BIOL 4003 Week 11 Lectures
BIOL 4003 Week 11 Lectures 4003
U of M
Popular in Principles of Genetics
verified elite notetaker
Popular in Biology
verified elite notetaker
This 9 page Class Notes was uploaded by Rachel Heuer on Monday April 11, 2016. The Class Notes belongs to 4003 at University of Minnesota taught by Robert Brooker in Spring 2016. Since its upload, it has received 7 views. For similar materials see Principles of Genetics in Biology at University of Minnesota.
Reviews for BIOL 4003 Week 11 Lectures
Report this Material
What is Karma?
Karma is the currency of StudySoup.
You can buy or earn more Karma at anytime and redeem it for class notes, study guides, flashcards, and more!
Date Created: 04/11/16
Chapter 18: Mutation: A heritable change in genetic material (must be passed from cell to cell and parent to offspring) o Mutation provides allelic variations o Variation within a species cause environmental adaptations o New mutations are more likely to be harmful than beneficial and often cause diseases Organisms have a way to repair damaged DNA Mutations can be divided into three types: o Chromosomal (change in chromosome structure) o Genome mutations (change in chromosome number) o Gene mutations (small change in DNA that affects a single gene) Point mutation: causes change in a single base pair Can involve base substitution Transition: turning a pyrimidine (C, T) into another pyrimidine (or purine (A, G) to another purine) Transversion: changing a pyrimidine to a purine (or vice versa) Transitions are more common than transversions o Because it does not create as large of a distortion in the DNA strand and is less likely to be noticed by DNA polymerase Could be an addition or deletion of short sequences of DNA Causes frame shift in coding sequence o Missense: changes one codon o Silent: No change in codon sequence o Nonsense: Early termination of translation (stop) o Frameshift: all or most of the amino acids downstream from the insertion or deletion will be different Mutations outside of coding sequence can still affect phenotype o Mutations in the core promoter can change levels of gene expression Up mutations increase expression Down mutations decrease expression o Mutations in regulatory elements, UTRs and splice sites can also change levels of gene expression o Suppressor: A separate mutation can restore a loss of function mutation Intragenic: separate mutation is within the same gene to restore function Intergenic: separate mutation is outside of gene and compensates for the defect in the first gene Mutations can occur in both germline or somatic cells o Germline cells: cells that give rise to gametes such as eggs and sperm Germline mutations: those that occur directly in a sperm or egg cell, or in one of their precursor cells Half of offspring pass on germline mutation o Somatic cells: all other cells Somatic mutations: those that occur directly in a body cell, or in one of its precursor cells No offspring pass on a somatic mutation Genetic mosaic: individual who has somatic regions that are genotypically different from each other Mutations occur randomly/spontaneously or because of environmental conditions? o Natural selection creates better adapted organisms o Jean Baptiste Lamarck Physiological Adaptation Proposed that physiological events (use and disuse) determine whether traits are passed along to offspring o Alternative possibility Random Mutations Genetic variation occurs by chance Natural selection results in betteradapted organisms This is CORRECT Spontaneous Mutations o Result from abnormalities in cellular/biological processes Such as DNA replication Caused by something within the cell o Can arise by three types of chemical changes Depurination – most common A purine is removed (A or G) o Missing purine site is apurinic site DNA no longer knows which matching base is correct (when apurinic site is on template strand) o 75% chance of getting a mutation, 25% chance of inserting correct base Deamination Involves removing an amino group from the cytosine base o Other bases are not readily deaminated o Changes Cytosine to uracil (or thymine) o DNA repair enzymes can recognize uracil as an inappropriate base in DNA and remove it However, if the repair system fails, a CG to A T mutation will result during subsequent rounds of DNA replication Methylated cytosine bases are hot spots for mutation because repair enzyme cannot determine which of the two bases on the two DNA strands is the incorrect base Tautomeric Shift Temporary change in base structure o The common, stable form of thymine and guanine is the keto form At low rate G and T can convert to enol form o The common, stable form of adenine and cytosine is the amino form At low rates C and A can convert to imino form These rare forms promote AC and GT base pairs For a tautomeric shift to cause a mutation, it must occur immediately prior to DNA replication Can cause incorrect base pairing 1 shift creates 25% mutation rate o Oxidative stress can lead to DNA damage Aerobic organisms produce Reactive Oxygen Species (ROS) Such as hydrogen peroxide, superoxide and hydroxyl radicals Body tries to block build up of ROS Builds enzymes that break down ROSs ROS overaccumulation can lead to Oxidative DNA Damage Chemically alters base pairing o Many human genetic diseases are caused by trinucleotide repeat expansions (TNRE) Certain regions of the chromosome contain trinucleotide sequences repeated in tandem In normal individuals, these sequences are transmitted from parent to offspring without mutation However, in persons with TNRE disorders, the length of a trinucleotide repeat has increased above a certain critical size o Disease symptoms occur Above a certain size, TNRE causes changes in gene function Can form base pairs and changes in DNA structure hair pin forms, which pushes DNA polymerase off of template strand and causes it to replicate the same region twice Continually gets expanded Induced mutations o Caused by something outside of the cell Such environmental agents o Mutagens: Agents that alter DNA structure and cause mutations Such as chemical or physical agents Often involved in development of cancer Can cause gene mutations that can have harmful effects in future generations A huge array of things can cause mutations Can be either chemical or physical mutagens o Chemical mutagens come into three main types: Base modifiers Alkylate bases to disrupt pairing Covalently modify base structure Intercalating agents: Directly interfere with replication process Base analogues: Incorporate into DNA during replication and disrupt structure Can cause Tautomerization at high rates o Physical Mutagens Radiation can damage DNA Either by causing chemical changes in the bases or breaking DNA strands Ionizing radiation: more powerful X rays and gamma rays Short wavelengths, high energy Penetrate deeply into biological molecules Can create chemically reactive molecules termed free radicals in our body o Can then cause base deletions, nicks in DNA strands, oxidized bases, crosslinking, chromosomal breaks Nonionizing Includes UV light Less energy Does not penetrate as deeply into biological molecules Creates crosslinked thymine dimers o Thymine dimers cause mutations when strand is replicated o Mutation Rate: Likelihood that a gene will be altered by a new mutation. Typically expressed as # of new mutations in a gene per cell generation In the range of 10 10 per generation o Humans add 100200 new mutations per generation Mutation rate is not constant for a given gene Changes due to presence of mutagens Varies between species and cell type o Testing methods can determine if an agent is a mutagen Ames Test Uses a strain of salmonella that cannot synthesize histidine o It has a point mutation in a gene involved in histidine biosynthesis A second mutation may occur and restore ability to synthesize histidine nd Ames test moniters rate at which that 2 mutation occurs With added mutagens, you will get lots of expected growth on the plate Mutation has to be heritable and not fixed DNA can repair mutations since most mutations are deleterious o Vital to survival of organisms o DNA repair is a multistep process Irregularity in DNA structure is detected Abnormal DNA is removed Normal DNA is synthesized o Know the steps to nucleotide excision repair system and mismatch repair system o Nucleotide excision repair (NER) removes damaged DNA segments Recognizes dramatic helix distortions Such as dimers, chemically modified bases, missing bases and crosslinks NER is found in all eukaryotes and prokaryotes. o Requires 4 key proteins in E. coli UvrA, UvrB, UvrC, UvrD Recognize and remove short segments of damaged DNA DNA polymerase and ligase finish the repair job Figure 18.18 UvrA/UvrB tracks along the strand in search of damaged DNA After damaged DNA is detected, UvrA is released and UvrC binds UvrC makes cuts on both sides of the damaged DNA UvrD (helicase) removes the damaged region o UvrB and UvrC are released DNA polymerase fills in the gap and DNA ligase seals the region o Mismatch repair system detects and corrects a base pair mismatch Used when AT/GC rule is not followed and 3’ to 5’ DNA polymerase proofreading does not catch the mistake Relies on idea of getting rid of mismatch in newly made daughter strand (not in the parental methylated strand) MutH decides which strand is template and which is daughter (by looking for methylation) MutS (and L) find a mismatch and bring MutH into the complex; MutL communicates between MutH and MutS tells MutS which strand is the correct one o Tells which strand to cut MutH cuts strand and an exonuclease eats away proper stand until past the mismatch DNA polymerase comes back in and resynthesizes the strand Chapter 19: Genetic recombination involves chromosomes breaking and rejoining to form new combinations o 3 types Homologous recombination (meiosis) Occurs between homologous (identical) DNA segments Segments break and rejoin to form new combinations Site Specific recombination Occurs when nonhomologous DNA segments are recombined at specific sites We wont talk about Transposition Occurs when small segments of DNA called transposons move to multiple positions within the hosts chromosomal DNA Homologous Recombination o Crossing over occurs frequently during meiosis I and occasionally during mitosis o Involves alignment of a pair of homologous chromosomes, followed by breakage at analogous locations and exchange of corresponding segments o Crossing over that occurs between sister chromatids is called sister chromatid exchange (SCE) Sister chromatids are genetically identical to each other Therefore, SCE does not produce a new combination of alleles NOT a form of recombination o Homologous chromosomes crossover creates genetic recombination Homologous chromosomes can carry different alleles of the same gene o Holliday Model for Homologous Recombination Chromosomes line up (Crossover strands are in the same direction (5 3)) Crossover strands are nicked DNA to the left of nick, crosses to other strand and links to the the right side of the nick Creates the holliday junction Strands migrate across to new strand Heteroduplex region (with some base pair mismatches) Crisscrossed strands are cut and rejoined to original strand Non recombinant Or can cut in a different way, creating recombinants Resolution phase determines whether recombinant crossover occurs Two nicks in the same exact spot is rare More realistically, a DNA helix probably incurs a single nick or a double strand break (most common) o Complete break in one whole chromatid o Broken strand invades other chromatid o Creates a Dloop bulge o Dloop is resolved by being cut and combined to the new DNA o Can get nonrecombinants or recombinants depending on how strands are cut Homologous recombination is found in all species Different proteins in cells carry out different functions in homologous recombination o Gene conversion: Genetic recombination can cause two different alleles to become identical alleles Can occur through mismatch DNA repair DNA gap repair synthesis During branch migration mismatches occur Can be repaired to create 4 different sequences (after the holliday model) Gap repair synthesis can cause gene conversion in double strand break model One allele is lost, DNA from other gene is copied and allele is same in both homologous chromosomes Figure 19.7 Transposition: Integration of small segments of DNA into chromosome o Can occur in many locations within the genome o Small, mobile DNA segments are referred to as transposable elements (TEs) o Two general types of transposition pathways have been identified Simple (conservative transposition) DNA segment (transposon) cut out and pasted into a new location of DNA Called “cut and paste” Found in prokaryotes and eukaryotes Retrotransposition transposon is transcribed into RNA and back to DNA o Then inserted into the chromosomal DNA o Only in eukaryotes o Transposon does not physically move, but is copied o TE moves via and RNA intermediate o These are termed retroelements, retrotransposons, or retroposons o Transposable elements have characteristic DNA sequences Figure 19.11 DNA sequences within transposable elements are organized in several different ways Has direct repeats (found within host DNA), inverted repeats (identical sequences that run opposite directions around transposase gene), transposon Can have additional genes for selective advantages (antibiotic resistance) o Retrotransposons Have Long terminal repeats Look like viruses Organization of sequences is quite variable Categorized based on evolutionary history to retroviruses With LTR (long terminal repeats) is much like retrovirus Without LTR (long terminal repeats) very little in common with retroviruses o May contain a gene encoding a protein with both reverse transcriptase and endonuclease function Retroviruses are RNA viruses that make a DNA copy that integrates into the host’s genome Like their viral counterparts, they encode virally related proteins that are needed for the transposition process o Transposase catalyzes the excision and insertion of transposable elements Catalyzes the removal of a TE and its reinsertion at another location Recognizes inverted repeats at the ends of a TE and brings them closer together One transposase binds to each inverted repeat Figure 19.12 Creates a staggered cut DNA polymerase (gap repair) and DNA ligase fills in the gaps This creates Direct repeats Retrotransposons also create Direct repeats this way o Transposon is proliferated because transposition can occur over the replication fork during DNA replication Figure 19.13 o Retroelements: use reverse transcriptase and integrase Use an RNA intermediate in their transposition mechanism Figure 19.14 Requires two enzymes: Reverse transcriptase and integrase Can make many copies Can proliferate very fast because one transposable element RNA can be reinserted multiple times Transcriptase makes RNA copy from DNA TE Reverse transcriptase turns RNA into DNA Integrase reinserts DNA into chromosome AT rich region is found and made into RNA Endonuclease finds another AT rich region and cuts it Separating strands Short polyA tail on RNA binds to this broken strand Reverse transcriptase makes DNA complementary attached to the RNA Targetsite primed reverse transcription Second cut is made, new DNA regions must be made and filled in (RNA is lost) TE influences on mutation and evolution o Can have lots of effects o Large part of eukaryote genome is from TEs 45% of human DNA is transposable DNA o Simple organisms have less abundant TEs o TEs typically cause negative effects Can have a benefit but normally mess things up
Are you sure you want to buy this material for
You're already Subscribed!
Looks like you've already subscribed to StudySoup, you won't need to purchase another subscription to get this material. To access this material simply click 'View Full Document'