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
Post-transcriptional control mRNA processing – polyA tail – 5’ cap – Alternate splicing Remember Spatial and Temporal Seperation RNA silencing
Epigenetics Chromatin Chromosome Epigenetic factors (methyl groups, acetyl groups, phosphate groups) 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 Histone DNA accessible, gene active DNA inaccessible, gene inactive
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.
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?
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.
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.
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: Also called frameshift mutations Substitution Deletion Insertion Translocations
3 types of Substitution Mutations 1.Sense – Creates a new amino acid codon 2.Nonsense – Creates a new stop codon 3.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 Mutated DNA: CGA – TGC – TTC Alanine – Threonine - stop Alanine – Threonine - Lysine This is a substitution What has happened to the protein? Elongated until next stop codon
Substitution Mutations Nonsense mutations Normal DNA: CGA – TGC – TTC Mutated DNA: CGA – TGC – ATC Alanine – Threonine - Lysine Alanine – Threonine - Stop What has happened to the protein? Shorter
Substitution Mutations Missense mutations Normal DNA: CGA – TGC – TTC Mutated DNA: CGA – TGC – GTC Alanine – Threonine - Lysine Alanine – Threonine - Leucine 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. Sickle Shaped Red Blood Cells Normal Red Blood Cells
Frameshift Mutations Change the reading frame of the sequence. Insertions Deletions
This is an insertion mutation, also a type of frameshift mutation. Insertion Mutations Normal DNA: CGA – TGC – ATC Mutated DNA: CGA – TAG – CAT – C Alanine – Threonine – stop Alanine – Isoleucine – Valine What will happen to the amino acids? An adenine was inserted thereby pushing all the other bases over a frame. What has happened to the DNA?
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. Mutated DNA: CGA – TAG – CAT – C Alanine – Leucine - Valine Normal DNA: CGA – TGC – ATC Alanine – Threonine - stop
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.
Mutated DNA: CGA – TCA- TC Alanine – Threonine – stop Alanine – Serine Deletion Mutations Normal DNA: CGA – TGC – ATC 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. Mutated DNA: CGA – TCA- TC Alanine – Threonine – stop Alanine – Serine Normal DNA: CGA – TGC – ATC
Analogy 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
Gene Mutations When does a gene mutation have the greatest affect on an organism? When it occurs in the gamete (egg or sperm) or early in embryonic development (in stem cells or first few days). Four cell Zygote Embryo Egg being fertilized
Age is a Leading Risk Factor for Cancer 10,000 1,000 100 KEY 10 Cancer deaths (per 100,000) Female Male 1 <1 1– 5–9 10 15–19 20 25–34 35– 45–54 55– 75–84 –24 65–74 85+ 4 –14 4464 Age groups in years
From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Radiation is a mutagen Radiation