Please enable JavaScript.
Coggle requires JavaScript to display documents.
Chapter 16-17 The molecular basis of inheritance/ The Gene Expression…
Chapter 16-17
The molecular basis of inheritance/ The Gene Expression
The Flow of Genetic Information
The information content of genes is in the specific sequences of nucleotides
The DNA inherited by an organism leads to specific traits by dictating the synthesis of proteins
Proteins are the links between genotype and phenotype
Gene expression, the process by which DNA directs protein synthesis, includes two stages: transcription and translation
Genes specify proteins via transcription and translation
How was the fundamental relationship between genes and proteins discovered?
Evidence from the Study of Metabolic Defects
In 1902, British physician Archibald Garrod first suggested that genes dictate phenotypes through enzymes that catalyze specific chemical reactions
He thought symptoms of an inherited disease reflect an inability to synthesize a certain enzyme
Cells synthesize and degrade molecules in a series of steps, a metabolic pathway
Nutritional Mutants in Neurospora: Scientific Inquiry
George Beadle and Edward Tatum exposed bread mold to X-rays, creating mutants that were unable to survive on minimal media
Their colleagues Adrian Srb and Norman Horowitz identified three classes of arginine-deficient mutants
Each lacked a different enzyme necessary for synthesizing arginine
1 more item...
The Products of Gene Expression: A Developing Story
Not all proteins are enzymes, so researchers later revised the hypothesis: one gene–one protein
Many proteins are composed of several polypeptides, each of which has its own gene
Therefore, Beadle and Tatum’s hypothesis is now restated as the one gene–one polypeptide hypothesis
It is common to refer to gene products as proteins rather than polypeptides
Basic Principles of Transcription and Translation
RNA is the bridge between genes and the proteins for which they code
Transcription is the synthesis of RNA using information in DNA
Transcription produces messenger RNA (mRNA)
Translation is the synthesis of a polypeptide, using information in the mRNA
Ribosomes are the sites of translation
In prokaryotes, translation of mRNA can begin before transcription has finished
In a eukaryotic cell, the nuclear envelope separates transcription from translation
Eukaryotic RNA transcripts are modified through RNA processing to yield the finished mRNA
1 more item...
Cracking the Code
All 64 codons were deciphered in the early 1960s
Of the 64 triplets, 61 code for amino acids; 3 triplets are “stop” signals to end translation
The genetic code is redundant (more than one codon may specify a particular amino acid) but not ambiguous; no codon specifies more than one amino acid
Codons must be read in the correct reading frame (correct groupings) in order for the specified polypeptide to be produced
Evolution of the Genetic Code
The genetic code is nearly universal, shared by the simplest bacteria and the most complex animals
Genes can be transcribed and translated after being transplanted from one species to another
Mutations of one or a few nucleotides can affect protein structure and function
What Is a Gene? Revisiting the Question
The idea of the gene has evolved through the history of genetics
We have considered a gene as
-a discrete unit of inheritance
-a region of specific nucleotide sequence in a chromosome
-a DNA sequence that codes for a specific polypeptide chain
A gene can be defined as a region of DNA that can be expressed to produce a final functional product that is either a polypeptide or an RNA molecule
Mutations are changes in the genetic information of a cell
Point mutations are changes in just one nucleotide pair of a gene
The change of a single nucleotide in a DNA template strand can lead to the production of an abnormal protein
If a mutation has an adverse effect on the phenotype of the organism, the condition is referred to as a genetic disorder or hereditary disease
Types of Small-Scale Mutations
Point mutations within a gene can be divided into two general categories:
--Single nucleotide-pair substitutions
--Nucleotide-pair insertions or deletions
Substitutions
A nucleotide-pair substitution replaces one nucleotide and its partner with another pair of nucleotides
Silent mutations have no effect on the amino acid produced by a codon because of redundancy in the genetic code
Missense mutations still code for an amino acid, but not the correct amino acid
Nonsense mutations change an amino acid codon into a stop codon; most lead to a nonfunctional protein
Insertions and Deletions
1 more item...
Transcription is the DNA-directed synthesis of RNA: a closer look
Transcription is the first stage of gene expression
Molecular Components of Transcription
RNA synthesis is catalyzed by RNA polymerase, which pries the DNA strands apart and joins together the RNA nucleotides
The RNA is complementary to the DNA template strand
RNA polymerase does not need any primer
RNA synthesis follows the same base-pairing rules as DNA, except that uracil substitutes for thymine
The DNA sequence where RNA polymerase attaches is called the promoter
In bacteria, the sequence signaling the end of transcription is called the terminator
The stretch of DNA that is transcribed is called a transcription unit
Synthesis of an RNA Transcript
The three stages of transcription:
3 more items...
RNA Polymerase Binding and Initiation of Transcription
Promoters signal the transcription start point and usually extend several dozen nucleotide pairs upstream of the start point
Transcription factors mediate the binding of RNA polymerase and the initiation of transcription
The completed assembly of transcription factors and RNA polymerase II bound to a promoter is called a transcription initiation complex
A promoter called a TATA box is crucial in forming the initiation complex in eukaryotes
Elongation of the RNA Strand
As RNA polymerase moves along the DNA, it untwists the double helix, 10 to 20 bases at a time
Transcription progresses at a rate of 40 nucleotides per second in eukaryotes
A gene can be transcribed simultaneously by several RNA polymerases
Nucleotides are added to the 3′ end of the growing RNA molecule
Termination of Transcription
The mechanisms of termination are different in bacteria and eukaryotes
In bacteria, the polymerase stops transcription at the end of the terminator and the mRNA can be translated without further modification
1 more item...
16
Many proteins work together in DNA replication and repair
The relationship between structure and function is manifest in the double helix
Watson and Crick noted that the specific base pairing suggested a possible copying mechanism for genetic material
The Basic Principle: Base Pairing to a Template Strand
Since the two strands of DNA are complementary, each strand acts as a template for building a new strand in replication
In DNA replication, the parent molecule unwinds, and two new daughter strands are built based on base-pairing rules
Watson and Crick’s semiconservative model of replication predicts that when a double helix replicates, each daughter molecule will have one old strand (derived or “conserved” from the parent molecule) and one newly made strand
Competing models were the conservative model (the two parent strands rejoin) and the dispersive model (each strand is a mix of old and new)
DNA Replication: A Closer Look
The copying of DNA is remarkable in its speed and accuracy
More than a dozen enzymes and other proteins participate in DNA replication
2 more items...
Synthesizing a New DNA Strand
DNA polymerases require a primer to which they can add nucleotides
The initial nucleotide strand is a short RNA primer
This is synthesized by the enzyme primase
Primase can start an RNA chain from scratch and adds RNA nucleotides one at a time using the parental DNA as a template
The primer is short (5–10 nucleotides long), and the 3′ end serves as the starting point for the new DNA strand
Enzymes called DNA polymerases catalyze the synthesis of new DNA at a replication fork
Most DNA polymerases require a primer and a DNA template strand
The rate of elongation is about 500 nucleotides per second in bacteria and 50 per second in human cells
Each nucleotide that is added to a growing DNA strand is a nucleoside triphosphate
dATP supplies adenine to DNA and is similar to the ATP of energy metabolism
The difference is in their sugars: dATP has deoxyribose while ATP has ribose
As each monomer joins the DNA strand, via a dehydration reaction, it loses two phosphate groups as a molecule of pyrophosphate
Antiparallel Elongation
1 more item...
The DNA Replication Complex
The proteins that participate in DNA replication form a large complex, a “DNA replication machine”
The DNA replication machine may be stationary during the replication process
The proteins that participate in DNA replication form a large complex, a “DNA replication machine”
The DNA replication machine may be stationary during the replication process
Recent studies support a model in which DNA polymerase molecules “reel in” parental DNA and extrude newly made daughter DNA molecules
The exact mechanism is not yet resolved
Proofreading and Repairing DNA
DNA polymerases proofread newly made DNA, replacing any incorrect nucleotides
In mismatch repair of DNA, repair enzymes correct errors in base pairing
1 more item...
Life’s Operating Instructions
DNA is the genetic material
Early in the 20th century, the identification of the molecules of inheritance loomed as a major challenge to biologists
The Search for the Genetic Material: Scientific Inquiry
When T. H. Morgan’s group showed that genes are located on chromosomes, the two components of chromosomes—DNA and protein—became candidates for the genetic material
The role of DNA in heredity was first discovered by studying bacteria and the viruses that infect them
Evidence That DNA Can Transform Bacteria
The discovery of the genetic role of DNA began with research by Frederick Griffith in 1928
Griffith worked with two strains of a bacterium, one pathogenic and one harmless
When he mixed heat-killed remains of the pathogenic strain with living cells of the harmless strain, some living cells became pathogenic
He called this phenomenon transformation, now defined as a change in genotype and phenotype due to assimilation of foreign DNA
1 more item...
Evidence That Viral DNA Can Program Cells
More evidence for DNA as the genetic material came from studies of viruses that infect bacteria
Such viruses, called bacteriophages (or phages), are widely used in molecular genetics research
A virus is DNA (sometimes RNA) enclosed by a protective coat, often simply protein
1 more item...
Building a Structural Model of DNA: Scientific Inquiry
After DNA was accepted as the genetic material, the challenge was to determine how its structure accounts for its role in heredity
Maurice Wilkins and Rosalind Franklin were using a technique called X-ray crystallography to study molecular structure
Franklin produced a picture of the DNA molecule using this technique
Franklin’s X-ray crystallographic images of DNA enabled Watson to deduce that DNA was helical
The X-ray images also enabled Watson to deduce the width of the helix and the spacing of the nitrogenous bases
The pattern in the photo suggested that the DNA molecule was made up of two strands, forming a double helix
Watson and Crick built models of a double helix to conform to the X-rays and chemistry of DNA
Franklin had concluded that there were two outer sugar-phosphate backbones, with the nitrogenous bases paired in the molecule’s interior
Watson built a model in which the backbones were antiparallel (their subunits run in opposite directions)
1 more item...
In 1953, James Watson and Francis Crick introduced an elegant double-helical model for the structure of deoxyribonucleic acid, or DNA
Hereditary information is encoded in DNA and reproduced in all cells of the body
This DNA program directs the development of biochemical, anatomical, physiological, and (to some extent) behavioral traits
DNA is copied during DNA replication, and cells can repair their DNA
If chromosomes of germ cells became shorter in every cell cycle, essential genes would eventually be missing from the gametes they produce
An enzyme called telomerase catalyzes the lengthening of telomeres in germ cells
The shortening of telomeres might protect cells from cancerous growth by limiting the number of cell divisions
There is evidence of telomerase activity in cancer cells, which may allow cancer cells to persist
A chromosome consists of a DNA molecule packed together with proteins
The bacterial chromosome is a double-stranded, circular DNA molecule associated with a small amount of protein
Eukaryotic chromosomes have linear DNA molecules associated with a large amount of protein
In a bacterium, the DNA is “supercoiled” and found in a region of the cell called the nucleoid
In the eukaryotic cell, DNA is precisely combined with proteins in a complex called chromatin
Chromosomes fit into the nucleus through an elaborate, multilevel system of packing
Proteins called histones are responsible for the first level of packing in chromatin
Unfolded chromatin resembles beads on a string, with each “bead” being a nucleosome, the basic unit of DNA packaging
They are composed of two each of the four basic histone types, with DNA wrapped twice around the core of the eight histones
The N-termini (“tails”) of the histones protrude from the nucleosome
Nucleosomes, and especially their histone tails, are involved in the regulation of gene expression
Chromatin undergoes changes in packing during the cell cycle
At interphase, some chromatin seems to be organized into a 10-nm fiber, but much is compacted into a 30-nm fiber, through folding and looping
Interphase chromosomes occupy specific restricted regions in the nucleus, and the fibers of different chromosomes do not become entangled
1 more item...
Eukaryotic cells modify RNA after transcription
Enzymes in the eukaryotic nucleus modify pre-mRNA (RNA processing) before the genetic messages are dispatched to the cytoplasm
During RNA processing, both ends of the primary transcript are altered
Alteration of mRNA Ends
Each end of a pre-mRNA molecule is modified in a particular way
The 5′ end receives a modified nucleotide 5′ cap
The 3′ end gets a poly-A tail
These modifications share several functions
They seem to facilitate the export of mRNA to the cytoplasm
They protect mRNA from hydrolytic enzymes
They help ribosomes attach to the 5′ end
Split Genes and RNA Splicing
Most eukaryotic genes and their RNA transcripts have long noncoding stretches of nucleotides that lie between coding regions
These noncoding regions are called intervening sequences, or introns
The other regions are called exons because they are eventually expressed, usually translated into amino acid sequences
RNA splicing removes introns and joins exons, creating an mRNA molecule with a continuous coding sequence
In some cases, RNA splicing is carried out by spliceosomes
Spliceosomes consist of a variety of proteins and several small RNAs that recognize the splice sites
The RNAs of the spliceosome also catalyze the splicing reaction
Ribozymes
Ribozymes are catalytic RNA molecules that function as enzymes and can splice RNA
The discovery of ribozymes rendered obsolete the belief that all biological catalysts were proteins
Three properties of RNA enable it to function as an enzyme
It can form a three-dimensional structure because of its ability to base-pair with itself
Some bases in RNA contain functional groups that may participate in catalysis
RNA may hydrogen-bond with other nucleic acid molecules
The Functional and Evolutionary Importance of Introns
Some introns contain sequences that may regulate gene expression
Some genes can encode more than one kind of polypeptide, depending on which segments are treated as exons during splicing
This is called alternative RNA splicing
Consequently, the number of different proteins an organism can produce is much greater than its number of genes
Translation is the RNA-directed synthesis of a polypeptide: a closer look
Genetic information flows from mRNA to protein through the process of translation
Molecular Components of Translation
A cell translates an mRNA message into protein with the help of transfer RNA (tRNA)
tRNAs transfer amino acids to the growing polypeptide in a ribosome
Translation is a complex process in terms of its biochemistry and mechanics
The Structure and Function of Transfer RNA
Each tRNA molecule enables translation of a given mRNA codon into a certain amino acid
Each carries a specific amino acid on one end
Each has an anticodon on the other end; the anticodon base-pairs with a complementary codon on mRNA
A tRNA molecule consists of a single RNA strand that is only about 80 nucleotides long
Flattened into one plane to reveal its base pairing, a tRNA molecule looks like a cloverleaf
Because of hydrogen bonds, tRNA actually twists and folds into a three-dimensional molecule
tRNA is roughly L-shaped with the 5' and 3' ends both located near one end of the structure
The protruding 3' end acts as an attachment site for an amino acid
Accurate translation requires two steps
First: a correct match between a tRNA and an amino acid, done by the enzyme aminoacyl-tRNA synthetase
Second: a correct match between the tRNA anticodon and an mRNA codon
Flexible pairing at the third base of a codon is called wobble and allows some tRNAs to bind to more than one codon
Ribosome Association and Initiation of Translation
The start codon (AUG) signals the start of translation
First, a small ribosomal subunit binds with mRNA and a special initiator tRNA
Then the small subunit moves along the mRNA until it reaches the start codon
Proteins called initiation factors bring in the large subunit that completes the translation initiation complex
Elongation of the Polypeptide Chain
During elongation, amino acids are added one by one to the C-terminus of the growing chain
Each addition involves proteins called elongation factors
Elongation occurs in three steps: codon recognition, peptide bond formation, and translocation
Energy expenditure occurs in the first and third steps
3 more items...
Making Multiple Polypeptides in Bacteria and Eukaryotes
Multiple ribosomes can translate a single mRNA simultaneously, forming a polyribosome (or polysome)
Polyribosomes enable a cell to make many copies of a polypeptide very quickly
A bacterial cell ensures a streamlined process by coupling transcription and translation
In this case the newly made protein can quickly diffuse to its site of function
In eukaryotes, the nuclear envelope separates the processes of transcription and translation
RNA undergoes processing before leaving the nucleus
Termination of Translation
Elongation continues until a stop codon in the mRNA reaches the A site of the ribosome
The A site accepts a protein called a release factor
The release factor causes the addition of a water molecule instead of an amino acid
This reaction releases the polypeptide, and the translation assembly comes apart
Completing and Targeting the Functional Protein
Often translation is not sufficient to make a functional protein
Polypeptide chains are modified after translation or targeted to specific sites in the cell
Protein Folding and Post-Translational Modifications
1 more item...
Targeting Polypeptides to Specific Locations
1 more item...
The Structure and Function of Ribosomes
Ribosomes facilitate specific coupling of tRNA anticodons with mRNA codons in protein synthesis
The two ribosomal subunits (large and small) are made of proteins and ribosomal RNA (rRNA)
Bacterial and eukaryotic ribosomes are somewhat similar but have significant differences
Some antibiotic drugs specifically target bacterial ribosomes without harming eukaryotic ribosomes
A ribosome has three binding sites for tRNA
The P site holds the tRNA that carries the growing polypeptide chain
The A site holds the tRNA that carries the next amino acid to be added to the chain
The E site is the exit site, where discharged tRNAs leave the ribosome
Building a Polypeptide
The three stages of translation:
3 more items...
All three stages require protein “factors” that aid in the translation process
Energy is required for some steps, too
The basis for these rules was not understood until the discovery of the double helix