Download Chromosomal theory of inheritance

1/24/13 Gene*cs Principles 23 January 2013 Rebecca Lowdon Outline •  Inheritance / Transmission gene*cs –  Mendel & classical gene*cs •  Meiosis: mechanism that unites inheritance and chromosomes –  Chromosomal theory of inheritance, Walter SuLon •  Muta*on –  Morgan and Muller •  Characteris*cs of Phenotypes and Non-­‐Mendelian Inheritance –  Non-­‐Mendelian inheritance –  Gene*cs vs epigene*cs •  Popula*on gene*cs: study of gene*c varia*on in popula*ons 1 1/24/13 Outline •  Inheritance / Transmission gene*cs –  Mendel & classical gene*cs •  Meiosis: mechanism that unites inheritance and chromosomes –  Chromosomal theory of inheritance, Walter SuLon •  Muta*on –  Morgan and Muller •  Characteris*cs of Phenotypes and Non-­‐Mendelian Inheritance –  Non-­‐Mendelian inheritance –  Gene*cs vs epigene*cs •  Popula*on gene*cs: study of gene*c varia*on in popula*ons Mendel’s Aims 1.  Characterize hybrid phenotypes. 2.  Determine pedigrees for hybrids. 3.  Quan*fy phenotype ra*os. 2 1/24/13 Mendel •  Deduced paLerns of inheritance from breeding experiments. –  Dominance: an allele masks expression of the second allele for a trait/at a locus. –  Recessivity: an allele/phenotype that is only expressed in the homozygote. •  Gene: the unit of heredity. •  Homozygote: an individual has two of the same alleles for a locus. •  Heterozygote (hybrid): an individual has two different alleles at a locus. Mendel’s Principles of Inheritance •  Law of Segrega8on: For autosomal traits, there is a 50% chance of passing on either maternal/paternal allele. •  Law of Independent Assortment: Genes for different traits are inherited independently. 3 1/24/13 Mendelian Probabili*es •  PunneL Square incorporates independent assortment and segrega*on. •  Fisher’s issue with Mendel’s results? P
Pp
Pp
–  They were too close to expecta*on •  Illustra*on of Mendel’s results –  Coin-­‐flip simula*on, repea*ng the experiment 1000 *mes. •  Ques*on #4: 1.  Unconscious bias 2.  Exclusion due to assumed experimental error 3.  Coun*ng done by students. Hieracium •  Why was Hieracium a poor model system for studying inheritance? •  Its seed are purely maternal, there is no meiosis or fer*liza*on, so no recombina*on or segrega*on of alleles. 4 1/24/13 Variega*on and Soma*c Muta*on •  Variega*on was a source of confusion when sor*ng out segrega*on paLerns (de Vries, Correns, figured out by Emerson). 1.  Posi*on effect variega*on 2.  Variega*on due to soma*c muta*on –  Barbara McClintock discovered transposable elements while studying chromosome breakage at Cold Spring Harbor in the 1950’s. Transposable elements are mobile regulatory elements •  Dissociator locus is under the control of Ac+vator. •  Mobiliza*on of Ds out of the colored gene results produces clones with pigmenta*on. •  Transposable element mobiliza*on has phenotypic consequences. –  Soma*c mosaicism McClintock, 1951 h1p://old.weedtowonder.org/mcclintock/ds_jumps.html 5 1/24/13 Consequences of soma*c mosaicism •  Random X-­‐inac*va*on •  Cancer •  Variable expressivity Outline •  Inheritance / Transmission gene*cs –  Mendel & classical gene*cs •  Meiosis: mechanism that unites inheritance and chromosomes –  Chromosomal theory of inheritance, Walter SuLon •  Muta*on –  Morgan and Muller •  Characteris*cs of Phenotypes and Non-­‐Mendelian Inheritance –  Non-­‐Mendelian inheritance –  Gene*cs vs epigene*cs •  Popula*on gene*cs: study of gene*c varia*on in popula*ons 6 1/24/13 Walter SuLon: Evidence for Mendel’s Principles •  Chromosomal theory of inheritance: chromosomes are the physical basis of gene*c inheritance. •  Evidence: –  Boveri: chromosomes are required for development to occur in sea urchins. –  SuLon: chromosomes appear in matched pairs in grasshoppers. •  “… the associa*on of maternal and paternal chromosomes in pairs and their separa*on in the reduc*on division may cons*tute the physical basis of heredity.” •  Described how random assortment fulfills Mendel’s law, and can explain observed varia*on in traits. Meiosis 7 1/24/13 Remember Meiosis •  Synapsis: close pairing of homologous chromosomes to form a bivalent; during prophase I when crossing over occurs. •  Meiosis I: reduc8on division, separa*on of… •  Meiosis II: separa*on of… Meiosis is where heritable gene*c varia*on is generated •  Ques*on 8: What is parental purity? •  Meiosis explains Mendel’s laws of inheritance. •  Meiosis is where inherited muta+ons occur. •  Ques*on 9: What is Su1on talking about on p8? 8 1/24/13 Nondisjunc*on •  Discovered by Calvin Bridges. •  Evidence for chromosomal theory. Outline •  Inheritance / Transmission gene*cs –  Mendel & classical gene*cs •  Meiosis: mechanism that unites inheritance and chromosomes –  Chromosomal theory of inheritance, Walter SuLon •  Muta*on –  Morgan and Muller •  Characteris*cs of Phenotypes and Non-­‐Mendelian Inheritance –  Non-­‐Mendelian inheritance –  Gene*cs vs epigene*cs •  Popula*on gene*cs: study of gene*c varia*on in popula*ons 9 1/24/13 T.H. Morgan’s Fly Room •  Originally an embryologist, became interested in the debate over the physical basis of inheritance. •  Established Drosophila as a gene*cs model system at Columbia. The Fly Room at Columbia T.H. Morgan and gene*c linkage •  Breed flies with spontaneous muta*ons to study their inheritance paLerns. •  By breeding the white eyed mutant males, Morgan confirmed the chromosomal theory of inheritance and the existence of sex chromosomes. •  Discovered “linked” genes. –  Linkage: the close physical proximity of two or more genes. –  Linkage disequilibrium: the tendency for two (or more) alleles to be inherited together. 10 1/24/13 Muller and Muta*on •  Discovered that X rays increase muta*on rate. •  Exploited use of the X chromosome to es*mate the rate of lethal muta*ons. •  Two sugges*ons: –  Muta*ons might be primarily due to background radia*on. •  Stadler reported that muta*on rate was 8x treated seeds compared to the control. •  Hanson & Heys extended this: studying radium they discovered that ioniza*on is responsible for muta*ons. –  The rela*on between dosage and muta*on rate might be exponen*al instead of linear. •  Stadler reported that muta*on rate increased linearly with dosage. •  Confirmed by Oliver who showed that by varying the dose/dura*on of exposure gave a linear curve rela*ng dosage to muta*on rate. Muller and Muta*on •  What new class of mutagen arose in the late 40’s? What sparked its study? Why was its use in research delayed for so long? –  Mustard gas was discovered as a mutagen by Auerbach and Robson in 1941. They found similari*es between phenotypes of those exposed to mustard gas and irradia*on. The work could not be published un*l 1946 when WWII was over because it was considered classified. 11 1/24/13 Outline •  Inheritance / Transmission gene*cs –  Mendel & classical gene*cs •  Meiosis: mechanism that unites inheritance and chromosomes –  Chromosomal theory of inheritance, Walter SuLon •  Muta*on –  Morgan and Muller •  Characteris*cs of Phenotypes and Non-­‐Mendelian Inheritance –  Non-­‐Mendelian inheritance –  Gene*cs vs epigene*cs •  Popula*on gene*cs: study of gene*c varia*on in popula*ons Characteris*cs of Phenotypes •  Phenotype: a measurable trait. •  Penetrance: the percentage of individuals of a given genotype that display a phenotype. –  BRCA1/BRCA2 •  Expressivity: the degree to which a phenotype is displayed in individuals of a given genotype. –  “Hemingway cat”: Polydactyly in cats is highly penetrant but has variable expressivity. 12 1/24/13 Mendelian Inheritance can give rise to complex phenotypes •  Incomplete/semi-­‐
dominance: when the phenotype of the heterozygote is intermediate to the phenotypes of each homozygote –  Snapdragon petal color •  Codominance: contribu*ons from both alleles visible in the phenotype. –  E.g. blood type alleles in human. Mendelian Inheritance can give rise to complex phenotypes •  Polygenic traits (complex traits) –  Mul*ple genes contribute to a phenotype. –  If penetrance or expressivity is < 100% other genes/modifiers may be involved. •  Genes involved in the phenotype usually follow Mendelian inheritance, but create complexity by different interac*ons that result from allelic varia*on. 13 1/24/13 Sex-­‐linked traits Mitochondrial Inheritance •  Once circular, 16kb “genome” per mitochondria. –  13 protein-­‐coding genes (for oxida*ve phosphoryla*on system). –  Muta*on rate is 100x higher than the nuclear genome. –  Heteroplasmy: many heterogeneous mtDNA genomes per cell. •  Non-­‐Mendelian inheritance –  Inherited strictly maternally, through the oocyte. –  Disease muta*ons tend to affect *ssues with high-­‐energy demands. •  E.g. Leber hereditary op*c neuropathy (LOHN): loss of vision, due to mtDNA muta*on. 14 1/24/13 Non-­‐Mendelian Inheritance •  Ques*on 10: What are Bateson’s three types of non-­‐Mendelian inheritance? •  Blended inheritance or con*nuous varia*on: mul*ple genes influence a trait. •  First crosses that breed true: All gametes of a self-­‐
fer*lizing species are iden*cal due to absence of the reduc*on division (no separa*on of homologous chromosomes). •  False hybrids: Loss of one set of parental chromosomes in the offspring, resul*ng in a haploid organism (parthenogenesis). Epigene*c Inheritance •  Epigene*cs: the ensemble of mechanisms that concurrently modify the chroma*n to stably or dynamically modulate gene expression without affec*ng DNA sequence. •  Epigene*c features transmiLed across genera*ons. Imprin8ng: DNA methyla*on marks preserved across genera*ons. Templa8ng: DNA methyla*on and histone marks preserved across cell division. 15 1/24/13 Epigene*c vs. Gene*c Inheritance •  Gene8cs – both the use of muta*ons and muta*onal analysis to study a given biological process and the study of the hereditary process itself. •  Epigene8cs – the study of molecular mechanisms that mediate environmental influences on gene produc*on or regula*on whose effects persist (are inherited mito*cally and/or meio*cally) when the environmental s*mulus is removed. Outline •  Inheritance / Transmission gene*cs –  Mendel & classical gene*cs •  Meiosis: mechanism that unites inheritance and chromosomes –  Chromosomal theory of inheritance, Walter SuLon •  Muta*on –  Morgan and Muller •  Characteris*cs of Phenotypes and Non-­‐Mendelian Inheritance –  Non-­‐Mendelian inheritance –  Gene*cs vs epigene*cs •  Popula*on gene*cs: study of gene*c varia*on in popula*ons 16 1/24/13 Popula*on Gene*cs •  The science of the mechanisms responsible for microevolu+on, or the study of gene*c varia*on in popula*ons. •  Phenotype: a measurable trait of an individual, which emerges from the interac*on of a genotype and its environment. –  Physical –  Gene*c Either can cause variable expressivity or penetrance. Popula*on Gene*cs •  Study of varia*on in reproduc*ve success –  Game*c –  Environmentally-­‐induced •  Evolu8on: change in allele frequencies in a popula*on over *me. 17 1/24/13 Compara*ve Gene*cs/Genomics •  Synteny: conserva*on of blocks of order within two chromosomes that are being compared, usually between species. QUESTIONS? 18