A Microscopic to Molecular Perspective in Modeling Chromosomes WORKSHOP LEARNING OBJECTIVES Educators attending this workshop will: o Support the NGSS student learning outcomes of three dimensional lesson design utilizing the: o Connecting Nucleotides to Chromosomes Kit© to: o Construct acrocentric, metacentric and submetacentric chromosomes o Create and analyze karyograms o Model and explain the process of mitosis o Model and explain the process of meiosis at the microscopic and molecular scale o Explain genetic variation through modeling o Learn something new and interesting that is for your own professional development. o HAVE FUN! WORKSHOP LEARNING OBJECTIVES What NGSS dimensions will be targeted? SEPs CCCs DCIs Asking Questions and Patterns LS1.A: Structure and Function Defining Problems Developing and Using Cause and Effect: LS1.B: Growth and Models Mechanism and Explanation Development of Organisms Constructing Explanations Scale, Proportion, and LS3.A: Inheritance of Traits and Designing Solutions Quantity Engaging in Argument LS3.B: Variation in Traits Structure and Function from Evidence Analyzing and Stability and Change Interpreting Data HOW DO WE KNOW WHAT WE KNOW? Part of a long and complicated history! Karl Wilhelm von Nägeli noted “transitory cytoblasts” while studying pollen formation in 1842. We now call these observed structures chromosomes! https://en.wikipedia.org/wiki/Carl_N%C3%A4geli Unfortunately, Nägeli made a name for himself by rejecting Gregor Mendel’s studies on inheritance and instead tenaciously holding on to his ideas of spontaneous generation and orthogenesis. Image taken from The Cell-theory: a Restatement, History, and Critique Part V. The Multiplication of Nuclei By JOHN R. BAKER (From the Cytological Laboratory, Dept. of Zoology, University Museum, Ox HOW DO WE KNOW WHAT WE KNOW? History continued . Walther Flemming is generally credited with describing the behavior of chromosomes during mitosis in 1882. Flemming gets special mention because he had the heart of a teacher! https://www.uni-kiel.de/grosse- forscher/index.php?nid=flemming&lang=e Consider this . An accurate count of human chromosomes didn’t occur until 1956 by Tjio and Levan! https://www.nature.com/scitable/content/drawing-of-mitosis-by- walther-flemming-43904 MULTIPLE MODELS OF CHROMOSOMES ANOTHER CHROMOSOME MODEL!?! Telomere YES! p arm Why you ask? Linker All shall be revealed in due time! Now let’s build some chromosomes! Centromere Linker q arm Telomere BUILD MODEL CHROMOSOMES Acrocentric Metacentric Submetacentric BUILD MODEL CHROMOSOMES Build a maternal and paternal set! Replicate your chromosomes! BUILDING MODEL CHROMOSOMES Completed Maternal and Paternal Chromosomes! n = 3 (haploid number of chromosomes) 2n = 6 (diploid number of chromosomes) MODEL KARYOGRAMS TO DETERMINE KARYOTYPE http://ib.bioninja.com.au/standard-level/topic-3-genetics/32-chromosomes/karyograms.html http://ib.bioninja.com.au/standard-level/topic-3-genetics/32-chromosomes/karyograms.html WHAT EXACTLY IS A CHROMOSOME? https://qph.fs.quoracdn.net/main-qimg- a5c27f2ff2b2ba120f64285d92a2f408-c Chromosome? Duplicated Chromosome? http://ib.bioninja.com.au/standard-level/topic-3-genetics/32-chromosomes/karyograms.html Chromatid? Chromatin? Centromere? BUT where’s the DNA? PUT ON YOUR MOLECULAR SPECTACLES! What can this model do to expand the concept of the chromosome? Replicated Chromosome at the Nucleotide Level! MODELING MITOSIS TO ANSWER AN ESSENTIAL QUESTION How are characteristics passed from one generation of cells to the next? Cell division for growth and repair of somatic (body) cells Mitosis Genetic information is maintained! How does the model allow me to see that the genetic information is maintained? AND SPEAKING OF INHERITANCE. Why do we all look different? https://www.ecald.com/updates/indian-and-south-asian-families-support- caring-for-their-disabledspecial-needs-family-members-monthly-support- group-meeting-28th-july-2016/ http://pozboysg.tumblr.com/post/28550047424/janices-story-my-life-with-a-hiv-family-member http://lovefromthedesert.blogspot.com/2010/10/redhouse-family.html https://nypost.com/2015/03/02/meet-the-bi-racial-twins-no- http://statchatva.org/2013/10/16/multigenerational-households/ https://altright.com/2018/01/24/race-is-just-your-extended-family/ one-believes-are-sisters/ GENERATING GENETIC VARIATION DURING MEIOSIS If the chromosomes line up like this . you get gametes like this. GENERATING GENETIC VARIATION DURING MEIOSIS If the chromosomes line up like this . you get gametes like this. GENERATING GENETIC VARIATION DURING MEIOSIS If the chromosomes line up like this . you get gametes like this. GENERATING GENETIC VARIATION DURING MEIOSIS If the chromosomes line up like this . you get gametes like this. GENERATING GENETIC VARIATION DURING MEIOSIS Due to independent assortment of chromosomes, in a cell where the haploid number of chromosomes equals 3 or 2n = 6, the number of different chromosomal arrangements in the daughter cells is 8! GENERATING GENETIC VARIATION DURING MEIOSIS The number of possible combinations when chromosomes sort independently during meiosis is 2n, where n is the haploid number of chromosomes in the organism. In humans, the number of possible combinations of maternal and paternal chromosomes in the resulting sex cells is 223, or approximately 8.4 million! WOW! That’s a lot of variation WITHOUT any crossing over! PUT ON YOUR MOLECULAR SPECTACLES! DNA Replication! PUT ON YOUR MOLECULAR SPECTACLES! Now let’s talk about inheritance! PUT ON YOUR MOLECULAR SPECTACLES! Why the one gray nucleotide? Now you can connect the Punnett Square to a nucleotide sequence! https://edu.glogster.com/glog/sickle-cell-anemia/2bbb3vtjfok PUT ON YOUR MOLECULAR SPECTACLES! Now Connect the Nucleotide Sequence to Protein Structure! GENERATING EVEN MORE GENETIC VARIATION CROSSING OVER ❖ The “swapping” of chromosome parts between homologous chromosomes ❖ Typically shown between two adjacent sister chromatids https://qph.fs.quoracdn.net/main-qimg- a5c27f2ff2b2ba120f64285d92a2f408-c GENERATING EVEN MORE GENETIC VARIATION CROSSING OVER Can the “outside” chromatids cross over? They can indeed! OR Alignment of chromosomes happens in 3 dimensional space. https://qph.fs.quoracdn.net/main-qimg- a5c27f2ff2b2ba120f64285d92a2f408-c GENERATING EVEN MORE GENETIC VARIATION Modeling “Traditional” Microscopic Meiosis Crossing Over Homologous Sister chromatids Chromatids chromosomes line up. cross over. exchange parts. MOLECULAR CROSSING OVER Consider “molecular meiosis”. Homologous chromosomes align. MOLECULAR CROSSING OVER Begins with a BOLD step. A specialized protein makes a double stranded break in one chromosome. MOLECULAR CROSSING OVER 5’ to 3’ nuclease digests one strand from each end of the cut, one nucleotide at a time. MOLECULAR CROSSING OVER Homologous DNA sequence is “unzipped”. MOLECULAR CROSSING OVER Strand invasion occurs. MOLECULAR CROSSING OVER DNA polymerase uses homologous chromosome as the template to fill in the gaps (note gray nucleotides). MOLECULAR CROSSING OVER Single-stranded cuts in the chromosome that was used as the template (the red chromosome). MOLECULAR CROSSING OVER Ligase joins breaks in the DNA to form two recombinant chromosomes. MODELING CROSSING OVER Microscopic Crossing Over Molecular Crossing Over According to the 4th edition of Molecular Biology of the Cell, on average, between two and three crossover events occur on each pair of human chromosomes during meiotic division I. Think of the additional variation generated with crossing over! MODELING CHROMOSOMAL ABERRATIONS Microscopic Scale Molecular Scale For example: Translocation MODELING OTHER CHROMOSOMAL ABERRATIONS Students can think with models to show additional aberrations like . Microscopically AND Molecularly MODELING NONDISJUNCTION When NONDISJUNCTION occurs during Meiosis I . RESULT? No gametes with the correct number of chromosomes! n - 1 OOPS! n + 1 MODELING NONDISJUNCTION When NONDISJUNCTION occurs during Meiosis II . RESULT? Some gametes have the correct number of chromosomes and some do NOT! n n - 1 n + 1 OOPS! DIVING DEEPER WITH MODELS With their molecular spectacles firmly in place. Guide students to think with models: How do chromosomes “find” their homologs during meiosis? https://opentextbc.ca/biology/chapter/6-1-the-genome/ HOW DO CHROMOSOMES FIND THEIR HOMOLOGS? The bouquet arrangement in hexaploid wheat. ❖ Telomeres are the same ❖ Why? ❖ Bouquet ❖ Begin pairing at ends Carrie R. Cowan et al. Plant Physiol. 2001;125:532-538 ©2001 by American Society of Plant Biologists JUST WHEN YOU THOUGHT YOU UNDERSTOOD CELL DIVISION . Two separate mitotic spindles Reichmann et al., Science 361, 189–193 (2018) 13 July 2018 A New Way to Think About First Mitosis Zielinska et al., Science 361, 128-129 (2018) 13 July 2018 THANK YOU! HOW CAN I GET THESE GREAT MODELS? Coming SOON this Fall PURCHASE from 3D Molecular Designs: https://www.3dmoleculardesigns.com/Education-Products.htm Be sure to use your 20% show special discount code: STEM19 BORROW from the Model Lending Library: http://cbm.msoe.edu/lendingLibrary/index.php THANK YOU! For more molecular stories. Come visit us at booth 501! We hope to see you soon!.