BIOL 2500: Genetics 1 (F24) Lecture 1 - Cell Division PDF

1 BIOL 2500: Genetics 1(F24) Topic 1: Introduction and Cell Division Concepts: 1.1-1.3, 2.2-2.3 © Jennifer Doering 2024 2 Treaty Acknowledgement  The University of Manitoba campuses are located on original lands of Anishi...

1 BIOL 2500: Genetics 1(F24) Topic 1: Introduction and Cell Division Concepts: 1.1-1.3, 2.2-2.3 © Jennifer Doering 2024 2 Treaty Acknowledgement  The University of Manitoba campuses are located on original lands of Anishinaabeg, Ininiwak, Anisininewuk, Dakota Oyate and Dene, and on the National Homeland of the Red River Métis. National Centre for Truth and Reconciliation  We respect the Treaties that were made on these territories, we acknowledge the harms and mistakes of the past, and we dedicate ourselves to move forward in partnership with Indigenous communities in a spirit of reconciliation and collaboration.  As a white female of settler descent from the unceded ancestral territories of the Lheidli T’enneh of Northern British Columbia, I am committed to learning about Indigenous history, understanding the harms and wrongs of the past, and working towards reconciliation and collaborations with all Indigenous people on whose lands I am grateful to call home. © Jennifer Doering 2024  BECOME A VOLUNTEER NOTETAKER Why? Help reduce barriers for your peers Contribute to creating an inclusive University of Manitoba Receive recognition on your Experience Record How? Login and upload your notes directly at https://sasclockwork.cc.umanitoba.ca/ClockWork/ Submit notes in your preferred style (typed or handwritten) It only takes an extra 15 minutes weekly http://umanitoba.ca/student-supports/accessibility IN THE CASE OF A FIRE ALARM: Remain calm if it is safe, evacuate the classroom or lab go to the closest fire exit do not use the elevators If you need assistance to evacuate the building, inform your professor or instructor immediately. If you need to report an incident or a person left behind during a building evacuation, report it to a fire warden or call security services 204-474-9341. Do not reenter the building until the “all clear” is declared by a fire warden, security services or the fire department. Important: only those trained in the use of a fire extinguisher should attempt to operate one! umanitoba.ca 5 Classroom Etiquette  I strive to create a safe space where we all can come together and learn how cool biology is  Inappropriate behaviours are not tolerated  Respectful Work and Learning Environment Policy  Let’s keep each other healthy  Masking is strongly encouraged in this class  I will be wearing my mask when teaching  Please stay home if you are ill  Disrespectful behaviours to those who choose to wear or not wear a mask will not be tolerated  Let’s strive for a community of caring and respect  DO NOT post your lecture notes, assignments, quizzes, etc. to note sharing sites such as Studocu, CourseHero, Chegg, etc.  It violates copyright and can be considered as non-academic misconduct © Jennifer Doering 2024  Academic Integrity What is Academic Integrity? Academic Integrity in Genetics Penalties for Academic Misconduct Honesty Don’t submit other group First offence Trust Handled at the Department members’ work as your own Fairness Make sure to use only Grade of 0 on the exam or Respect assignment authorised resources during Responsibility A letter in your file exams and assignments Courage Read the syllabus! Second offence Do not upload assignments, Handled at the Faculty Adds value and credibility F in the course with lecture notes, etc. to other to your degree! websites (i.e. Chegg, (DISC)ipline notation on your StuDocU, CourseHero, etc.) transcript Academic Dishonesty This list is not exhaustive! Banned from taking Science Inappropriate collaboration courses for 1 year Resources on Academic Integrity Plagiarism On a Final Exam It is your responsibility to Impersonation Handled at the Faculty know of the policies of Using unauthorised resources (including F in the course with Academic Integrity ChatGTP/AI) (DISC)ipline notation on your https://umanitoba.ca/student- Duplicate submission transcript supports/academic- Contract cheating Banned from taking Science supports/academic-integrity Academic fraud courses for 1 year Ask me if you have questions! © Jennifer Doering 2024 7 Instructor Information  Instructor: Ms. Jennifer Doering (please call me Jennifer or Ms. Doering), she/her  Email: [email protected]  Student Hours: W365 Duff Roblin  Monday, 11:30am-1:30pm  Thursday, 11:30am-1:00pm  Can also email for an appointment  I will do my best to respond to all emails within 24-48 hours, except evenings, weekends, holidays, and exam days  Lecture/course-related questions could be posted to the Discussion Forums ☺  Lectures: TR 2:30pm-3:45pm  Tutorials: T 10:00-11:15am (B01) and R 10:00-11:15am (B02)  Tutorial handouts will be posted on UM Learn  Labs start week of September 10th (Sep 10th/12th) © Jennifer Doering 2024  8 A little about me….. Skunks are one of my  BSc (Honours) Biological Sciences, with a minor in Physical favourite animals Geography Cladonia borealis, a  Thesis: Chemical ecology in boreal terrestrial lichens common Pixie cup lichen  Specialties: botany, lichenology, statistics, field work, geographic information systems  MSc Biological Sciences  Thesis: Inferring gene flow in semi-aquatic lichens using population genetics  Specialties: lichenology, population genetics, field work, multivariate I really like coffee statistics I like to draw Field work is one of my and paint favourite parts of biology © Jennifer Doering 2024 9 Syllabus  A syllabus is your guide in a course. It covers important things such as how much assignments are worth, when midterms are, etc.  We’re not going to go over all of it today, so….  It’s REALLY important to read it!  Most of the answers to basic questions about the course can be found in the syllabus. **You will need to complete the Syllabus Quiz to gain access to course materials  The syllabus can be found under ‘Course Syllabus and Info’ on UM Learn.  Lecture PDFs  Study Resources © Jennifer Doering 2024 10 Syllabus © Jennifer Doering 2024 11 Textbook  Introduction to Genetic Analysis, 12th ed. by Griffiths et al. (2020), MacMillan Learning Purchasing options (choose one) 1. Loose leaf book with Achieve Access - $170 ISBN: 9781319424015 2. E-Text with Achieve Access - $107.50 ISBN: 9781319401405 Please note, we will be using Achieve to complete several assignments this term A booklet of practice problems is also posted to UM Learn under the Content -> Study Resources tab © Jennifer Doering 2024 12 Textbook – The Bookstore has it! © Jennifer Doering 2024 13 Course Schedule © Jennifer Doering 2024 14 Course Schedule © Jennifer Doering 2024 15 Course Breakdown  There are two types of Achieve Assignments  9x Topic Assignments  3x Reflection and Goal Setting surveys  Check UM Learn for the Achieve Assignment Schedule  Written Assignments  These are submitted as PDFs on UM Learn in the Assignments tab  Typically, due 1 week after opening (schedule on page 7 of the syllabus)  You will receive feedback on your assignments to help inform your studying © Jennifer Doering 2024 16 Housekeeping Notes  Upcoming Assignments  Achieve Assignment #1 is open today  Achieve Reflection Survey 1 (Intro Survey) is open today  DUE: Sept. 20th, 11:59pm  Written Assignment (WA) #1: Data Survey is open today  We need some data for tutorials later in the term  Will be collecting blood type data, heights  DUE: Sept. 27th, 11:59pm  Tutorials begin Tuesday, Sept. 10th and Thursday, Sept. 12th  Materials will be posted around the weekend so you can read the tutorial ahead of next week  Material covered in the tutorials will form some of the basis of your written assignments © Jennifer Doering 2024 17 1.1 People have observed patterns of inheritance  “Like begets like”  People have always observed familial patterns  Children look like parents  Red-seeded maize when planted produced red-seeded maize in the next crop  People used to think traits were “blended together” when inherited from parents  What is the problem with this idea?  Is it 100% incorrect?  Gregor Mendel is considered the “Father of Genetics”  Inheritance was “particulate” © Jennifer Doering 2024 18 1.1 Modern genetics is in its second century 1905: The term “Genetics” is 1940s: DNA is elucidated to be defined by William Bateson the genetic material 2001: First Human Genome is sequenced 1908: Hardy- Weinberg principle 1977: DNA 1909: The term Sequencing “gene” is defined technology developed 1910: Sex-linkage and recombination is recognised https://scienceofhealthy.com/history-genetics/ 1930s Evolutionary synthesis © Jennifer Doering 2024 19 1.1 Genetics is the study of inheritance  Genes are the physical units of heredity, that collectively control gene transcription of DNA to RNA and therefore translation to proteins  Central Dogma of molecular biology (DNA -> RNA -> protein)  Genes are contained in chromosomes, consisting of single long molecules of double-stranded DNA contained within the nucleus and is inherited through cell division  If organisms have 2 copies of each gene, they are diploid  Have homologous pairs of chromosomes  If organisms only have 1 copy of each gene, they are haploid  Some organism have more than 2 copies -> polyploid  Genetic information (DNA and RNA) can also be contained within chloroplasts (plants) and mitochondria (plants and animals)  Cytoplasmic inheritance as the mitochondria and chloroplasts are distributed to daughter cells during cytokinesis © Jennifer Doering 2024 20 1.1 Genetics is central to modern biology  Genes code for various functions within cells  Genotype is the genetic make-up of the organism  Phenotype is the observable traits dictated by the genotype  Controlled by variations in genes called alleles  Three main subdisciplines of genetics  Transmission genetics  “Mendelian” genetics -> transmission of traits and characteristics between successive generations (inheritance)  Evolutionary genetics  Studies the origins of and genetic relationships between organisms and the evolution of traits and genes/genomes  Molecular genetics  Studies inheritance and variation in nucleic acids (DNA and RNA), proteins, and genomes and connects them to inherited variation and evolution in organisms © Jennifer Doering 2024 21 1.2 Geneticists use Model Organisms to study inheritance  Model organisms are species that are studied with the presumption that knowledge gained can be applied to other similar organisms  E. coli (bacterium)  Drosophila melanogaster (fruit fly)  Arabidopsis thaliana (thale cress)  Caenorhabditis elegans (roundworm)  Neurospora spp. (fungus)  Mus musculus (mouse)  What makes a good model?  Small size  Small genome  Large #’s of offspring  Short generation times © Jennifer Doering 2024 22 1.3 Genetics in the modern world  “You have this clear, tangible phenomenon in which children resemble their parents. Despite what students get told in elementary-school science, we just don’t know how that works” ~Leonid Kruglyak, 2008  Genetics is constantly evolving  Classical genetics stemmed from Mendel’s experiments  Medical genomics  Using modern molecular tools to understand human diseases and conditions  DNA sequencing to identify SNPs in the genome  Understanding how mutations affect phenotypes  Genetically modified organisms, gene editing, DNA transformations  Using genome-wide association studies (GWAS) to understand human evolution © Jennifer Doering 2024 23 2.2 Eukaryotes exhibit two kinds of cell division  Somatic cell division occurs in somatic cells  What do also know this type of cell division to be?  What is the product of this type of cell division?  Sexual cell division occurs in sex organs to produce gametes via the division of meiocytes (germ-line cells)  Animals and plants: sperm (male) and eggs (female)  Fungi and algae: sexual spores  Genetically unique due to recombination during division © Jennifer Doering 2024 24 2.2 Ploidy level  Animals are diploid organisms (2n or 2N)  They have 2 copies (or chromosomal sets) of each of the chromosomes in their genomes  The “n” refers to the number of chromosomes  The “2” refers to how many sets of each chromosome are present in the nucleus  Humans are 2N = 46  We have 23 unique chromosomes, but two sets of each  Bacteria, algae, and fungi are often haploid organisms (1n or 1N)  Plants and some animals are polyploid (>2n or >2N)  Triploid: 3N  Tetraploid: 4N  Dodecaploid: 12N © Jennifer Doering 2024 25 2.2 The Cell Cycle  Cell division is controlled by the cell cycle  M-phase -> Cell division  Interphase -> Gene expression (so not a “resting stage”)  G1 – “Gap 1”, Gene expression is high  S – “Synthesis” phase, DNA replication occurs here  Doubles the DNA content by creating two sister chromatids (i.e. duplicated chromosomes)  G2 – “Gap 2”, cell prepares to divide  G0 – Some specialised cells enter this phase and do not go on to cell division  Gene expression continues  No longer progress through the cell cycle  Ex. Bone cells, eye cells © Jennifer Doering 2024 26 2.2 Cell division is controlled by check points  4 main checkpoints:  G1 checkpoint: Pass if cell size is adequate, nutrients availability is good, presence of growth factors  S-phase checkpoint: Pass if DNA replication is complete and base-pair mismatches/errors are removed  G2 checkpoint: Pass if cell size is adequate, chromosome replication is complete  Metaphase checkpoint: Pass if all chromosomes are attached to the mitotic spindle  Mutations that alter the cell cycle or checkpoints can lead to cancer, and other diseases © Jennifer Doering 2024 27 2.2 Mitosis © Jennifer Doering 2024 28 2.2 Interphase (G2)  Chromosomes are diffuse and not visible (called chromatin)  Chromosomes are duplicated (already went through S-phase)  Nuclear envelope still encloses the nucleus  Two centrosomes are in the cytoplasm  Microtubules begin to extend © Jennifer Doering 2024 29 2.2 Prophase  Chromosomes begin to condense and become visible  Sister chromatids attached via centromeres visible  Pair centrosomes move to the poles  Microtubules extend from centrosomes to form mitotic spindle  Nucleolus disappears © Jennifer Doering 2024 30 2.2 Prometaphase  Nuclear envelope breaks down  Mitotic spindle attaches to kinetochores of the sister chromatids  Microtubules begin exerting pulling forces in both directions  Chromosomes begin to move to center of the cell  Cohesin proteins bind sister chromatids together  Resists premature separation  Nonkinetochore and astral microtubules stabilise the cell © Jennifer Doering 2024 31 2.2 Metaphase  Chromosomes fully condensed  Chromosomes align to metaphase plate  Sister chromatids are still attached to kinetochore microtubules extended from centrosomes  Mitotic spindle fully developed © Jennifer Doering 2024 32 2.2 Anaphase  Sister chromatids separate (disjunction)  Cohesin proteins break down  Kinetochore microtubules depolymerise  Daughter chromosomes move towards opposite poles and congregate at centrosomes  Nonkinetochore and astral microtubules polymerise, elongating the cell © Jennifer Doering 2024 33 2.2 Telophase and Cytokinesis  Nonkinetochore microtubules continue polymerising, elongating the cell  Nuclear envelope redevelops  Chromosomes decondense  Cytokinesis divides the cytoplasmic contents equally between the daughter cells  Forms a cell plate in plants  Forms a contractile ring and cleavage furrow in animals  Nucleolus reforms © Jennifer Doering 2024 34 2.2 Keeping tab on DNA during mitosis  If we start with 2 ng of DNA in 2N=46 at G1 then:  After S phase, the DNA content doubles: 4 ng DNA content  After anaphase (M phase), the DNA content is halved: 2 ng DNA content © Jennifer Doering 2024 35 2.2 Meiosis has two rounds of cell division  Germ-line cells have identical interphase as somatic cells  Structures such as centrosomes, spindle fibres are the same  Germ-line cells are replenished via mitosis, but undergo meiosis to produce gametes  2 main divisions, with no DNA replication in between  Meiosis I – homologous chromosomes separate, ploidy level reduces by half  i.e., 2N -> 1N  Meiosis II – sister chromatids separate  Duplicated chromosomes reduce to single chromosomes (i.e., no sister chromatids) © Jennifer Doering 2024 36 2.2 Meiosis I  3 hallmark events occur: 1. Homologous chromosome pairing  Chromosome synapsis 2. Crossing over between homologous chromosomes  Results in recombination at cross-over sites called chiasmata 3. Segregation (separation) of homologous chromosomes (ploidy level reduced by half)  Divided into 4 stages:  Prophase I -> homologous pairing and cross-over, occurs over 5 substages  Metaphase I -> aligning to the centre of the cell  Anaphase I -> separation of homologous chromosomes  Telophase I and cytokinesis -> end of first division © Jennifer Doering 2024 37 2.2 Prophase I and crossing over  Leptotene  Chromosomes are duplicated (having passed S-phase)  Chromosomes condense into long, single threads  Centrosomes migrate to poles  Spindle fibres produced  Zygotene  Chromosomes continue condensing and begin forming pairs  Homologous pairs enter synapsis, forming the synaptonemal complex  Meiotic spindle forms  Nuclear envelope beings to break down © Jennifer Doering 2024 38 2.2 Prophase I continued  Pachytene  Chromosome condensation partially complete  Synapsed homologs are seen as bivalents (tetrads)  Crossing over occurs between non-sister chromatids, formation of chiasmata  Kinetochore microtubules attach to the kinetochores  Nuclear envelope breakdown continues  Diplotene  Crossing over is complete  Synaptonemal complex dissolves but chiasmata remain  Tetrads completely visible  Nuclear envelope fully dissolved © Jennifer Doering 2024 39 3.2 Prophase I and Metaphase I  Diakinesis (Prophase I)  Meiotic spindle established  Homologous chromosomes tethered to poles via spindle fibres  Nuclear envelope fully degraded  Tetrads begin to move to cell middle  Metaphase I  Tetrads align to metaphase plate  Homologous pairs tethered to opposite poles  Kinetochores od sister chromatids are attached to the same centromere, joined by cohesion proteins to prevent premature separation  Chiasmata linking non-sister chromatids broken  Allows recombination via independent assortment  2(n-1) possible combinations, where n = number of homologous pairs © Jennifer Doering 2024 40 3.2 Anaphase I and Telophase I  Anaphase I (segregation of alleles)  Kinetochore microtubules depolymerise  Disjunction occurs, pulling homologs to opposite poles  Sister chromatids remain attached by cohesion  Ploidy level has now been reduced by half  Telophase I and Cytokinesis  Nuclear membrane re-form around chromosomes  Chromosomes partially decondense  Cytokinesis divides the cytoplasmic contents, which may be unequal  Progeny cells are now haploid (n)  Sometimes the cell will enter interkinesis © Jennifer Doering 2024 41 2.2 Meiosis II  Prophase II  Nuclear envelope breaks down  Centrosomes duplicate and migrate to poles  Microtubules form  Chromosomes recondense  Metaphase II  Sister chromatids attached to kinetochore  Align at metaphase plate  Not as pressed tightly together as they are in mitosis © Jennifer Doering 2024 42 2.2 Meiosis II  Anaphase II  Sister chromatids separate, breakdown of cohesin proteins  Kinetochore microtubules depolymerise  Sister chromatids move to opposite poles  Nonkinetochore microtubules elongate the cell  Telophase II and Cytokinesis  Chromosome migration complete  Chromosomes decondense  Nuclear envelope reforms  Cytokinesis divides the cytoplasm © Jennifer Doering 2024 43 2.2 Meiosis Overview © Jennifer Doering 2024 44 2.2 Keeping tab on DNA during meiosis  If we start with 2 ng of DNA in 2N=46 at G1 then:  After S phase, the DNA content doubles: 4 ng DNA content, with duplicated chromosomes  i.e., 2 chromatids per chromosome  After anaphase I, the DNA content is halved: 2 ng DNA content, but chromosomes are still duplicated  Twice the number of chromatids still  After anaphase II, the DNA content is halved again, and chromatids no longer doubled © Jennifer Doering 2024 45 2.2 Mitosis vs Meiosis  Can you add more details to this chart? Characteristic Mitosis Meiosis Purpose Location Number of Divisions Homologous Chromosomes Sister Chromatids Product  Compare DNA content between the two! © Jennifer Doering 2024 46 2.3 Meiosis and mitosis at the molecular level  Replication of DNA during S phase produces 2 copies of each chromosome (i.e., produces sister chromatids)  Therefore, it also produces 2 copies of each allele  Each allele usually only differs by a single or few nucleotide base © Jennifer Doering 2024 47 2.3 Meiosis and mitosis at the molecular level © Jennifer Doering 2024 48 2.3 Meiosis and mitosis at the molecular level © Jennifer Doering 2024