Mutations:Mutations:

are changes to the genetic are changes to the genetic information of a cellinformation of a cell

are responsible for the huge are responsible for the huge diversity among living thingsdiversity among living things

are the ultimate source of new genesare the ultimate source of new genes

Point Mutations:Point Mutations: Changes in a single base pair of a gene can Changes in a single base pair of a gene can

lead to the production of an abnormal lead to the production of an abnormal protein:protein:Wild-type HemoglobinWild-type Hemoglobin Mutant Mutant

HemoglobinHemoglobin3’-CTT-5’3’-CTT-5’ 3’-C3’-CAAT-5’T-5’5’-GAA-3’5’-GAA-3’ 5’-G5’-GTTA-3’A-3’

5’-GAA-3’5’-GAA-3’ 5’-G5’-GUUA-3’A-3’= Normal hemoglobin= Normal hemoglobin == Sickle-cell Sickle-cell

hemoglobinhemoglobin

DNA DNA

mRNA mRNA

Types of Point Types of Point Mutations:Mutations:I. I. Base-pairBase-pair

substitutionssubstitutions – one base pair – one base pair replaced by another pairreplaced by another pair

1. 1. Silent mutationsSilent mutations – – due to due to redundancy of the genetic code, there redundancy of the genetic code, there is no effect on the encoded proteinis no effect on the encoded proteinCC

GGGC

= WT DNA

GGC

= mRNA codes for glycine

CCAGGT

GGU

= mutated DNA

= mRNA still codes for glycine

2. 2. Missense Missense

mutationsmutations

- substitutions that - substitutions that change one amino change one amino acid to another one. acid to another one.

- May have little - May have little effect on the protein effect on the protein or could have a or could have a detrimental effect detrimental effect (such as shape of (such as shape of hemoglobin which hemoglobin which causes sickle cell causes sickle cell anemia).anemia).

3. 3. Nonsense Nonsense mutationsmutations

- a point mutation - a point mutation that codes for a that codes for a STOP codon. STOP codon.

- Causes translation - Causes translation to be terminated to be terminated prematurely and so prematurely and so results in a results in a nonfunctional nonfunctional proteinprotein

May cause little effect on the protein or could be detrimental to the proper function of the protein.

Leads to premature termination of a protein which causes the protein to be nonfunctional.

II. II. Insertions and Insertions and Deletions:Deletions: Are additions or losses of nucleotide Are additions or losses of nucleotide

pairs in a gene.pairs in a gene. Have a disastrous effect on the resulting Have a disastrous effect on the resulting

protein as they may alter the reading protein as they may alter the reading frame of the genetic message.frame of the genetic message.

Called a Called a frameshift mutationframeshift mutation and will and will occur whenever the number of occur whenever the number of nucleotides inserted or deleted is not a nucleotides inserted or deleted is not a multiple of three. Result will be multiple of three. Result will be extensive missense = nonfunctioning extensive missense = nonfunctioning protein.protein.

Deletion or addition of a nucleotide causes the codon sequence to shift. Unless three base pairs are added or deleted, the resulting protein is nonfunctional.

In this case, a G base is deleted from the DNA sequence causing a frameshift mutation.

What Causes Mutations?What Causes Mutations?

Errors during DNA replication which are Errors during DNA replication which are not corrected by DNA polymerase not corrected by DNA polymerase (proofreading) will be used as a template (proofreading) will be used as a template for the next round of replication, resulting for the next round of replication, resulting in a mutation. About one nucleotide per in a mutation. About one nucleotide per 10101010 is altered and passed on. is altered and passed on.

Mutagens in our environment: x-rays, UV Mutagens in our environment: x-rays, UV light, carcinogens (nicotine, pesticides)light, carcinogens (nicotine, pesticides)

Regulation of Regulation of Gene ExpressionGene Expression

Chapter 18 – BIOLOGY AP Chapter 18 – BIOLOGY AP EditionEdition

Regulation of Gene Regulation of Gene Expression:Expression: All cells regulate their gene All cells regulate their gene

expression.expression. Genes get turned on and offGenes get turned on and off Some genes never get turned offSome genes never get turned off Some genes never get turned onSome genes never get turned on

Multicellular eukaryotes develop and Multicellular eukaryotes develop and maintain lots of different cell types. maintain lots of different cell types. Same genome but different genes Same genome but different genes are expressed.are expressed.

Differential Gene Differential Gene Expression:Expression: is the expression of different genes is the expression of different genes

by cells with the same genome.by cells with the same genome. Human body Human body

- lots of different cell types- lots of different cell types- all its cells have the same genomeall its cells have the same genome- however, the subset of genes expressed however, the subset of genes expressed

in each type is unique (nerve cells, liver in each type is unique (nerve cells, liver cells, brain cells, etc.)cells, brain cells, etc.)

Potential control points where gene expression can be turned on, turned off, accelerated or slowed down:

I. Chromatin Modification

II. Transcription

III. mRNA Processing

mRNATranslation

DegradationProtein

Processing and

degradation

Potential control points where gene expression can be turned on, turned off, accelerated or slowed down:I. Chromatin Modification

II. TranscriptionIII. Mechanisms of Post-

Transcriptional Regulation-mRNA Processing-mRNA TranslationDegradation Protein

Processing and degradation

I. Regulation of Chromatin Structure:

Eukaryotic DNA is packed with proteins in an elaborate complex called chromatin.- The structural organization of chromatin helps to regulate gene expression.

- Histone tails protrude outward from the nucleosome making them accessible to various modifying enzymes which catalyze the addition or removal of specific chemical groups.

Histone acetylation promotes a less compact chromatin structure to permit transcription of DNA.

Histone deacetylation promotes a compact chromatin structure so transcription of DNA is not permitted.

DNA Methylation:DNA Methylation:

Addition of methyl groups (-CHAddition of methyl groups (-CH33) to certain ) to certain DNA bases causes gene repression.DNA bases causes gene repression.

Once methylated, genes stay that way Once methylated, genes stay that way through successive cell divisions (DNA through successive cell divisions (DNA replication).replication).

Genomic imprintingGenomic imprinting – a methylation pattern – a methylation pattern in an offspring depends on whether the in an offspring depends on whether the allele was inherited from the mother or the allele was inherited from the mother or the father. Can be used to determine heredity.father. Can be used to determine heredity.

II. Regulation of II. Regulation of Transcription Transcription Initiation:Initiation:

Recall thatRecall that transcription factorstranscription factors areare a a complex ofcomplex of proteins that bind to the proteins that bind to the promoter (TATA box) to assist the promoter (TATA box) to assist the binding of RNA polymerase so that it binding of RNA polymerase so that it can transcribe the gene.can transcribe the gene.

EnhancersEnhancers are DNA sequences located distal to the are DNA sequences located distal to the

promoter of a genepromoter of a gene may be thousands of nucleotides upstream may be thousands of nucleotides upstream

or downstream of a geneor downstream of a gene allow proteins (allow proteins (activators or repressorsactivators or repressors) )

to bind to a control element for the purpose to bind to a control element for the purpose of increasing or decreasing the rate of of increasing or decreasing the rate of expression.expression.

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III. Mechanism of Post-III. Mechanism of Post-Transcriptional Regulation:Transcriptional Regulation:1. 1. Alternative RNA splicingAlternative RNA splicing

different mRNA molecules are produced different mRNA molecules are produced from the same primary transcript, from the same primary transcript, depending on which RNA segments are depending on which RNA segments are treated as exons and which are treated as treated as exons and which are treated as introns.introns.

Example – cells in five different tissues Example – cells in five different tissues splice pre-mRNA for the structural protein, splice pre-mRNA for the structural protein, tropomyosin, into five different mRNAs. tropomyosin, into five different mRNAs. So, each of the five tissues has a different So, each of the five tissues has a different form of tropomyosin.form of tropomyosin.

2. 2. mRNA DegradationmRNA Degradation

Enzymatic shortening of the poly-A tail Enzymatic shortening of the poly-A tail signals other enzymes to remove the 5’ cap signals other enzymes to remove the 5’ cap resulting in rapid degradation of the resulting in rapid degradation of the mRNA.mRNA.

Nucleotide sequences at the 3’ end in an Nucleotide sequences at the 3’ end in an untranslated region affect how long an untranslated region affect how long an mRNA remains intact.mRNA remains intact.

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3. 3. Initiation of TranslationInitiation of Translation Initiation can be blocked by regulatory proteins Initiation can be blocked by regulatory proteins

that bind to an untranslated region at the 5’ end that bind to an untranslated region at the 5’ end of the mRNA, preventing the attachment of of the mRNA, preventing the attachment of ribosomes.ribosomes.

4. 4. Protein Processing and Protein Processing and DegradationDegradation

After translation, the length of time a After translation, the length of time a protein functions in the cell is strictly protein functions in the cell is strictly regulated by means of selective regulated by means of selective degradation.degradation.

Cells mark a protein for destruction Cells mark a protein for destruction by labeling it with a molecule of by labeling it with a molecule of ubiquitinubiquitin, a small protein molecule., a small protein molecule.

Proteasomes recognize the ubiquitin-Proteasomes recognize the ubiquitin-tagged protein and degrade it.tagged protein and degrade it.