aula 2 2023-24

Prévia do material em texto

<p>1</p><p>Genética e assuntos humanos: porquê estudar genética?</p><p>A descoberta da natureza do material genético: requisitos do material</p><p>genético; Evidências diretas e indiretas da natureza do material genético;</p><p>Nucleótidos como unidade básica dos ácidos nucleicos; O modelo de</p><p>Watson e Crick e outras formas de DNA.</p><p>Organismos-modelo em genética.</p><p>Genetics and human affairs: why learn genetics?</p><p>The discovery of the nature of genetic material: Requirements of the</p><p>genetic material; Direct and indirect evidence of the nature of genetic</p><p>material; Nucleotides as the basic unit of nucleic acids; The Watson-Crick</p><p>model and other forms of DNA.</p><p>Model organisms in genetics.</p><p>1</p><p>GENÉTICA 40308 | GENETICS 40308</p><p>AULA 1 | LESSON 1</p><p>Genetics and human affairs</p><p>• Questions on heredity are not exclusive to</p><p>modern times</p><p>– How far can we trace this topic?</p><p>2</p><p>2</p><p>Genetics and human affairs</p><p>• Health</p><p>• Evolution, biodiversity and conservation</p><p>• Agriculture and food supply</p><p>• Ethics</p><p>• Society and citizenship</p><p>4</p><p>The transformative power of genetic literacy</p><p>Blame it on heredity:</p><p>it’s in our DNA</p><p>6</p><p>1953 - James Watson and Francis Crick discover the double helix structure of DNA</p><p>3</p><p>Sort chronologically</p><p>7</p><p>• nuclein is discovered (Miescher)</p><p>• DNA is the transforming principle (Avery, Avery, McLeod and McCarthy)</p><p>• gene is the unit of heredity (Bateson)</p><p>• the pattern of X-ray difraction of DNA (Wilkins and Franklin)</p><p>• the chemical composition of nucleotides (Levene)</p><p>• DNA is the molecule that contains genetic information (Hershey and Chase)</p><p>• there is a regular proportion of nucleotides (Chargaff)</p><p>• some proteins contein a-helices (Pauling)</p><p>• the transforming principle is thermo-stable (Griffiths)</p><p>5 minutes</p><p>The nature of genetic material</p><p>Miescher discovers nuclein1869</p><p>Nuclein is isolated from</p><p>sperm of fish and from blood</p><p>cells</p><p>4</p><p>Miescher discovers nuclein1869</p><p>Rediscovers the work of Mendel</p><p>and uses the expression gene for</p><p>the first time, as well as the</p><p>terms homozygous and</p><p>heterozygous</p><p>William Bateson: uses the term gene1902</p><p>The nature of genetic material</p><p>Miescher discovers nuclein1869</p><p>William Bateson: uses the term gene1902</p><p>The nature of genetic material</p><p>Levene: nucleotides are the basic units of DNA1919</p><p>Nucleotides contain a nitrogen</p><p>base, a sugar molecule and a</p><p>phosphate group</p><p>5</p><p>Griffith discovers the “transforming principle”1928</p><p>The transforming principle is</p><p>not inactivated when</p><p>Streptococcus pneumoniae</p><p>cells are killed by heat.</p><p>Miescher discovers nuclein1869</p><p>William Bateson: uses the term gene1902</p><p>The nature of genetic material</p><p>Levene: nucleotides are the basic units of DNA1919</p><p>6</p><p>13</p><p>Griffith discovers the “transforming principle”1928</p><p>Miescher discovers nuclein1869</p><p>William Bateson: uses the term gene1902</p><p>The are equal amounts of A</p><p>and T as well as C and G but</p><p>the the proportion of G+C is</p><p>variable among species</p><p>The nature of genetic material</p><p>Levene: nucleotides are the basic units of DNA1919</p><p>Chargaff observed equal proportions of some nucleotides1940s</p><p>7</p><p>Griffith discovers the “transforming principle”1928</p><p>Miescher discovers nuclein1869</p><p>William Bateson: uses the term gene1902</p><p>The nature of genetic material</p><p>Levene: nucleotides are the basic units of DNA1919</p><p>Chargaff observed equal proportions of some nucleotides1940s</p><p>Avery, MacLeod and McCarthy: DNA is the “transforming principle”1944</p><p>Selective removal od</p><p>components of the extract</p><p>8</p><p>Griffith discovers the “transforming principle”1928</p><p>Miescher discovers nuclein1869</p><p>William Bateson: uses the term gene1902</p><p>The nature of genetic material</p><p>Levene: nucleotides are the basic units of DNA1919</p><p>Chargaff observed equal proportions of some nucleotides1940s</p><p>Avery, MacLeod and McCarthy: DNA is the “transforming principle”1944</p><p>Pauling discovers the a-helix in proteins1948</p><p>Analysis of the structure of</p><p>proteins by crystallography</p><p>Griffith discovers the “transforming principle”1928</p><p>Miescher discovers nuclein1869</p><p>William Bateson: uses the term gene1902</p><p>The nature of genetic material</p><p>Levene: nucleotides are the basic units of DNA1919</p><p>Chargaff observed equal proportions of some nucleotides1940s</p><p>Avery, MacLeod and McCarthy: DNA is the “transforming principle”1944</p><p>Pauling discovers the a-helix in proteins1948</p><p>Experiments with Escherichia</p><p>coli and bacteriophage T2</p><p>Alfred Hershey and Martha Chase: DNA is the genetic material1952</p><p>9</p><p>“The blender experiments”</p><p>Griffith discovers the “transforming principle”1928</p><p>Miescher discovers nuclein1869</p><p>William Bateson: uses the term gene1902</p><p>The nature of genetic material</p><p>Levene: nucleotides are the basic units of DNA1919</p><p>Chargaff observed equal proportions of some nucleotides1940s</p><p>Avery, MacLeod and McCarthy: DNA is the “transforming principle”1944</p><p>Pauling discovers the a-helix in proteins1948</p><p>Hershey and Chase: DNA is the genetic material1952</p><p>Wilkins and Franklin: DNA is an helix 1952</p><p>The pattern of X-ray</p><p>difraction of DNA</p><p>corresponds to an helix</p><p>10</p><p>“photo 51”</p><p>Watson e Crick:</p><p>making sense of available evidence</p><p>11</p><p>DNA structure</p><p>Two nucleotide</p><p>antiparallel chains:</p><p>the phosphate group</p><p>binds to the 3‘</p><p>carbon of one</p><p>deoxyribose and to</p><p>the 5' carbon of the</p><p>next giving polarity</p><p>to the chain.</p><p>The bases are linked</p><p>to carbon 1 of each</p><p>deoxyribose.</p><p>The bases are</p><p>connected by</p><p>hydrogen bonds,</p><p>keeping the two</p><p>nucleotide chains</p><p>together.</p><p>The backbone of each</p><p>nucleotide chain is a</p><p>polymer of phosphate</p><p>and deoxyribose units</p><p>joined by phosphodiester</p><p>bonds.</p><p>Griffiths et al., 1999</p><p>The helical structure results from the pairing of the bases:</p><p>the bases are flat structures that stack in a compact way by</p><p>excluding the water molecules that occupy the spaces</p><p>between them.</p><p>The helical conformation corresponds to the greater</p><p>stability of the molecule: it gives rise to the formation of a</p><p>major groove and a minor groove.</p><p>One complete revolution of the double helix corresponds to</p><p>10 base pairs (34Å ~ 3.4 nm).</p><p>Although hydrogen bonds are weak bonds, the two</p><p>nucleotide chains are held together by a very high number</p><p>of these bonds.</p><p>Griffiths et al., 1999</p><p>12</p><p>The structure of DNA meets the</p><p>requirements of genetic material</p><p>• It contains information</p><p>• It is faithfully duplicated</p><p>• It is stable but not immutable</p><p>Developments of the model</p><p>• Is the Watson & Crick model universal?</p><p>• Are all DNAs alike?</p><p>13</p><p>Developments of the model</p><p>• Is the Watson & Crick model universal?</p><p>• Are all DNAs alike?</p><p>• The hydration level</p><p>• Salt concentration</p><p>• DNA sequence</p><p>• Quantity and direction of</p><p>supercoiling</p><p>• Presence of modified</p><p>bases</p><p>• Presence of metal ions,</p><p>polyamines in the solution</p><p>Developments of the model</p><p>A-DNA</p><p>right-handed</p><p>shorter and wider</p><p>helical structure,</p><p>found in dehydrated</p><p>DNA samples.</p><p>Z-DNA</p><p>left-handed helical</p><p>structure; it is a</p><p>transient form in</p><p>certain types of</p><p>biological activity.</p><p>14</p><p>Developments of the model</p><p>• Rare forms of DNA</p><p>10 bp11 bp</p><p>12 bp</p><p>9.33 bp 8 bp</p><p>Model organisms in genetics</p><p>• Molecular genetics</p><p>• Transmission genetics</p><p>• Population genetics</p><p>15</p><p>Organismos-modelo em genética</p><p>“Anything found to be true of E. coli must also</p><p>be true of elephants” Jacob & Monod, 1963</p><p>31</p><p>• Small dimensions and ease of maintenance in the laboratory</p><p>• Short generation time</p><p>• Small genome</p><p>• Easy to cross in the lab</p><p>• Numerous offspring</p><p>32</p><p>16</p><p>Virus Phage T4</p><p>Cellular</p><p>organisms</p><p>Prokaryotes Escherichia coli</p><p>Eukaryotes</p><p>Unicellular Sacharomyces</p><p>cerevisiae</p><p>Mycelial Neurospora</p><p>crassa</p><p>Multicellelular</p><p>Plants Arabidopsis</p><p>thaliana</p><p>Animals</p><p>Invertebrates</p><p>Hermaphrodite Chaenorabditis</p><p>elegans</p><p>Non-</p><p>hermaphrodite</p><p>Drosophila</p><p>melanogaster</p><p>Vertebrates Mus musculos</p><p>33</p><p>Escherichia coli</p><p>Simple nutritional requirements | Rapid growth | Well-known genetics | Genotypic and phenotypic diversity</p><p>17</p><p>Escherichia coli</p><p>Simple nutritional requirements | Rapid growth | Well-known genetics | Genotypic and phenotypic diversity</p><p>Lederberg & Tatum, 1946 Hershey & Chase, 1952 Meselson & Stahl, 1958</p><p>Bacterial conjugation DNA contains</p><p>information Semi-conservative replication</p><p>Neurospora crassa</p><p>Prototrophic | Haploid | Sexual and asexual reproduction | Sexual types | Ordered ascospores</p><p>Ordered octade analysis and</p><p>recombination mapping</p><p>18</p><p>Neurospora crassa</p><p>Prototrophic | Haploid | Sexual and asexual reproduction | Sexual types | Ordered ascospores</p><p>Beadle & Tatum, 1941</p><p>A gene-an enzyme</p><p>Sacharomyces cerevisae</p><p>Unicellular | Sexual and asexual reproduction | Sexual types</p><p>19</p><p>Sacharomyces cerevisae</p><p>Unicellular | Sexual and asexual reproduction | Sexual types</p><p>Hartwell, Hunt & Nurse, 2001</p><p>Cell cycle regulation</p><p>Drosophila melanogaster</p><p>Simple nutritional requirements | Rapid growth | Eukaryote with small genome| Phenotypic diversity</p><p>20</p><p>Drosophila melanogaster</p><p>Simple nutritional requirements | Rapid growth | Eukaryote with small genome| Phenotypic diversity</p><p>Morgan, 1910 Sturtevant, 1911</p><p>Genes and chromosomes Gene linkage</p><p>Arabidopsis thaliana</p><p>Plant (Brassicaceae) | Small size| Short life cycle | Small genome</p><p>21</p><p>Arabidopsis thaliana</p><p>Plant (Brassicaceae) | Small size| Short life cycle | Small genome</p><p>The Arabidopsis Genome</p><p>Initiative, 2000</p><p>First plant with sequenced genome</p><p>• Genetic regulation of</p><p>development</p><p>• Mutation</p><p>• Genetic regulation of</p><p>physiology and pathogenesis</p><p>• Genetic mechanisms of</p><p>disease resistance and</p><p>environmental stress</p><p>•</p><p>Caenorhabditis elegans</p><p>Multicellular | Transparent body| Small size | Small genome | XX - hermaphrodite</p><p>22</p><p>Caenorhabditis elegans</p><p>Multicellular | Transparent body| Small size | Small genome | XX - hermaphrodite</p><p>• Genetic regulation of</p><p>development</p><p>• Apoptosis</p><p>• Genetic regulation of the</p><p>nervous system</p><p>• Genetic basis of behavior</p><p>Mus musculus</p><p>Multicellular | Vertebrate | Small size | Numerous offspring | Short life cycle</p><p>23</p><p>Mus musculus</p><p>Multicellular | Vertebrate | Small size | Numerous offspring | Short life cycle</p><p>• Genetic engineering</p><p>• Genetic basis of human</p><p>diseases (murine model)</p><p>• Cancer and anti-tumor</p><p>therapy</p><p>• Regulation of embryonic</p><p>development in mammals</p><p>Pre-mendelian theories:</p><p>blending inheritance</p><p>Pre-mendelian</p><p>Mixture of fluids,</p><p>vapours, particles,</p><p>gemmules</p><p>Mendelian</p><p>Inheritable traits as</p><p>transmitted as discrete</p><p>factors</p><p>48</p>