Changes in DNA that affect genetic information MUTATIONS Changes in DNA that affect genetic information

Mutation change in the genetic material of a cell Germ Cell Mutations Somatic Mutations occur in sex cells and are passed on to offspring take place in body cells

Types of Mutations Gene mutations result from changes in a single gene. Chromosomal Mutations involve changes at chromosome level. Point Mutations – Changes in one or a few nucleotides

Point Mutation: Base Substitution DNA mRNA Amino Acids T A A U methionine isoleucine G C G C G C A T C G U A arginine threonine

Mutations: Substitutions Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons Pro-Glu-Glu-Cys-Gly Amino acids Substitution mutation GGTCACCTCACGCCA ↓ CCAGUGGAGUGCGGU Pro-Arg-Glu-Cys-Gly Substitutions will only affect a single codon. Their effects may not be serious unless they affect an amino acid that is essential for the structure and function of the finished protein molecule.

Substitution: No change Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons Pro-Glu-Glu-Cys-Gly Amino acids Substitution mutation GGTCTTCTCACGCCA ↓ CCAGAAGAGUGCGGU Pro-Glu-Glu-Cys-Gly A mutation may have no effect on the phenotype. Changes in the third base of a codon often have no effect. Example: CTC and CTT both code for Glutamine (Glu).

Substitutions: Disaster Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons Pro-Glu-Glu-Cys-Gly Amino acids Substitution mutation GGTCTCCTCACTCCA ↓ CCAGAAGAGUGAGGU Pro-Glu-Glu-STOP

Point Mutation: Frameshift Mutation Inserting or deleting a nucleotide causes the entire code to “shift.” Insertion THE FAT CAT ATE THE RAT THE FAT CAT XAT ETH ERA T Deletion THE FAT CAT ATE THR AT

Example of Frameshift Mutation DNA mRNA Amino Acids T A A U methionine isoleucine T C G A T A G C U A alanine arginine threonine tyrosine Example of Frameshift Mutation

Mutations: Insertions Addition of a nucleotide causes a frame shift mutation Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons Pro-Glu-Glu-Cys-Gly Amino acids Addition mutation GGTGCTCCTCACGCCA ↓ CCACGAGGAGUGCGGU Pro-Arg-Gly-Val-Arg

Mutations: Deletions A frame shift mutation Normal gene GGTCTCCTCACGCCA ↓ CCAGAGGAGUGCGGU Codons Pro-Glu-Glu-Cys-Gly Amino acids Deletion mutation GGTC/CCTCACGCCA ↓ CCAGGGAGUGCGGU Pro-Gly-Ser-Ala-Val

Gene Mutations Frameshift Mutations – Shifts the reading frame of the genetic message so that the protein may not be able to perform its function. INSERTION THE FAT CAT ATE THE RAT THE FAT HCA TAT ETH ERA T DELETION TEF ATC ATA TET GER AT H H

Chromosomal Mutations Deletion: Part of a chromosome is deleted Duplication: Part of a chromosome is duplicated Inversion: Chromosome twists and inverts the code. Translocation: Genetic information is traded between non-homologous chromosomes.

Types of Chromosome Mutations 1. Deletion occurs when a piece of a chromosome breaks off X X

2. Duplication Occurs when a gene sequence is repeated.

2. Inversion occurs when a piece breaks from a chromosome and reattaches itself to the chromosome in the reverse orientation

Deletion in Chromosome 16

3. Translocation Switch occurs when a broken piece of a chromosome attaches to a non homologous chromosome

Philadelphia Chromosome

Philadelphia Chromosome https://www.youtube.com/watch?v=PNgLK2XuQXc

What Causes Mutations? DNA can become mutated 1. Mutations can be inherited Parent to child 2. Mutations can be acquired Environmental agents (mutagens) Pesticides Tobacco UV radiation Nuclear radiation Mistakes when DNA is copied

Significance of Mutations Most are neutral Eye color Birth marks Some are harmful i.e. Down Syndrome Some are beneficial Sickle Cell Anemia to Malaria Immunity to HIV Evolution - Genetic variability

Objectives: Describe gene regulation in prokaryotes. Explain how most eukaryotic genes are regulated. Relate gene regulation to development in multicellular organisms.

Prokaryotic Gene Regulation Prokaryotes regulate their activities using only those genes necessary for the cell to function. OPERON: Group of structural and regulating genes that function as a single unit.

Prokaryotic Gene Regulation Operons are composed of 4 components: Regulator gene: Codes for a DNA binding protein known as a repressor (prevents RNA polymerase from binding to DNA. Promoter: Region of DNA where RNA polymerase attaches to signal the start of transcription. Operator: Turns transcription on or off by either allowing RNA polymerase to attach to the promoter or not. Structural genes: Group of 3 genes that code for enzyme or proteins.

The Lac Operon When E. Coli (bacteria) is denied glucose and given the milk sugar lactose instead, it immediately begins to make the 3 enzymes needed to metabolize lactose. The 3 structural genes that code for these enzymes are next to each other on the DNA strand and are under the control of a single promoter and a single operator.

The Lac Operon – Lactose Absent When lactose is absent, the regulator gene codes for a repressor that binds to the operator. This prevents RNA polymerase from binding to the promoter. Transcription for the enzymes needed to digest lactose does not take place. (It is unnecessary to waste the energy)

The Lac Operon – Lactose Present When lactose is present, the lactose molecules bind to the repressor, changing the shape of the repressor. The repressor molecule cannot bind to the operator, therefore, RNA polymerase CAN bind to the promoter and transcription does take place. The enzymes needed to digest lactose are created.

Prokaryotic Regulation

Eukaryotic Regulation Unlike prokaryotic cells, a variety of mechanisms regulate gene expression in eukaryotic cells: Chromatin structure Transcriptional control Translational control

Eukaryotic Regulation CHROMATIN STRUCTURE: Chromatin packing is used as a way to keep genes turned off. If genes are not accessible to RNA polymerase, they cannot be transcribed. In the nucleus, highly condensed chromatin is not available for transcription, while more loosely condensed chromatin is available for transcription.

Eukaryotic Regulation TRANSCRIPTION FACTORS: DNA-binding proteins that help initiate transcription. Transcription factors control the expression of genes (determine whether the gene should be shut off or turned on).

Eukaryotic Regulation TRANSLATIONAL CONTROL: Occurs in the cytoplasm and affects when translation begins and how long it continues. Example: Some mRNAs may need further processing before they are translated.

Cell Specialization Eukaryotic cells have copies of all genes, however, different genes are expressed in different types of cells. Example: Muscle cells have a different set of genes that are turned on than nerve cells. Complex gene regulation in eukaryotes is what makes specialization possible.

Professor at Rockefeller RNA Interference Greg Hannon, PhD. Cold Spring Harbor Thomas Tushl, PhD. Professor at Rockefeller

RNA Interference (micro RNA) Cells contain lots of small RNA molecules don’t belong to any of the major groups of RNA (mRNA, tRNA, or rRNA). These small RNA molecules play a powerful role in regulating gene expression by interfering with mRNA.

RNA Interference MicroRNA (miRNA), are small RNA molecules regulate gene expression. miRNA attach to certain mRNA molecules prevent translation from occurring.

RNA Interference Blocking gene expression by means of an miRNA silencing complex is known as RNA interference (RNAi).

The Promise of RNAi Technology RNAi has made it possible to switch genes on and off by inserting double-stranded RNA into cells.

The Promise of RNAi Technology RNAi technology may allow medical scientists to turn off the expression of genes Cancer related diseases may be treated.

Genetic Control of Development Gene expression shapes embryo development. Every cell has the same genes, however, transcription factors and repressors determine which gene is turned on depending on the type of cell it is supposed to differentiate into. The process of cells becoming specialized in structure and function is called differentiation.

Homeotic Genes: “Master Control Genes” Control the identities of body parts in the embryo Regulate organs that develop in specific parts of the body.

Homeobox and Hox Genes Homeotic genes share a very similar 130-base DNA sequence, which was given the name homeobox. Homeobox genes code for transcription factors that activate genes that are expressed in certain regions of the body. They determine factors like the presence of wings or legs.

Homeobox and Hox Genes A group of homeobox genes known as Hox genes are located side by side in a single cluster. Hox genes determine the identities of each segment of an animal’s body. Hox genes tell the cells of the body how to differentiate as the body grows.

Homeobox and Hox Genes The colored areas on the fly show the approximate body areas affected by genes of the corresponding colors. A mutation in one of these genes can completely change the organs that develop in specific parts of the body. Clusters of Hox genes exist in the DNA of other animals, including humans.

Environmental Influences Environmental factors like temperature, salinity, and nutrient availability can influence gene expression. Example: The lac operon in E. coli Metamorphosis is another example of how organisms can modify gene expression in response to their environment. Example: Unfavorable conditions may force a frog to undergo metamorphosis faster than usual.