Mutations: are changes to the genetic information of a cell are responsible for the huge diversity among living things are the ultimate source of new genes

Point Mutations: Changes in a single base pair of a gene can lead to the production of an abnormal protein: Wild-type Hemoglobin Mutant Hemoglobin 3’-CTT-5’ 3’-CAT-5’ 5’-GAA-3’ 5’-GTA-3’ 5’-GAA-3’ 5’-GUA-3’ = Normal hemoglobin = Sickle-cell hemoglobin DNA DNA mRNA mRNA

Types of Point Mutations: I. Base-pair substitutions – one base pair replaced by another pair 1. Silent mutations – due to redundancy of the genetic code, there is no effect on the encoded protein CCG GGC = WT DNA GGC = mRNA codes for glycine CCA GGT = mutated DNA GGU = mRNA still codes for glycine

2. Missense mutations - substitutions that change one amino acid to another one. - May have little effect on the protein or could have a detrimental effect (such as shape of hemoglobin which causes sickle cell anemia). 3. Nonsense mutations - a point mutation that codes for a STOP codon. - Causes translation to be terminated prematurely and so results in a nonfunctional protein

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. Insertions and Deletions: Are additions or losses of nucleotide pairs in a gene. Have a disastrous effect on the resulting protein as they may alter the reading frame of the genetic message. Called a frameshift mutation and will occur whenever the number of nucleotides inserted or deleted is not a multiple of three. Result will be extensive missense = nonfunctioning protein.

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

What Causes Mutations? Errors during DNA replication which are not corrected by DNA polymerase (proofreading) will be used as a template for the next round of replication, resulting in a mutation. About one nucleotide per 1010 is altered and passed on. Mutagens in our environment: x-rays, UV light, carcinogens (nicotine, pesticides)

Regulation of Gene Expression Chapter 18 – BIOLOGY AP Edition

Regulation of Gene Expression: All cells regulate their gene expression. Genes get turned on and off Some genes never get turned off Some genes never get turned on Multicellular eukaryotes develop and maintain lots of different cell types. Same genome but different genes are expressed. Regulate = turning genes on and off in response to signals from their internal and external environments. Multicellular organisms are made up of many different cell types, each with a distinct role. To perform its role, each cell type must maintain a specific program of gene expression in which certain genes are expressed and others are not.

Differential Gene Expression: is the expression of different genes by cells with the same genome. Human body - lots of different cell types all its cells have the same genome however, the subset of genes expressed in each type is unique (nerve cells, liver cells, brain cells, etc.)

I. Chromatin Modification II. Transcription III. mRNA Processing Potential control points where gene expression can be turned on, turned off, accelerated or slowed down: I. Chromatin Modification II. Transcription III. mRNA Processing mRNA Translation Degradation Protein Processing and degradation In all organisms (prokaryotes and eukaryotes), a common control point for gene expression is at transcription; regulation at this stage is often from signals outside the cell such as hormones or other signaling molecules. For that reason, the term gene expression is often equated with transcription for both bacteria and eukaryotes. Eukaryotes, however, are a more complicated cell structure and therefore offer many opportunities for regulating gene expression at many additional stages. The remainder of this discussion is regarding eukaryotes.

I. Chromatin Modification II. Transcription Potential control points where gene expression can be turned on, turned off, accelerated or slowed down: I. Chromatin Modification II. Transcription III. Mechanisms of Post-Transcriptional Regulation -mRNA Processing -mRNA Translation Degradation 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: Addition of methyl groups (-CH3) to certain DNA bases causes gene repression. Once methylated, genes stay that way through successive cell divisions (DNA replication). Genomic imprinting – a methylation pattern in an offspring depends on whether the allele was inherited from the mother or the father. Can be used to determine heredity.

II. Regulation of Transcription Initiation: Recall that transcription factors are a complex of proteins that bind to the promoter (TATA box) to assist the binding of RNA polymerase so that it can transcribe the gene. Enhancers are DNA sequences located distal to the promoter of a gene may be thousands of nucleotides upstream or downstream of a gene allow proteins (activators or repressors) to bind to a control element for the purpose of increasing or decreasing the rate of expression.

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III. Mechanism of Post-Transcriptional Regulation: 1. Alternative RNA splicing different mRNA molecules are produced from the same primary transcript, depending on which RNA segments are treated as exons and which are treated as introns. Example – cells in five different tissues splice pre-mRNA for the structural protein, tropomyosin, into five different mRNAs. So, each of the five tissues has a different form of tropomyosin.

2. mRNA Degradation Enzymatic shortening of the poly-A tail signals other enzymes to remove the 5’ cap resulting in rapid degradation of the mRNA. Nucleotide sequences at the 3’ end in an untranslated region affect how long an mRNA remains intact. http://highered.mcgraw-hill.com/sites/0072437316/student_view0/chapter18/animations.html#

3. Initiation of Translation Initiation can be blocked by regulatory proteins that bind to an untranslated region at the 5’ end of the mRNA, preventing the attachment of ribosomes.

4. Protein Processing and Degradation After translation, the length of time a protein functions in the cell is strictly regulated by means of selective degradation. Cells mark a protein for destruction by labeling it with a molecule of ubiquitin, a small protein molecule. Proteasomes recognize the ubiquitin-tagged protein and degrade it.