Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Genomics of sensory systems - University of Maryland
Document related concepts
Human genome wikipedia , lookup
Protein moonlighting wikipedia , lookup
Point mutation wikipedia , lookup
History of genetic engineering wikipedia , lookup
Gene nomenclature wikipedia , lookup
Gene expression programming wikipedia , lookup
X-inactivation wikipedia , lookup
Segmental Duplication on the Human Y Chromosome wikipedia , lookup
Epigenetics of human development wikipedia , lookup
Therapeutic gene modulation wikipedia , lookup
Minimal genome wikipedia , lookup
Gene therapy of the human retina wikipedia , lookup
Polycomb Group Proteins and Cancer wikipedia , lookup
Gene expression profiling wikipedia , lookup
Vectors in gene therapy wikipedia , lookup
Microevolution wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
Genome editing wikipedia , lookup
Genome (book) wikipedia , lookup
Designer baby wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Transcript
A return to our senses 9/28/09 1. Gene duplications by mismatched recombination If chromosomes misalign, recombination leads to gain of gene on one chromosome and loss of gene on the other. Tandem arrays of genes 2. Insertion of retrotranposed gene Fugu fish scaffold 830 Rh1 Human chr 3 Human chr Z Fugu Rh gene has been inserted into chromosome 3. Gene duplication as part of whole genome duplication Meiosis 2n chromosomes Gametes n 3. Normal fertilization Sperm + Egg Zygote 2n chromosomes 3. Failure of meiosis Nondisjunction Gamete, 2n chromosomes Genome duplication + Zygote, 4n Evidence that genome duplication occurs Genome size varies between organisms Prokaryotes E coli Human 0.6 Mb 4.7 Mb 3400 Mb Chromosome Drosophila Human Chicken Lamprey 500 genes 6000 genes 25,000 genes # varies (2n) 8 46 78 168 Other evidence If duplicate whole chromosome, will see many genes duplicated See similar trees for all genes See similar gene order on two duplicated chromosomes G protein subunit tree Chromosome arrangement Tandem duplication and then chromosomal duplication Synteny “the preserved order of genes on chromosomes of related species, as a result of descent from a common ancestor” Chromosomes can break and stick back together AnoleR ChickR AtigrinumR LWS GaustralisLWS HumanG HumanR AnoleRH2 ChickG TilapiaG1 RH2 ZebrafishG1 ZebrafishG2 GaustralisRhB AnoleRH ChickRh HumanRh RH1 XlaevisRH ZebrafishRh GaustralisRHA AnoleS2 SWS2 ChickB ZebrafishB GaustralisSWS2 AnoleS1 ChickUV SWS1 HumanB GaustralisS1 ZebrafishUV Chromosomes containing opsin genes came from duplicates SWS1 = OPN1SW LWS = OPN1LW RH1 = RHO Chromosomal duplication and then tandem duplication Vertebrate genome duplications Human 92 71 Cow 41 Mouse Rat 276 Reptiles 310 Birds 360 2x Amphibians Tilapia 2x 2x 120 200 Fugu 250 Zebrafish 528 Cartilagenous fish 564 600 500 400 Lamprey Agnatha 300 Time (Myr) Bony fish 200 100 0 Kumar and Hedges 1998 Gene duplicate divergence times Genome duplication in fishes 350 Mya Meyer and van der Peer 2005 G protein pathway in rods Phototransduction proteins Protein Rods Opsin RH1: Rho Transducin TrGNAT1 TrGNB1 Tr: GNGT1 PDE: PDE6A PDE: PDE6B PDE: PDE6G CNGA1 CNGB1 GRK-1 Phosphodiesterase cGMP gated ion channel G protein coupled receptor kinase Arrestin SAG Recoverin RCV1 Phosducin PDC PD-R GUCYD2 + GUCYF2 GC-R Guanylate cyclase Cones Phototransduction proteins Protein Rods Cones Opsin RH1: Rho Transducin TrGNAT1 TrGNB1 Tr: GNGT1 PDE: PDE6A PDE: PDE6B PDE: PDE6G CNGA1 CNGB1 GRK-1 SWS1: OPN1S SWS2 RH2 M/LWS: OPN1M, OPN1L TcGNAT2 TcGNB3 Tc: GNGT2 PDE’: PDE6C PDE’: PDE6H Phosphodiesterase cGMP gated ion channel G protein coupled receptor kinase Arrestin CNGA3 CNGB3 GRK-7 SAG ARR3 Recoverin RCV1 RCV1 s26 (frog) Phosducin PDC PD-R GUCYD2 + GUCYF2 GC-R Guanylate cyclase PD-C (medaka) GC-C (medaka) Sources of gen(om)e evolution: Nucleotide sequence - coding sequence Regulatory sequence - alter gene expression Gene splicing - alter exon combos Gene duplication Segmental duplication Chromosomal duplication Genome duplication How fast do these things happen - DNA mutation? Each nucleotide will mutate (change) every 100-500 MY Entire genome will change in 500 MY Some nucleotides change a lot - others not very much Depends on selection substitutions/site * 109 Li and Graur 2003 Codons Non-Syn Synonymous How fast do these things happen - genome duplication? Genome duplications have occurred 3-4 times in vertebrate history (1 per 100 MY) Get 3-4 copies of each gene How fast do these things happen - gene duplication? Any given gene will duplicate on average every 100 MY Get 3-4 copies of every gene But most of duplicates will go nonfunctional in about 4 MY How fast do these things happen? - Summary Genome duplications have occurred 3-4 times in vertebrate history (1 per 100 MY) Any given gene will duplicate on average every 100 MY Each nucleotide will mutate (change) every 100-500 MY Goals for rest of semester How do sensory cells function? Structural basis Molecular basis How has gen(om)e evolution shaped sensory systems? Why are animals the way they are? Sensory organs R e c e p t o r s What are senses good for? Convert outside stimuli to neural signal Stimulus causes a conformational change in a receptor molecule This causes change in membrane potential through ion channel This sends neural signal Sensory transduction Ionotropic Receptor change directly alters membrane potential Receptor IS the ion channel Iono - ions -tropic affecting Sensory transduction Ionotropic Ligand gated ion channel Sensory transduction Metabotropic Receptor change activates G protein which activates effector molecule which opens / closes ion channel Indirect link to ion channel Metabo- change -tropic affecting Can be both ionotropic and metabotropic receptors for same ligand, e.g. Glutamate receptors Role of membrane Most sensory cells rely on receptor Integral to membrane Cells contain special sensory membrane More membrane = more receptors More sensitivity Ways to maximize membrane #1 Microvilli Evagination - out pocketing Strengthen with actin fibers - can be tightly packed Kinds of microvillar sensory cells Hair cells Invertebrate photoreceptors Ways to maximize membrane #2 Cilium Evagination Based on tubulin Typically 9 double microtubules surround 2 central microtubules 9+2 Cilia Olfactory receptors Photoreceptors Membrane organization Sensory membrane is specialized Region of cell where receptor and other proteins transduce signals Helpful to localize proteins Attach to scaffolding proteins Tether to membrane Drosophila photoreceptor 50,000 microvilli INAD-scaffolding protein 5 protein binding domains Interconnect transduction proteins Figure 2.5 Vertebrate rods - integral vs tethered proteins Membrane renewal Signal transduction is high stress Need to fix damage Replace sensory membrane Vertebrate photoreceptors Invert photoreceptor membrane totally disintegrates Replace entire cell Olfactory and taste cells Phagocytosis of sensory membrane Olfactory cell half life - 90 days Regrow from basal stem cells Olfactory cell half life - 90 days Replace each of the 100-1000 cells. Have to find right connection when replaced. Taste buds Half life is approximately 10 days Need to make correct neural connections How does this happen???? External specializations Extra structure to enhance function Protection Decrease sensitivity Increase sensitivity Protection Pressure detection by palicinian corpuscle Layers decrease sensitivity Most sensitive to pressure Statocysts Cells of equilibrium Hollow sphere with 400 mechanoreceptors in bristles Statolith - sand grain mass As lobster moves, statolith stimulates different cells and determines orientation Scallop eyes Scallop Both cilliary and microvillar photoreceptors in same structure Scallop Differ in neural response to light Microvillar - depolarize Ciliary - hyperpolarize See Fig 2.11 in Fain Differences in stimulus response Activation of receptor triggers ion channel Channel OPEN or CLOSE Differences in stimulus response Activation of receptor changes membrane potential DEPOLARIZE HYPERPOLARIZE Differences in stimulus output Sensory neurons can be PRIMARY Propagate action potentials down axons SECONDARY Synaptic input to 2nd cell which generates action pot Increasing sensitivity Lots of membrane Transduction pathway amplifies signal X 10 -1000 No increase in noise Reduce spontaneous receptor activation Adaptation Response to constant stimulus decreases with exposure to steady state
