Gene Expression Eukaryotic versus Prokaryotic Structure dictates function

Prokaryotic transcription is simpler DNA exists in one chromosome Less non-coding sequence RNA polymerase binds the promoter directly Genes are clustered into functional groups called operons

Lac Operon

Eukaryotic transcription is far more complex Transcription factors are required to articulate between RNA polymerase and promoter Enhancers and Silencers (DNA sequences that affect gene expression) “Positionally free” Genes include introns Genes can be methylated on Cs More methylation less expression Less methylation more expression

Eukaryotic Transcription

Post-transcriptional control mRNA processing polyA tail 5’ cap Alternate splicing Remember Spatial and Temporal Seperation RNA silencing

Epigenetics Chromatin Epigenetic factors (methyl groups, acetyl groups, phosphate groups) Chromosome DNA methylation Methyl group can tag DNA and activate or repress genes. Histone tails Methyl group Histone modification The binding of epigenetic factors to histone “tails” alters the extent to which DNA is wrapped around histones and the accessibility of genes in the DNA. DNA Gene Histones are proteins around which DNA can wind for compaction and gene regulation DNA accessible, gene active Histone DNA inaccessible, gene inactive

Video

Wrap up Was that video happening in a eukaryotic cell or prokaryotic cell? Make a T chart of structural differences between prokaryotic and eukaryotic cells that effect their gene expression Short sheets with review questions

What is a gene mutation? Mutations are changes in genetic material – changes in DNA code – thus a change in a gene(s) In gene mutations, the DNA code will have a base (or more) missing, added, or exchanged in a codon. General introduction (definition) about mutation

How common are mutations? Humans:Mutations occurs at a frequency of about 1 in every 1 billion base pairs Everybody has about 6 mutations in each cell in their body! What do you think the rate of mutation in bacterial cells are? A fun fact about how common mutations are. Explain that everyone has mutations, although they are not always seen because the mutation may have occurred in a section of DNA that doesn’t make a protein.

If I have that many mutations, why don’t I look weird? Mutations are not always seen. The affected gene may still function. Mutations may be harmful. Mutations may be beneficial. Mutations may have no effect on the organism. Explain that everyone has mutations, although they are not always seen because the mutation may have occurred in a section of DNA that doesn’t make a protein or the mutation may cause a cell to die (while not affecting the function of the organ).

How do mutations affect a population? Mutations are a major source of genetic variation in a population increasing biodiversity. Some variations may help them to survive better. Clip Art

How are mutations inherited? Only mutations in gametes (egg & sperm) are passed onto offspring. Mutations in body cells only affect the organism in which they occur and are not passed onto offspring.

Types of Gene Mutations There are 4 types: Substitution Also called frameshift mutations Deletion Insertion Translocations General information about the three most common types of mutations to transition into the examples

3 types of Substitution Mutations Sense Creates a new amino acid codon Nonsense Creates a new stop codon Missense Creates a change in 1 amino acid 4. Silent Creates no change in amino acid sequence

Substitution Mutations Sense mutations Normal DNA: CGA – TGC – ATC Alanine – Threonine - stop Mutated DNA: CGA – TGC – TTC Alanine – Threonine - Lysine Ask students if they can figure out what is happening in this mutation. Answer is on the next slide. What has happened to the protein? Elongated until next stop codon This is a substitution

Substitution Mutations Nonsense mutations Normal DNA: CGA – TGC – TTC Alanine – Threonine - Lysine Mutated DNA: CGA – TGC – ATC Alanine – Threonine - Stop Ask students if they can figure out what is happening in this mutation. Answer is on the next slide. What has happened to the protein? Shorter

Substitution Mutations Missense mutations Normal DNA: CGA – TGC – TTC Alanine – Threonine - Lysine Mutated DNA: CGA – TGC – GTC Alanine – Threonine - Leucine Ask students if they can figure out what is happening in this mutation. Answer is on the next slide. What has happened to the protein? Changed by one amino acid same length

Gene Mutations An example of a substitution mutation is sickle cell anemia. Only one amino acid changes in the hemoglobin. The hemoglobin still functions but it folds differently changing the shape of the rbc. Normal Red Blood Cells The hemoglobin ends up with a differently charged amino acid that caused the RBC to stick to itself. This is the sickle part. This affects the way hemoglobin can carry oxygen. Sickle Shaped Red Blood Cells

Frameshift Mutations Change the reading frame of the sequence. Insertions Deletions

Insertion Mutations What has happened to the DNA? Normal DNA: CGA – TGC – ATC Alanine – Threonine – stop Mutated DNA: CGA – TAG – CAT – C Alanine – Isoleucine – Valine Ask students if they can figure out what is happening in this mutation. Answer is on the next slide. What has happened to the DNA? What will happen to the amino acids? This is an insertion mutation, also a type of frameshift mutation. An adenine was inserted thereby pushing all the other bases over a frame.

Insertion Mutations This is an insertion mutation. A nitrogen base is inserted/added to the sequence. It causes the triplet “frames” to shift. It always affects the amino acids and, consequently, the protein. Ask students if they can figure out what is happening in this mutation. Answer is on the next slide. Normal DNA: CGA – TGC – ATC Alanine – Threonine - stop Mutated DNA: CGA – TAG – CAT – C Alanine – Leucine - Valine

Analogy Insertion The cat ate the rat. The cca tat eth era t. Inserting the c causes a FRAMESHIFT THE SENTENCE NO LONGER MAKES SENSE!! Insertions may have huge effects.

Deletion Mutations Normal DNA: CGA – TGC – ATC Alanine – Threonine – stop Mutated DNA: CGA – TCA- TC Alanine – Serine Ask students if they can figure out what is happening in this mutation. Answer is on the next slide. This is called a deletion mutation, also a type of frameshift mutation.

Deletion Mutations This is a deletion mutation. A nitrogen base is deleted/removed from the sequence. It causes the triplet “frames” to shift. It always affects the amino acids and, consequently, the protein. Ask students if they can figure out what is happening in this mutation. Answer is on the next slide. Normal DNA: CGA – TGC – ATC Alanine – Threonine – stop Mutated DNA: CGA – TCA- TC Alanine – Serine

Analogy Thc ata tet her at FRAMESHIFT DELETION The cat ate the rat. Thc ata tet her at FRAMESHIFT The sentence no longer makes sense!! Deletions can have huge effects.

Don’t put an oncogene in front of a promoter: Translocations

Translocations

Gene Mutations When does a gene mutation have the greatest affect on an organism? Egg being fertilized When it occurs in the gamete (egg or sperm) or early in embryonic development (in stem cells or first few days). Stem cells have the remarkable potential to develop into many different cell types in the body. Serving as a sort of repair system for the body, they can theoretically divide without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential to either remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell. Four cell Zygote Embryo

Age is a Leading Risk Factor for Cancer 10,000 1,000 100 Cancer deaths (per 100,000) KEY 10 Male Female 1 <1 4 1– 5–9 –14 –24 44 64 85+ 15–19 25–34 45–54 65–74 75–84 10 20 35– 55– Age groups in years

Radiation Radiation is a mutagen From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.