Biology 321 Genetics Winter 2009

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1 Biology 321 Genetics Winter 2009 Dr. Sandra Schulze Office BI409 Office Hours: WF 4:00PM 5:00PM Grading Exam I: 25% Exam II: 25% Exam III: 25% Problem sets 25%* No specific grades for attendance or participation, BUT if your grade is border line and you were active in these categories I will bump you to a higher grade *QUIZ FRIDAY on mitosis and meiosis this quiz will count as one problem set! 1

2 Assignments Seven problem sets (one quiz plus six take-home sets) throughout the quarter Reading assignments and MORE problems from the text/my fevered brain This course requires both LEARNING FACTS and SOLVING PROBLEMS Exams will be sometimes similar, sometimes quite different from the problem sets and text book, but the principles you use to solve them will be the same! At the end of the year I will grade ONE or TWO problems from each set this will form 25% of your final grade. How will we use the class time? 3 days a week, 1hr 20m per lecture Break in middle of lecture, or leave 5 minutes earlier? VOTE! Fridays: assigned problem sets due AT THE BEGINNING OF CLASS!!! Wednesdays: will include both lecture and tutorial. 2

3 Course Goals Introduction to some new concepts (learning new facts) Problem solving (using lots of facts) Critical thinking (privileged knowledge) 3

4 Course Overview Mitosis! Meiosis! Transmission Genetics Model organisms, Mendel, complications to Mendel, recombination, human pedigrees Prokaryotic Genetics Mechanisms of DNA exchange in Bacteria, mapping in E.coli Molecular Genetics DNA and information storage, molecular basis of mutation, molecular techniques, positional cloning Special topics Surprise surprise? Let s dive right into the (gene) pool! Lecture 1: Mitosis and Meiosis 4

5 Cell division Prokaryotic cell division Eukaryotic cell division chromosomes Prokaryotes and Eukaryotes Bacteria Archaea Eukarya THEM (also this course (a bit)) US (and this course) 5

6 Prokaryotic vs eukaryotic cells Prokaryotic vs. eukaryotic cell size 6

7 Prokaryotic chromosome Eukaryotic chromosomes 7

8 Bacterial chromosome Human chromosome NOT to scale!!! replicated chromosome (can you see why?) Chromosomes Chromosomes are (usually) LONG pieces of double stranded DNA Can be linear (eukaryotic) or circular (prokaryotic) Can be complexed with proteins (chromatin) or almost naked nucleic acid Chromosome number can vary widely Cells (and organisms) with two pairs of every chromosome in a set are diploid Cells (and organisms) with only one of each chromosome in a set are haploid 8

9 Genomes chromosomes, genomes and genes The genome is the total information content represented by a single set of chromosomes Genome organization = the way in which this information is broken up and distributed over the chromosomes Information includes genes which are sequences of DNA located at specific positions along the chromosomes 9

10 Prokaryotic vs. eukaryotic genomes Organism Genome Size # of Genes Chromosomes (n) (n) Human 3,000,000,000 35, linear D. 140,000,000 13,600 4 linear melanogaster C. elegans 97,000,000 19,000 6 linear A. thaliana 125,000,000 25,500 5 linear S. cerevisiae 13,000,000 5, linear E. coli 4,700,000 4,000 1 circular Human mtdna 17, circular Prokaryotic vs. eukaryotic genome organization Bacterial genome is organized into a single (usually) circular chromosome that is relatively small (~10 6 bp) Eukaryotic genome is arranged in a series of linear chromosomes that vary widely in size 10

11 Chromosome number: haploid, diploid, polyploid Talking about the number of chromosome sets that represent the genome information content of an organism The haploid set of chromosomes in an organism is a certain number = n In diploid organisms, where the chromosomes come in pairs, the total number of chromosomes is 2n Some organisms (some plants, some fish etc) are polyploid they have multiple sets of chromosomes Diploid vs. haploid life cycle Animals like us Plants etc. 11

12 Humans are diploid two of each chromosome homologous pairs Homologous chromosomes Members of a chromosome pair that contain the same genes Each member is called a homolog One is inherited from each parent (so they are not identical) Chromosomes that contain different genes are non-homologous 12

13 humans are diploid two of each chromosome homologous pairs Homologous pair of chromosomes humans are diploid two of each chromosome homologous pairs Non-homologous pair of chromosomes 13

14 Autosomes and sex chromosomes In many eukaryotes, the sexes differ with respect to a single chromosome pair these are the sex chromosomes In one sex they match (are homologous), and in the other they do not All the other chromosome pairs are autosomes Human males are diploid, with unmatched sex chromosomes (XY) 14

15 chromosome number: euploidy Multiples of basic chromosome set. Haploids, diploids are euploid. Polyploids are also euploid: Triploids Tetrapoloids Pentaploids Hexaploids etc. Wheat varieties are polyploid multiples of whole chromosome sets Diploid, 2n=14 Tetraploid, 4n=28 Hexaploid, 6n=42 15

16 chromosome number: aneuploidy Changes in number of individual chromosomes, relative to the normal diploid number of two. Hyperploid, increase in chromosome number (trisomy, etc.) Hypoploid, decrease in chromosome number (monosomy, nullosomy) Aneuploidy is not usually a good thing Trisomy 21 (Down s Syndrome) 16

17 The cell cycle and mitosis Cell division Interphase Time for cell division: no gene expression Time for replication, transcription MITOSIS 17

18 Chromosomes and chromatids S phase centromere Non sister chromatids After the chromosomes replicate during S phase, two sister chromatids are joined together by the centromere When sister chromatids separate during mitosis, they can still be called chromatids but more accurately they are daughter chromosomes So what is a chromosome??? At the end of S phase, a cell has twice as many chromatids as there are chromosomes in the G 1 phase A human cell for example has: 46 distinct chromosomes in G 1 phase 46 pairs of sister chromatids in S phase Therefore the term chromosome is relative In G 1 and late in the M phase, it refers to the equivalent of one chromatid In G 2 and early in the M phase, it refers to a pair of sister chromatids joined at the centromere 18

19 Prophase Centriole Microtubules Centrosome Centromere Chromosome In animal cells Sister chromatids Nuclear envelope Chromosomes condense and become visible Sister chromatids attached at centromere Spindle apparatus forms outside of nucleus Microtubules (tubulin) parallel to the cell axis Centrosomes, composed of centrioles and pericentriolar material, form the spindle poles Nucleoli disappear Prometaphase Astral microtubules Kinetochore Kinetochore microtubules Polar microtubules Nuclear envelope breaks down, vesiculates Microtubules extend into nucleus Kinetochore microtubules attach to kinetochores Sister chromatids attach to opposite poles 19

20 Metaphase Metaphase plate (equatorial plane) Chromosomes form bipolar attachments and move to the metaphase plate (equatorial plane) Sister chromatids face opposite poles Anaphase Separating sister chromatids Centromeres divide first and start to separate Sister chromatids separate and move along microtubules to opposite spindle poles After migration of sister chromatids (now daughter chromosomes) to their respective poles, the spindle poles separate further 20

21 Telophase Re-forming nuclear envelope Chromatin Nucleoli reappear Nuclear envelope reforms around each set of chromosomes Chromosomes de-condense Nucleoli reappear Spindle disperses Cytokinesis Contractile ring forms around the equator of the cell, forms a cleavage furrow, then divides the cell into two halves (animal cells) Genetic material (chromosomes) and cytoplasm are divided equally into two daughter cells cleavage furrow 21

22 The cell cycle, ploidy, and DNA content during mitosis Chromosomes and genomes Before replication How many chromosomes are here: 2n=? How many before DNA replication? How many after replication? Hint: count centromeres

23 Chromosomes and genomes Before replication If before replication, there are two genomes in a diploid cell, how many genomes after replication but before cell division? 4 genomes Chromosomes and genomes Before replication If before replication, there are four chromosomes in a diploid cell, how many chromosomes after replication but before cell division? If the centromeres have separated, a temporary 4n stage (4n=8 chromosomes) And the number of chromosomes equals the number of chromatids 23

24 Purpose of Mitosis? Parent cell is diploid (2n=2) 2n Homologs don t usually pair at mitosi Chromatids separate (4n) Daughter cells are diploid (2n=2) leads to daughter cells with the same DNA content (barring rare somatic mutations), same number of chromosomes as the parent cell Summary of Mitosis for 2n=2 Start with 1 cell (2 chromosomes, 2 chromatids) DNA replicates during S phase (2 chromosomes 4 chromatids) Sister chromatids separate at Anaphase (4 chromosomes, 4 chromatids) After Telophase and Cytokinesis, finish with 2 daughter cells (both 2 chromosomes, 2 chromatids) 24

25 If everything was mitotic. life would be pretty dull. FORTUNATELY! THERE IS MEIOSIS!!! 25

26 Like mitosis, meiosis begins after a cell has progressed through interphase of the cell cycle Unlike mitosis, meiosis involves two successive divisions These are called Meiosis I and II Each of these is subdivided into Prophase Metaphase Anaphase Telophase MEIOSIS Homologs pair on metaphase plate (each homolog consists of two sister chromatids) Reductive division Mitotic division Daughter cells have one homolog from each pair. But each homolog still consists of two sister chromatids. 26

27 Meiosis is a reductive division Daughter cells have half the chromosome complement of parent cells Daughter cells become gametes (the only truly immortal cells ) Meiosis is a reductive division Daughter cells have half the chromosome complement of parent cells Daughter cells become gametes (the only truly immortal cells ) MOM YOU DAD 27

28 Homologous chromosome pairs undergoing crossing over at the sites of chiasmata. These pairs are also called bivalents or tetrads Prophase I of meiosis 28

29 What is the consequence of crossing over? Metaphase I of meiosis Bivalents are organized along the metaphase plate Pairs of sister chromatids are aligned in a double row, rather than a single row (as in mitosis) The arrangement is random with regards to the (blue and red) homologues A pair of sister chromatids is linked to one of the pole And the homologous pair is linked to the opposite pole 29

30 Metaphase, Anaphase and Telophase of Meiosis I How many chromosomes? How many genomes? What is the DNA content? Meiosis II: in fact a mitosis Meiosis I is followed by cytokinesis and then meiosis II The sorting events that occur during meiosis II are similar to those that occur during mitosis However the starting point is different For a diploid organism with six chromosomes (2n=6) Mitosis begins with 12 chromatids joined as six pairs of sister chromatids. i.e. 3 pairs of chromosomes (2n); each chromosome containing 2 chromatids. Meiosis II begins with 6 chromatids joined as three pairs of sister chromatids. i.e. 3 chromosomes (1n); each chromosome containing 2 chromatids. 30

31 Meiosis II Meiosis summary for 2n=2 Start with 1 cell (2 chromosomes, 2 chromatids (not shown)) DNA replicates during S phase (2 chromosomes, 4 chromatids) Homologous pairs line up at metaphase (2 chromosomes, 4 chromatids) Homologous pairs separate at Anaphase I (2 chromosomes, 4 chromatids) After Telophase I and Cytokinesis, 2 daughter cells (1 chromosome, 2 chromatids) After Telophase II and Cytokinesis, 4 daughter cells (1 chromosome, 1 chromatid) 31

32 What is consequence of independent assortment of chromosomes? So why are YOU so different from mom and dad??? Two meiotic reasons Crossing over at Prophase I Independent assortment of chromosomes at anaphase I BOTH are forms of recombination 32

33 Crossing over and independent assortment are happening in the same meiosis Crossing over happens because homologs pair in meiosis I Independent assortment happens because the chromosomes segregate randomly at anaphase I after their random alignment at metaphase I and when you put them together in, say, a human context? 23 pairs of chromosomes, aligning on the metaphase plate independently of each other and segregating during the subsequent anaphase well there s a formula: 2 n where n = # chromosome pairs Plug in the numbers and you get well millions of possible combinations Add in recombination and, well.is it any wonder you re different from mom and dad? What s another ENORMOUS consequence of this variability? 33

34 Differences between meiosis and mitosis 1) Mitosis forms two identical daughters; meiosis forms four gametes that are not identical. 2) Meiotic Prophase I: Crossing over occurs, forming recombinant chromosomes. 3) Meiotic Interphase II: No DNA replication. 4) Prophase is considerably lengthened, relative to mitosis. In mammalian females, prophase begins in gestation and continues until the oocyte grows during an estrous or menstrual cycle. 34

35 35

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