Genetics Lesson 3-4 PDF

Biomedical Sciences & Therapeutics: Genetics (MSOP-1002)  Lectures 3-4 contents Mendel vs Darwin ‘Modern’ evolution The link between Mendelian and Darwinian theories Link between chromosomes and heredity Cell cycle and cell division Mitosis and meiosis (and the difference)...

Biomedical Sciences & Therapeutics: Genetics (MSOP-1002)  Lectures 3-4 contents Mendel vs Darwin ‘Modern’ evolution The link between Mendelian and Darwinian theories Link between chromosomes and heredity Cell cycle and cell division Mitosis and meiosis (and the difference) Chromosome structure and function  Mendel vs Darwin There is no evidence that Darwin knew about Mendel’s experiments, and he certainly didn’t cite his work in his own publications However Mendel did know of Darwin’s studies and was critical of some ideas For example, Darwin wrote a ‘provisional hypothesis for Pangenesis’ in which each organ or tissue had ‘gemmules’ which had trait information These gemmules travelled via the circulatory system to the reproductive organs and parental gemmules combined at fertilization  ‘Modern’ natural selection During the industrial revolution, pollution changed the city environment rapidly and significantly Prior to 1848, all examples of the Peppered Moth collected were grey/white with black mottling. In 1848 a black variant (carbonaria) found in Manchester By 1900, 90% city peppered moths were carbonaria Thus moths that had the beneficial colour trait had a greater probability of surviving to reproduce, thus leading to a population density increase in that trait - natural selection!  ‘Modern’ natural selection In the 1950’s, Bernhard Kettlewell conducted ‘mark/ release/ recapture’ experiments, showing higher bird predation of moths in non-camoflaged environments (city and country) Remember such new variants occur by RANDOM mutation ‘Modern’ natural selection Individuals of one extreme phenotype are favoured Numbers of phenotype vary in population  Paleontology Paleontology is the study of of the history and development of life on earth This is primarily based on the fossil record. Fossils are generally the mineralised remains (e.g. skeletal) or traces (e.g. footprints) of living organisms in rock or sediments The geological position of fossils enables dating and the examination of remains enables evolutionary relationships to be determined, and phylogenetic trees drawn (phylon – tribe or race, genesis – birth) As new fossil finds are discovered, continued clarification of how species have evolved (or died out)  Evidence for Evolution: Fossils Fossil records show – Extinctions – Change in species 17  Common ancestry Natural Selection envisages the origins of species currently living on earth form a ‘tree’ Thus different modern species have common ancestors The common ancestor of man and apes is known as the ‘missing link’: this would be neither human nor ape Natural selection and genetic transmission Despite the robustness of Darwin’s theory, it was not based on Mendel’s ideas of genetic transmission Indeed, seven years after (1866) the Origin of Species was published, Mendel stated ‘the laws of inheritance are for the most part unknown’ On the surface, Darwin believed in ‘continuous variation’ and Mendel in ‘discontinuous variation’ Natural selection and genetic transmission Darwin died in 1882, and Mendel in 1884. Around this time, several scientists noted so-called ‘coloured bodies’ or ‘chromosomes’ in nuclei of stained cells The German anatomist Walther Flemming described the segregation of chromosomes into daughter cells during cell division. He called the process ‘mitosis’ (Greek for thread)  Linking Mendel and Darwin In 1900, the Englishman William Bateson became pre-eminent in ‘rediscovering’ and popularising Mendel and invented the term ‘genetics’ After confirming Mendel’s data, the botanist Hugo DeVries postulated a ‘mutation theory’ to explain evolution. He also coined the term ‘pangene’ for the unit of inheritance, from Darwin’s - pangenesis (‘whole’ ‘origin’) – theory of heredity  Linking Mendel and Darwin With Mendel’s work in higher profile, Boveri & Sutton were first to link chromosome behaviour in cell division to Mendelian segregation in 1902 In 1911, American Thomas Hunt Morgan linked Mendelian inheritance to (sex) chromosomes in studies with fruit flies displaying mutant traits He also proposed the idea of ‘genetic linkage’ where he observed some traits were often inherited together  Linking Mendel and Darwin Thus the process of heredity involves both the orderly transmission of Mendel’s ‘particulate factors’ (i.e. genes/chromosomes) and ‘natural selection’ based on smaller genetic changes (e.g. mutations) producing slight variations in the population, which may confer survival or reproductive advantage  Genes Are on Chromosomes Mendel was unaware of chromosomes – “Genes” were inheritable units – Their physical structure was unknown Chromosomes seen to segregate during mitosis (Flemming) ‘Chromosome theory of inheritance’ (Boveri & Sutton) – Inherited units (genes) are on the chromosomes Essential Cell Biology (© Garland Science 2010)  How Are Chromosomes, DNA, and Genes Related? Homologous chromosomes – Chromosomes that pair up during meiosis – Contain the same genes – One comes from each parent Each is one long DNA molecule – A gene is a short region of the molecule – Each chromosome can have > 1,000 genes Somatic Cells are Diploid  Karyotype Chromosomes are visible during mitosis Humans have 46 chromosomes Sex chromosomes Females have 2 X chromosomes (XX) Males have X and Y (XY) Autosomes The other 22 pairs of chromosomes are homologous  Homologous Chromosomes 46 chromosomes are arranged in 23 pairs – One came from each parent 22 pairs are autosomes – Both chromosomes are homologues 1 pair are sex chromosomes – Can be homologous; XX for females – Can be different; XY for males © 2009 W.W. Norton & 22 Company, Inc. Homologous Chromosomes  Cell Division When eukaryotic (e.g. human), somatic cells divide, the whole process is called Mitosis When ‘germ’ cells divide (producing gametes) it is known as Meiosis Cell division (confusingly also known as mitosis) is only one part of the ‘cell cycle’ Most of the cell cycle is called Interphase – this is where cell prepares for cell division (DNA replication → sister chromatids) In mitosis chromatids spilt at centromere → identical chromosomes → each migrates in a new ‘daughter cell’ The Cell Cycle Interphase: The Longest Stage The period between divisions – Longest phase of the cell cycle – The cell prepares to divide Divided into 3 stages: – G1: growth after mitosis (M phase) – S: synthesis of DNA – G2: growth before mitosis (M)  G1 and G2 phases G stands for “gap” – Early biologists saw a gap Between S phase and cell division – Important for two reasons periods of growth – size of cell and protein content increase preparation for next phase – checkpoint that ensures conditions are suitable  G0 Phase Most cells are not actively dividing These cells are in G0 phase – Can last days to years – Some cells will divide again; e.g. liver cells – Some cells stay in G0; e.g. nerve cells  Mitosis Consists of five phases – Prophase – (Prometaphase) – Metaphase – Anaphase – Telophase Cytokinesis: division of the cytoplasm Mitosis  Prophase Cell enters mitosis – Chromosomes condense – Centrosomes move apart Go to the poles of the cell – Mitotic spindle begins to form  Prometaphase Mitosis proceeds – Chromosome condensation completed – Nuclear envelope breaks down – Mitotic spindle extends from centrosomes Attaches to centromeres of chromosomes Kinetochore: site of attachment Chromatids linked to opposite poles  Metaphase Chromosomes line up – Metaphase plate – Align sister chromatids Equal and balanced segregation  Anaphase Chromatids separate – Break free and dragged to opposite sides Microtubules shorten Result: – Equal segregation of chromosomes in two daughter cells  Telophase and Cytokinesis Telophase: – Chromosomes reach the poles – Mitotic spindle falls apart – Chromosomes unfold – Nuclear membrane reforms Cytokinesis – Cytoplasm is divided – Two cells are formed  Meiosis Used to make gametes Meiosis – Ovules/eggs and pollen/sperm Chromosome number is halved (haploid) Zygote is diploid after fertilisation Fertilization Mitosis  Meiosis vs Mitosis Meiosis is the process of cell division that occurs in ‘germ’ (from germinate) cells (gametes; eggs, sperm) The process of meiosis is essentially the same as for mitosis, except with a crucial, extra ‘reductional’ cell division producing 4 daughter cells from each parent cell The resulting daughter cells are thus haploid – only one set of chromosomes, from one parent only In mitosis the daughter cells are diploid – two sets of chromosomes, one originating from each parent During fertilisation, gametes combine to reconstitute diploid zygotes  Meiosis I vs. Mitosis Sister Chromatids separate Sister Chromatids remain attached Make notes to compare and contrast events in Mitosis vs Meiosis I  Meiosis II Metaphase Anaphase  Meiosis vs Mitosis In meiosis, homologous chromosomes (e.g. #3 – one from each parent) pair up during prophase I on the spindle – this pairing does not happen in mitosis These pairs align along the length of the chromatids and ‘zip’ together in ‘synapsis’ At this stage the pair exchange homologous parts in a process called ‘crossing-over’ (first noted by Morgan in 1916)  Meiosis vs Mitosis This is another system, like independent assortment (of whole chromosomes) in gamete production, that results in an increase in genetic variation within a population Thus genes that are closely positioned often result in linked traits in individuals – genetic linkage The new combination of traits may prove to be advantageous (or not) to survival and reproduction – a major contributor to Natural Selection  Linkage and Crossing Over Linkage: 2 genes on the same chromosome – Not independently assorted – Segregate together Crossing over – Linked genes should segregate together – Crossing over causes them to separate Crossing Over Reduces Genetic Linkage Homologous chromosomes line up during metaphase of meiosis Parts of maternal and paternal chromosomes migrate Linked Genes Are Inherited Together ◼ Test cross ◼ Independent assortment predicts ¼ of each phenotype ◼ Results are much different ◼ These genes are linked 8 Impact of Crossing Over Linked genes should always assort together Should have resulted in two phenotypes – Both recessive or both dominant traits – 50% of each Crossing over changes that result – Result is less clear-cut 9  Chromosomes Package DNA DNA molecules are enormously long – Double helix nearly 2 metres in length DNA is tightly packaged with proteins Chromatin – DNA and proteins Chromosome – Tightly packed  Chromosomes and DNA The strand of DNA is wrapped round structures called nucleosomes Nucleosomes consist of proteins called histones, arranged into ‘beads’ Each bead has a precise length of DNA wrapped round it The string of nucleosomes is called chromatin Mutiple chromatin strings fold into fibres The chromatin fibres form loops which pack into the chromatids (chromosome arms) Electron microscope image of chromatin (nucelosomes visible) Levels of Packaging Metaphase—fully condensed Tightly packed loops 30 nm fibers Histone spool Double helix  Managed Student Centred Learning (MSCL) Read relevant sections in Chapters 9,10, 12 and 13 in ‘Discover Biology’ (Cain et al) core module textbook Try some of the ‘Self-Quiz’ questions (at end of chapters) for topics we’ve covered Some animations placed on Moodle Remember to listen to BBC Sounds link: ‘In Our Time: mutation, evolution & disease’ on Moodle Relevant weblinks on Moodle (e.g. ‘What Darwin didn’t know’ article)