Download Gene Expression and Gene Regulation

Gene Expression and
Gene Regulation
The Link between Genes and Proteins
•At the beginning of the 20th century, Garrod
proposed:
– Genetic disorders such as alkaptonuria result from
biochemical alterations or “inborn errors of
metabolism”
•Using a yeast, Beadle and Tatum showed that
mutations:
– Can produce a loss of enzyme activity
– Can produce a mutant phenotype
– Genes-->Proteins--> Phenotype Nobel Prize 1958
The Genetic Code
• Information transferred from DNA to mRNA is encoded in a
set of three nucleotides (codons)
• Codons
– Encode the information for a specific amino acid in a protein. 3
nucleotides in 1 codon
• Of 64 possible codons, 61 code for amino acids, and 3 are
stop codons
• The codon AUG is a start codon and specifies methionine
The Genetic Code
9.4 The Flow of Genetic Information
 Transfer of information from the linear
sequence of nucleotides in DNA to the linear
sequence of amino acids in a protein occurs in
two steps:
– Transcription
– Translation
The Flow of Genetic Information
(contd.)
• Transcription
– Transfer of genetic information from the base
sequence of DNA to the base sequence of RNA,
mediated by RNA synthesis
• Translation
– Conversion of information encoded in the nucleotide
sequence of an mRNA molecule into the linear
sequence of amino acids in a protein
What is the
central The
Central
Dogma?
DNA
Transcription
pre-mRNA
mRNA processing
mRNA
Translation
Polypeptide
Cell
Cytoplasm
Nucleus
Interaction of Components
• Transcription and translation require the
interaction of
– Ribosomes,
– mRNA,
– tRNA,
– Amino acids,
– Enzymes, and
– Energy sources
Interaction of Components (contd.)
• Ribosomes are the sites on which protein
synthesis occurs
• tRNA molecules are adapters that recognize
amino acids and the nucleotide sequence in
mRNA.
– Each tRNA has one anticodon (the match to a
codon on a mRNA) and can only carry one type of
amino acid
Transcription
• Begins when DNA unwinds and one strand is
used as template to make a pre-mRNA
molecule
• Has three stages:
– Initiation
– Elongation
– Termination
ANIMATION: Transcription—A
molecular view
Transcription
Initiation and Termination
• Promoter region
– The region of a gene on a DNA molecule to which
RNA polymerase binds and initiates transcription
• Terminator Region
– The nucleotide sequence at the end of a gene that
signals the end of transcription
Transcription of a Gene
Gene region
5’ Promoter region
RNA polymerase, the enzyme that
catalyzes transcription
(a) RNA polymerase binds to a promoter in the DNA, along with
regulatory proteins (initiation). The binding positions the
polymerase near a gene in the DNA.
Only one strand of DNA provides a template for
transcription of mRNA.
Transcription of a Gene
Newly forming
RNA transcript
DNA template
winding up
DNA template
unwinding
(b) The polymerase begins to move along the DNA and unwind it. As
it does, it links RNA nucleotides into a strand of RNA in the order
specified by the base sequence of the DNA (elongation).
The DNA double helix rewinds after the polymerase passes. The
structure of the “opened” DNA molecule at the transcription site is
called a transcription bubble, after its appearance.
Transcription of a Gene
Transcription site
G
A
A
Growing RNA transcript
(c) What happened in the gene region? RNA polymerase catalyzed
the covalent bonding of many nucleotides to one another to form an
RNA strand. The base sequence of the new RNA strand is
complementary to the base sequence of its DNA template––a copy
of the gene.
G
Pre-mRNA processing
• Transcription produces large mRNA precursor
molecules called pre-mRNA
• Pre-mRNA is processed in the nucleus to
produce mature mRNA
Processing and Splicing mRNA
• Cap
– A modified base (guanine nucleotide) attached to
the 5’ end of eukaryotic mRNA molecules
• Poly-A tail
– A series of A nucleotides added to the 3’end of
mRNA molecules
Processing and Splicing mRNA
• Introns
– DNA sequences present in some genes that are
transcribed, but are removed during processing and
therefore are not present in mature mRNA
• Exons
– DNA sequences that are transcribed, joined with other
exons during mRNA processing, and translated into
the amino acid sequence of a protein
Unit of transcription
in DNA strandof mRNA
Processing
and Splicing
Exon
Intron
Exon
Intron
Exon
Transcription into pre-mRNA
Cap
Poly-A tail
Snipped out
Snipped out
Mature mRNA transcript
Alternative Splicing
Smooth-muscle
mRNA
pre-mRNA
Striated-muscle
mRNA
Exons
1–12
Mutations in Splicing Sites
• Splicing defects cause several human genetic
disorders
• One hemoglobin disorder, b-thalassemia, is
due to mutations at the exon/intron region
and lower splicing efficiency