amino acid sequence encoded by a
particular DNA sequence.
2. Approximate the mRNA and DNA sequence that would
code for a particular sequence of amino acids.
© 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.
What Is the Molecular Basis of Mutation?
A mutation is any permanent change in an organism’s DNA. It is
a modification in a cell’s information archive—a change in its
genotype. Mutations create new alleles.
• There are different types of mutations.
– Point mutations result from a single base change.
– Chromosome-level mutations are larger in scale, often
resulting from the addition or deletion of chromosomes from
the individual’s karyotype.
© 2011 Pearson Education, Inc.
Point Mutations
• Point mutations occur when the DNA polymerase inserts the wrong
base into the newly synthesized strand of DNA.
– Results in a change in the DNA base sequence if the DNA
polymerase proofreading and mismatch repair systems fail.
• Point mutations may be:
– Missense, or replacement mutations.
– Result in changes in the amino acid sequence of the
encoded protein.
– Silent mutations.
– Does not change the amino acid sequence of the gene
product.
© 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.
Mutations Have Varying Effects on Organisms
• Mutations fall into one of three categories:
1. Beneficial mutations increase the fitness of the organism.
2. Neutral mutations do not affect an organism’s fitness.
─ Silent mutations are usually neutral.
3. Deleterious mutations decrease the fitness of the organism.
• Most mutations are neutral or slightly deleterious.
© 2011 Pearson Education, Inc.
Triplet Nature of the Genetic Code
© 2011 Pearson Education, Inc.
Chromosome-Level Mutations
• Chromosome-level mutations may involve changes in chromosome
number.
– Polyploidy is an increase in the number of each type of
chromosome.
– Aneuploidy is the addition or deletion of a chromosome.
• Chromosome composition can also change.
– Inversions occur when sections of a chromosome break and
rotate before rejoining the chromosome.
– Translocation occurs when a broken section of one
chromosome becomes attached to another chromosome.
• Chromosome-level mutations can be visualized via the karyotype
of a cell.
© 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.
© 2011 Pearson Education, Inc.