Introduction To Medical Biology PDF

Introduction to the Molecular Cell Biology Dr. Selma Yılmaz Department of Medical Biology BOOKS: Lodish, Weaver,...

Introduction to the Molecular Cell Biology Dr. Selma Yılmaz Department of Medical Biology BOOKS: Lodish, Weaver, Lippincott, Alberts Molecular Cell Biology Garden pea flowers. Flower color (purple or white) was one of the traits Mendel studied in his classic examination of inheritance in the pea plant.  LIFE BEGINS WITH CELLS q Molecular Cell Biology, is a rich , integrative sicience that brings together biochemistry, biophysics, molecular biology, microscopy, genetics, physiology, computer science and developmental biology. q Each of these fields has its own ephasis and style of experimentation. q We will describe insights and experimental approaches from all of these fields, gradually weaving the multifaceted story of the birth, life and death of the cells. q We will start by introducing the unity and diversity of the cells, their contituents and critical functions, and what we can learn by studying the cells.  LIFE BEGINS WITH CELLS Figure 1-13 Simulated cross section of an E. coli cell magnified around one millionfold. Voet Figure 1-4 Phylogenetic tree. Voet Figure 1-14 Example of the hierarchical Figure 1-11 organization of Evolutionary biological tree structures. Voet indicating the lines of descent of cellular life on Earth.Voet Life defines these, what The Cells do? Order Response to the environment Evolutionary adaptation Regulation Reproduction Energy processing Growth and development  LIFE BEGINS WITH CELLS Like ourselves, the individual cells that form our bodies can grow, reproduce, process information respond to stimuli, carry out an amazing array of chemical reactions. These abilities define life. qWe and otherorganisms contain billions or trillions of cells organized into complex structure, but many organisms consist of a single cell. q Even simple unicellular (single-celled) organisms exhibit all the hallmark properties of life, indicating that the cell is the fundemental unit of life. q As twenty-first century opens, we face an explosion of new data about the components of the cells, what structures they contain, how they influence each other. q Still, an immense amount remains to be learned, particularly how information flow through cells and how they decide on the most appropriate ways to respond.  LIFE BEGINS WITH CELLS The meaning of being alive is not just order, organization and complexity. More importantly, it is the ability to create, to get organized, to insure organization in a hostile environment working against it. In a way, creation of a new life is miraculous. In order to create order, a plan is necessary. Cells get organized by following a pre-existing plan." First of all a plan and then a will (management) to execute this plan is needed so that objects are in order in a space. And a compelling energy is required from inside and outside so that the living system is steady.  FOCUS ON THE CELL What are the cells? q All living creatures are made of cells. q Cells are small membrane-bounded compartments filled with a concentrated aqueous solution of chemicals. q The simplest forms of life are solitary cells that Figure 1. Transport propagate by dividing in two. proteins in the cell q Higher organisms, such as ourselves, are like cellular membrane cities in which groups of cells perform specialized A plasma membrane is permeable to specific functions and are linked by intricate systems of molecules that a communication. cell needs. Transport proteins What do we want to learn from cells? in the cell membrane allow for We study cells to learn: selective passage of specific q How they are made from molecules and molecules from the external environment. Each transport q How they cooperate to make an organism as protein is specific to a certian complex as a human being. molecule (indicated by matching colors). © 2010 Nature Education What is cells? Modern Cell Theory q All known living things are made up of cells. q The cell is structural & functional unit of all living things. q Cells come from pre-existing cells by division. The simplest forms of life are solitary cells that propagate by dividing in two. Figure 1. Transport q Cells contains hereditary information (DNA) which is proteins in the cell passed from cell to cell during cell division. membrane q Cells are small membrane-bounded compartments A plasma membrane is permeable to specific filled with a concentrated aqueous solution of chemicals molecules that a and are basically the same in chemical composition cell needs. Transport proteins (composed of just six elements: C,H,O,N,P,S) in the cell membrane allow q Energy flow (metabolism & biochemistry) of life for selective passage of specific occurs within cells. molecules from the external qHigher organisms, such as ourselves, are like cellular environment. Each transport cities in which groups of cells perform specialized protein is specific to a certian functions and are linked by intricate systems of molecule (indicated by matching colors). communication. © 2010 Nature Education  WHAT MAJOR COMPONENTS DO CELLS HAVE? -Water (H2O): ) is the most abundant molecule in cells (70% or more of total cell mass). Cells are composed of water, inorganic ions, and carbon-containing Organic molecules. -Nucleic acids : deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). -Proteins -Carbohydrates -Complex carbohydrates -Lipids or fat molecules - Organelles: Some cells also feature orderly arrangements of molecules called organelles. One example is the mitochondrion in animals (chloroplasts in plants) — commonly known as the cell's "power plant" — which is the organelle that Fgur 2. The composition of a bacterial cell. Most of a cell is water (70%). The remaining 30% holds and maintains the machinery involved contains varying proportions of structural and in energy-producing chemical reactions. functional molecules. © 2010 Nature Education  WHAT ARE THE DIFFERENT CATEGORIES OF CELLS? Rather than grouping cells by their size or shape, scientists typically categorize them by how their genetic material is packaged. If the DNA within a cell is not separated from the cytoplasm, then that cell is a prokaryote. All known prokaryotes, such as bacteria and archaea, are single cells. In contrast, if the DNA is partitioned off in its own membrane-bound room called the nucleus, then that cell is a eukaryote. Some eukaryotes, like amoebae, are free-living, single-celled entities. Other eukaryotic cells are part of multicellular organisms. For instance, all plants and animals are made of eukaryotic cells — sometimes even trillions of them. Figure 4: Comparing basic eukaryotic and prokaryotic differences A eukaryotic cell (left) has membrane-enclosed DNA, which forms a structure called the nucleus (located at center of the eukaryotic cell; note the purple DNA enclosed in the pink nucleus). A typical eukaryotic cell also has additional membrane-bound organelles of varying shapes and sizes. In contrast, a prokaryotic cell (right) does not have membrane-bound DNA and also lacks other membrane- bound organelles as well. © 2010 Nature Education  HOW DID CELLS ORIGINATE? Living organisms are structurally different and inside all living cells – cells are different as those of bacteria, or flies, or frogs and humans and those of skin, liver, and brain – are the same or nearly the same molecules and interactions, that make life work. We are led to think twin conclusions: – The basic structure and mechanisms that sustain life on earth today are common to all living creatures; and – The processes that have created life as we know it have been guided by a common set of rules. Thus, all forms of life are connected to one another and their predecessors _ all the way back to what was most probably a single beginning almost 4 billion years ago. HOW DID CELLS ORIGINATE? Researchers hypothesize that all organisms on Earth today originated from a single cell that existed some 4 billion years ago. This original cell was likely little more than a sac of small organic molecules and RNA-like material that had both informational and catalytic functions. Over time, the more stable DNA molecule evolved to take over the information storage function, whereas proteins, with a greater variety of structures than nucleic acids, took over the catalytic functions. Then, according to some theories of cellular evolution, one of the early eukaryotic cells engulfed a prokaryote, and together the two cells formed a symbiotic relationship. Figure 5: The origin of mitochondria and chloroplasts Mitochondria and chloroplasts likely evolved from engulfed prokaryotes that once lived as independent organisms. At some point, a eukaryotic cell engulfed an aerobic prokaryote, which then formed an endosymbiotic relationship with the host eukaryote, gradually developing into a mitochondrion. Eukaryotic cells containing mitochondria then engulfed photosynthetic prokaryotes, which evolved to become specialized chloroplast organelles. © 2010 Nature Education The Evolution Of The Cell - Patterns All organisms, and all of the cells that constitute them, are believed to have descended from a common ancestor cell through evolution by natural selection. This involves two essential processes: (1) the occurrence of random variation in the genetic information passed from an individual to its descendants and (2) selection in favor of genetic information that helps its possessors to survive and propagate. Evolution is the central principle of biology, helping us to make sense of the bewildering variety in the living world.  A. From Molecules to the First Cells All cells are made from the same major classes of organic molecules. 1. Simple Biological Molecules Can Form Under Prebiotic Conditions: Most important, representatives of most of the major classes of small organic molecules found in cells are generated, including amino acids, sugars, and the purines and pyrimidines required to make nucleotides. DNA, RNA, And Protein Are Composed Of Just Six Elements: Hydrogen, Carbon, Nitrogen, Oxygen, Sulfur, Phosphorus 2. Simple Organic Molecules Such As Amino Acids And Nucleotides Can Associate To Form Polimers. Polypeptides (proteins), polynucleotides (DNA and RNA), polysaccharides (carbohydrates) 3.. Polynucleotides Are Capable Of Directing Their Own Synthesis 4. Self-replicating Molecules Undergo Natural Selection 5. Specialized RNA molecules Can Catalyze Biochemical Reactions 6. Information Flows from Polynucleotides To Polypeptides 7. Membranes Defined the First Cell. Formation Of Cell Membranes: The structure and function of cells are critically dependent on membranes. The fundamental building blocks of all cell membranes are phospholipids. 8. All Present- Day Cells Use DNA as Their Hereditary Material  From Molecules to the First Cells Friedrich 1. Simple Biological Molecules Can Form Under Wöhler (1800- 1882), Chemist, Prebiotic Conditions best known for his synthesis of urea Likewise, both nucleotids and amino acids can be produced. A typical experiment simulating conditions on the primitive earth. A few of the Wohler experiment compounds that might form in the experiment (1828). described in Figure. Water is heated in a closed apparatus containing CH4, NH3, and H2, and an electric discharge is passed through the vaporized mixture. Organic compounds accumulate in the U-tube trap.  From Molecules to the First Cells 2. Simple Organic Molecules Such As Amino Acids And Nucleotides Can Associate To Form Polimers (random lenght and sequence). Formation of polynucleotides and polypeptides. Nucleotides of four kinds (here represented by the single letters. A, U, G, and C) can undergo spontaneous polymerization with the loss of water. The product is a mixture of polynucleotides that are random in length and sequence. Similarly, amino acids of different types, symbolized here by three-letter abbreviated names, can polymerize with one another to form polypeptides. Present-day proteins are built from a standard set of 20 types of amino acids. Like wise monosaccharides can polymerize with one another to form poly saccharides. 3. Polynucleotides Are Capable Of Directing Their Own Synthesis. Pairs of nucleotides (G with C and U with A) by relatively weak chemical bonds. 3. Polynucleotides Are Capable Of Directing Their Own Synthesis This pairing enables one polynucleotide to act as a template for the synthesis of another.  From Molecules to the First Cells 4. Self-replicating Molecules Conformation of an RNA molecule. Nucleotide pairing between different Undergo Natural Selection regions of the same polynucleotide (RNA) chain causes the molecule to adopt a distinctive shape. Alberts Mol Biol Cell. 5. Specialized RNA molecules Can Catalyze Biochemical Reactions. (Figure A, B) 6. Information Flows from Polynucleotides To Polypeptides. (Figure C). Evolutionary significance of cell- like compartments. Evolution of RNA molecules Conformation of an RNA molecule. Nucleotide pairing between different regions of the same polynucleotide (RNA) chain causes the molecule to adopt a distinctive shape. Alberts Mol Biol Cell. Suggested stages of evolution from simple self- replicating systems of RNA molecules to present- day cells. Today, DNA is the repository of genetic information and RNA acts largely as a go- between to direct protein synthesis. Alberts Mol Biol Cell.  From Molecules to the First Cells 7. Membranes Defined the First Cell. Formation Of Cell Membranes: The structure and function of cells are critically dependent on membranes. The fundamental building blocks of all cell membranes are phospholipids. Formation of cell membranes by phospholipids Phospholipids: At an oil-water interface: Because phospholipids have hydrophilic heads and lipophilic tails, they will align themselves at an oil-water interface with their heads in the water and their tails in the oil. In water: Phospholipids will associate to form closed bilayer vesicles in which the lipophilic tails are in contact with one another and the hydrophilic heads are exposed to the water. Life Needs an Inside and an Outside A. Cell Membrane=mouth, barier B. Larger ‘’Membranes’’ Bark Safeguards the living part of the trunk (usually the outermost ring) from insects, diseases, and harsh weather. The atmosphere helps regulate the earth’s temperature as it protects life from the sun’s harmful ultra-violet rays. C. HEADS OUT – TAILS IN When danger threatens musk oxen gather in a circle – heads and horns to the outside, tails to the inside –sheltering their vulnerable calves in the center. This circle of protection illustrates one of life’s most fundamental organizing principles __ a difference between in and out.  From Molecules to the First Cells 8. All Present- Day Cells Use DNA as Their Hereditary Material Molecular Biology of The Cell. Spiroplasma citrii, a mycoplasma that grows in plant cells. (Courtesy of Jeremy Burgess.). Unique among prokaryotes in that they lack a cell wall around their cell membrane and possess a three layered cellular membrane. Without a cell wall, they are unaffected by many common antibiotics such as penicillin. Alberts Mol Biol Cell.  B. From Prokaryotes to Eukaryotes qProkaryotic Cells Are Structurally Simple but Biochemically Diverse q Metabolic Reactions Evolve q Evolutionary Relationships Can Be Deduced by Comparing DNA Sequences q Cyanobacteria (also known as blue-green algae) Can Fix CO2 and N2 into Organic Molecules, qBacteria Can Carry Out the Aerobic Oxidation of Food Molecules qEukaryotic Cells Contain Several Distinctive Organelles q Eukaryotic Cells Depend on Mitochondria for Their Oxidative Metabolism qChloroplasts Are the Descendants of an Engulfed One protozoan eating another. Ciliates Prokaryotic Cell are single-cell animals that show an qEukaryotic Cells Contain a Rich Array of Internal amazing diversity of form and behavior. The top micrograph shows Membranes Didinium, a ciliated protozoan with two circumferential rings of motile cilia and a q Eukaryotic Cells Have a Cytoskeleton snoutlike protuberance at its leading q Protozoa Include the Most Complex Cells Known end, with which it captures its prey. In the bottom micrograph Didinium is q In Eukaryotic Cells the Genetic Material Is Packaged in shown engulfing another protozoan, Paramecium. Complex Ways (Courtesy of D. Barlow.)  How Cells Are Studied? A cell is the smallest unit of life. Most cells are so small that they cannot be viewed with the naked eye. Therefore, scientists must use microscopes to study cells. Electron microscopes provide higher magnification, higher resolution, and more detail than light microscopes. The unified cell theory states that all organisms are composed of one or more cells, the cell is the basic unit of life, and new cells arise from existing cells.  The Way Science Works ‘’ Science is, in essence, organized curiosity.’’ q Observation of and wonder at the workings of nature are what initiate ‘’why’’ questions. q These activities are not the sole province of scientists. q In fact, they begin in childhood and more or less developed in all of us. q We find observations of nature by novelists, poets, amateur scientists, and painters, done in their own ways. q Science joins art as another branch on the tree of observation and wonder.  Molecular Cell Biology Techniques An Ant by Scanning Electron MicroscopyEM A cell by Fluorescence microscopy Molecular cell Biology rapidly grew in the mid-20th century and it became possible to maintain, grow, and manipulate cells outside of living organisms. The study of cells at the molecular level was aided by: q Development of sterile cell culture techniques q The prior advances in electron microscopy, and q Later advances such as development of transfection methods, q Discovery of green fluorescent protein in jellyfish, and q Discovery of small interfering RNA (siRNA), among others. Using Microscopy R. Hooke discovered the to Explore the new world Using Cell and Beyond his Microscope -focus on the miniscule -Magnified to the max TOOLS OF SCIENCE -Comparing Sizes The cell’s nucleus. The nucleus is covered by outer and inner nuclear membranes (ONM Using A Scanning Electron and INM) and surrounded by cytoplasm, in Microscopy, A bacterial A 3_D interior. This view allows us towhich float various organelles. PM (plasma see many of the cell’s molecular DNA magnified using SEM. membrane) marks the double membrane structures, or organelles. that envelopes all of the cell’s contents. It’s a small world: A magnified pin point with a population of E.coli bacteria  TECHNIQUE RESULTS Light microscopy (a) Brightfield (unstained specimen) 50 µm (b) Brightfield (stained specimen) (c) Phase-contrast (d) Differential-interference- contrast (Nomarski) (e) Fluorescence 50 µm (f) Confocal 50 µm ‘’ Science is, in essence, organized TOOLS OF SCIENCE curiosity.’’ Not only Microscopy to Explore the Cell and Beyond, but others.. Using X-ray Diffraction , Light diffracted by DNA In this diffraction pattern of DNA T. Swedberg developed the captured by Rosalind Franklin and ultracentrifuge. ‘’Size, weight, deciphered by James Watson and density of a substance’’ This tiny Francis Crick, the distance between tissue section of liver cells, blood spots forming the X indicates the cells, and connective tissues distance between turns of the DNA’s would be ground up into helix. The X is a reliable indicator of a ‘’organic soup’’ and centrifuged helical (corkscrew-like) molecular shape. to separate out the various cellular components.  A Brief History of The Cell Late 1500’s – First lenses used in Europe 1595 – Zacharias Jansen - invented the first optical telescope and also the first truly compound microscope. 1655 –Robert Hooke - described the first “cells” cellula in cork (from the outer layer of the bark of the cork oak ) 1674 – Anton Leeuwenhoek - discovered first living cells in algae, free-living and parasitic microscopic protists, bacteria, sperm cells, blood cells, microscopic nematodes and rotifers, and much more. 1833 – Robert Brown- described the cell nucleus in cells of the orchid. 1838 – Mathias Schleiden - described that all plants are made of cells. 1839 - Matthias Schleiden and Theodor Schwann - formulated Cell theory. 1858- Rudolf Virchow - contributed to the Cell theory.  A Brief History of The Cell 1865- Gregor Johann Mendel - discovered herditary “factors” or ‘’units” (now is called genes)’’ and ‘’alleles’’, and the fundemental laws of Inheritance. 1869 - Friedrich Miescher - identified and isolated an acidic substance which he called ‘’nuclein’’ (now is called DNA) in the nuclei of white blood cells. 1879 –Walter Fleming, Strasburger, von Waldeyer-Hartz and Van Beneden laid the basis of cytology and cytogenetics; he found a structure, which he named chromatin. Chromatin was correlated to threadlike structures in the cell nucleus– the chromosomes; independently described chromosome behavior during mitosis, meiosis. 1898 – Golgi - described the golgi apparatus. 1902 – Walter Sutton and Theodor Boveri - independently developed the chromosome theory of inheritance.  A Brief History of The Cell 1915 – Thomas Morgan and his colleagues - published The Mechanism of Mendelian Heredity (integrated with the chromosome theory of inheritance): The Chromosomes Carry Genes. 1902- Archibald Garrod - discovered that a defective gene gives rise to a defective enzyme’ and prefigured “one gene- one enzyme”, also discovered alkaptonuria, understanding its inheritance. 1944 - Oswald Avery and his colleagues McLeod , McCarty - proved that genes are made of DNA. 1946 – Hermann Joseph Muller – discovered the physiological and genetic effects of radiation (mutagenesis) 1953-The double helix structure of DNA was first discovered by James Watson and Francis Crick, using experimental data collected by Rosalind Franklin and Maurice Wilkins. 1958- George Beadle and E. L. Tatum - proved that ’’a gene is responsible for the production of an enzyme’’...........  Cell Theory- Hans Jansen and son Zaccharias Jansen Late 1500’s – First lenses used in Europe to determine cloth quality (weave and precision), combos of lenses gave better view 1595 – Zacharias Jansen (1585-1632), a Dutch spectacle-maker : invention of the first optical telescope and also the first truly compound microscope. Jansen's microscope consisted of three draw tubes with lenses inserted into the ends of the flanking tubes. Zacharias Jansen (1585- 1632 Possible design of the first microscope  Cell Theory: Antonie van Leeuwenhoek 1674 – Anton Leeuwenhoek “the father of microbiology” discovered first living cells in algae in a drop of pond water using his handcrafted microscope. Named as animalcules (microscopic animals) (single-celled organisms –unicellular-, protists, now known as microorganisms) Algae Spirogyra Anton Leeuwenhoek discovered free-living and parasitic microscopic protists,(Protozoa the unicellular "animal-like such as flagellata; protophyta the "plant-like"(mostly unicellular algae); Molds the "fungus-like" (e.g.. slime molds and water molds), bacteria after A. Leeuwenhoek (1632 - years, sperm cells, blood cells, microscopic 1723)with his nematodes and rotifers, and much more. handcrafted microscope Some of his microscopic observations through correspondence with the Royal Society, which published his letters: muscle fibers, bacteria, spermatozoa, and blood flow in capillaries (small blood vessels).  Linneaus Biological Classification Today the system of classification When Carl Linnaeus developed his includes six kingdoms. biological classification (1735), there were only two kingdoms, Plants and The Six Kingdoms: Animals... Plants, Animals, Protists, Fungi, Carl von Linneaus When identifying an object, Linnaeus Archaebacteria, Eubacteria. (1707- 1778 ), first looked at whether it was animal, Swedish botanist, vegetable, or mineral. How are organism placed into their zoologist, and These three categories were the kingdoms? physician original domains. Domains were divided into kingdoms, · Cell type, complex or simple which were broken into phyla · Their ability to make food (singular: phylum) for animals and · The number of cells in their body divisions for plants and fungi. Phyla or divisions were broken into classes, which in turn were divided into orders, families, genera (singular: genus), and species. Species were divided into subspecies. In botany, species were divided into varietas (singular: variety) and forma (singular: form).  Cell Theory: Scleiden, Schwann, Virchow 1. All living things are made of one or more cells (1838-1839: Schleiden and Schwann) 2. The cell is the basic unit of life (1838-1839: Schleiden and Schwann). 3. Omnis cellula e cellula: All cells come from other cells (1858: Virchow). Theodor Schwann (1810-1882) Rudolf Virchow (1821-1902) Cell Theory for animals ‘’ all Cell Theory, Matthias Schleiden, animals are made of cells’’, "the father of modern pathology , (1804-1881) a German biologist, physiologist Anthropology, Social lawyer, botanist, Cell ‘the founder of modern Medicine, leukemia cells, Theory for plants ‘’all histology’’’, Schwann Cells, "Medicine is a social science, and plants are made of striated muscle (eusaphaugus), politics is nothing else but medicine cells’’ Pepsin enzyme on a large scale". The Origin of Species by Means of Natural Selection: ‘’all life is related and has descended from a common ancestor.’’ Each living creature must be looked at as a microcosm – a little universe formed of a host of self-propagating organisms, inconceivably minute and as numerous as the Alfred Russel Wallace (1823-1913) and stars in the heaven. Charles Darwin, 1856 Charles Darwin (1809-1882) 1858 - On the Tendency of Species to form Varieties; and on the Perpetuation of Varieties and Species by Natural Means of Selection, a joint presentation of two scientific papers to the Linnean Society of London. 1859 - Darwin published his book ‘’The Origin Of Species By Means Of Natural Selection’’ 1871 - Darwin wrote a warning about close relatives having children, buried in an obscure botanical textbook. Darwin's Galapágos finches demonstrate the priniciple of Darwin's study at Down House 'Survival of the Fittest'. Each has adapted to its environment.  Mendel s Laws of Inheritance 1865- Gregor Johann Mendel ”the Father of Genetics”: The hereditary “factors or units’’ (now called genes) A gene can exist in different forms “ alleles” Gregor Johann (alternative version of a gene) Mendel (1822 – 1884) Garden pea flowers. Flower color (purple or white) was one of the traits Mendel studied in his classic examination of inheritance in the pea plant. Dominant (red) and recessive (white) phenotypes. (1) Parental generation. (2) F1 generation, purple. Almost all purple (3) F2 generation, white in larger amount, consistenly in 1:3 ratio.  Molecular Genetics: What Genes are Made of or How They Work 1869 -The Discovery of DNA: Friedrich Miescher identified and isolated. Miescher discovered....‘’a mixture of compounds’’.. that he called ‘’nuclein’’ in the cell nucleus... vThe major component of ‘’nuclein’' is deoxyribonucleic acid (DNA). 1953-The double helix structure of DNA was first discovered by James Watson and Francis Crick, using experimental data collected by Rosalind Franklin and Maurice Wilkins.  1879-Walter Flemming (1843-1905): With the use of aniline dyes, he found a structure, which he named chromatin. Chromatin was correlated to threadlike structures in the cell nucleus– the chromosomes (meaning coloured bodies), Walther Flemming (1843 –1905), Physician, cell division, mitosis, chromatids Polytene (over-sized) chromosomes in a salivary gland cell. From Flemming's book Illustrations of cells with chromosomes and Zellsubstanz, Kern und Zelltheilung, 1885 mitosis, from the book Zellsubstanz, Kern und Zelltheilung, 1882 Thomas Morgan: The Chromosome Theory of Inheritance: The Mechanism of Mendelian Heredity A crucial new step in genetic thinking. Mendel’s theories was initially very controversial. 1910 - Thomas Morgan: provided the first Thomas Morgan definitive Evidence for the chromosome (1866 –1945), theory with the fruit fly (Drosophila Melanogaster) Nobel Prize for Medicine or 1915, Morgan and his colleagues published The Mechanism of Physiology in 1933 Mendelian Heredity. The Chromosome Theory of Inheritance: ‘’The Chromosomes Carry Genes’’ 1915- When Mendel's theories were integrated With the chromosome theory (the chromosomes carry the hereditary information—first suggested by Theodor Boveri and Walter Sutton) by Thomas Hunt Morgan, they became the core of classical genetics.  The Chromosome Theory of Inheritance: The Chromosomes Carry Genes Figure 1.Location of genes on chromosomes. (a) A schematic diagram of a chromosome, indicating the positions of three genes: A,B,and C. (b) A schematic diagram of a diploid pair of chromosomes, indicating the positions of the three genes —A, B, and C—on each, and the genotype (Aor a;Bor b; and Cor c) at each locus. Figure 2. Recombination in Drosophila. The two X chromo somes of the female are shown schematically. One of them (red) carries two wild-type genes: (m1), which results in normal wings, and ( w1), which gives red eyes. The other (blue) carries two mutant genes: miniature (m) and white (w). During egg formation, a recombination, or crossing over, indicated by the crossed lines, occurs between these two genes on the two chromosomes. The result is two recombinant chromosomes with mixtures of the two parental alleles. One is m1w, the other is m w1.  X-Ray Mutations Hermann J. Muller, geneticist and educator, best known for his work on the physiological and genetic effects of radiation (mutagenesis) on Drosophila. Muller frequently warned of long-term dangers of radioactive fallout from nuclear warand nuclear testing, which resulted in Hermann J. Muller (1890- 1967) greater public scrutiny of these practices. 1946 Nobel Prize in Physylogy and medicine. Lewis J. Stadler, geneticist, in 1920s, his research focused on the mutagenic effects of different forms of radiation on economically important plants like maize and barley. Lewis J. Stadler, 1896- 1954 42  Ultracentrifuge 1925 – Theodor Swedberg developed his ultracentrifuges: the key to colloid solutions: the distribution of particle size. In the ultracentrifuge, large molecules such as proteins and carbohydrates were spun fast enough to subject them to thousands of times the force of gravity, ultimately up to about 106 g. 1884-1974, Theodor Swedberg, Biochemist. Nobel prize for Chemistry in 1926  Genetic Trait is Transfered by DNA In 1928 - Frederick Griffith reported what is now known as Griffith's Experiment, the first widely accepted demonstrations of bacterial transformation, whereby a bacterium distinctly changes its form and function.. ‘’ an unidentified transforming principle or transforming factor’’ Frederick Griffith (1879– Image modified from "Griffith experiment," by Madeleine Price Ball (CC0/public domain)._ 1941) , bacteriologist  Genetic Trait is Transfered by DNA In 1944 - Oswald Avery (1877 –1955) and his colleagues McLeod , McCarty proved that ‘’Genetic Trait is Transfered by DNA.’’ Identifying the ‘’transforming principles’’ by Setting out Griffit’s experiment....... “Genes are made of DNA”.... q The chromosome is composed of a polymer of some kind as a string of genes: A long string of DNA: "beads on a string," q DNA is the one transfers a genetic trait. physician and medical researcher, one of the first molecular biologists and pioneer in immunochemistry  The Molecular Nature of Genes: Rosalind ‘’James Watson selling Nobel prize Franklin 'because no-one wants to admit I exist‘, (1920- 1958) 2014’’ 1953-The double helix structure of DNA James Watson was first discovered by James Watson (1928-) , Francis and Francis Crick, using experimental data Crick (1916-2004). Nobel prize in Maurice Wilkins collected by Rosalind Franklin and Maurice medicine, 1962 (1916-2004), Wilkins. Nobel prize in medicine, 1962 DNA double helix Two complementary strands of DNA sequences The Molecular Nature of Genes Computer model of the DNA double helix.© Comstock Images/Jupiter RF.  Gene to protein: tRNA In 1957 – Mahlon Hoagland and Paul C. Zamecnik showed that amino acids had to be energized, "activated," by ATP before they were incorporated into a peptide chain. This led to the identification of ‘tRNA, an adaptor molecule’’. The results were served to connect two fields of science research, biochemistry and molecular biology....... “”.... a, Mahlon Hoagland, Paul Zamecnik, and Mary Stephenson. b, Paul C. Zamecnik (1912- 2009) same characters, Mahlon Hoagland (1921-2009 ) approximately 35 physician and biochemist, physician and biochemist, years later. JBC,2005 medical researcher medical researcher 1941-The Relationship Between Genes and Proteins: A gene is responsible for the production of an enzyme: “One Gene/One enzyme” Sir Archibald Edward Garrod ( 1857 – 1936) 1902- Garrod prefigured “one gene- one enzyme”, also discovered alkaptonuria, understanding its inheritance. Garrod observed that..’’alcaptonuria behaved genetically as a Mendelian recessive trait’’.. and suggested that ‘a defective gene gives rise to a defective enzyme’ 1958- George Beadle and E. L. Tatum proved that:...’’A gene is responsible for the production of an enzyme’’... G. Beadle Nobel Prize in Physiology or Medicine Nobel laureate who with E. Tatum Edward Lawrie Tatum (1909 – George Wells Beadle (1903 –1989) 1975)  LIFE BEGINS WITH CELLS 1. The Diversity and Commonality of Cells 2. The Molecules of a Cell 3. The Work of Cells 4. Investigating Cells and Their Parts 5. A Genome Perspective on Evolution the human egg cell with sperm cells  1.1.INTRODUCTION: UNITY AND DIVERSITY inner ear and parathyroid gland  1. Diversity and Commonality Of Cells q Cells come in amazing variety shapes and sizes. q Some move rapidly, others move fast, change their structure fast, e.g amoeba. Others are largely stationary and structurally stable. q Oxygen kills some, but is an absolute requirement for others. q Most cells in multicellular organisms are involved with other cells. q Some unicellular organisms live in isolation, others form colonies or live in close association with other types of organisms. E.g. The bacteria that helps plants to extract nitrogen from the air or the bacteria live in human gut to help to digest food. q Despite other differencies, all cells share certain structural features and carry out many complicated processes in basically the same way. Cells come in amazing variety shapes and sizes and with different energy types and function for others. a) Eubacteria; note dividing b) Archaebacteria produce c) The red blood cells are their energy by converting oxygen-bearing cells. carbon dioxide and erythrocytes, the white These are hydrogen gas to methane. blood cells (leukocytes) are Lactococcus part of the immune system lactis, Some species that live in and fight infection, and the which are used the rumen of cattle give green cells are platelets that to produce rise to >150 liters of provide substances to make cheese. methane gas/day. blood clot at a wound.  Cells come in amazing variety shapes and sizes and with different energy types and function for others. f) A single Purkinje g) Cells can form an h) Plant cells are fixed neuron of the epithelial sheet, firmly in place in vascular cerebellum, which can through intestine. New plants, supported by a form more than a cells form continuously rigid cellulose skeleton. hundred thousand near the bases of the Spaces between connections with other villi, and old cells are the cells are joined into cells through the shed from the top. tubes for transport of branched network of dendrites. water and food  Linneaus Biological Classification Today the system of classification When Carl Linnaeus developed his includes six kingdoms. biological classification (1735), there were only two kingdoms, Plants and The Six Kingdoms: Animals... Plants, Animals, Protists, Fungi, Carl von Linneaus When identifying an object, Linnaeus Archaebacteria, Eubacteria. (1707- 1778 ), first looked at whether it was animal, Swedish botanist, vegetable, or mineral. How are organism placed into their zoologist, and These three categories were the kingdoms? physician original domains. Domains were divided into kingdoms, · Cell type, complex or simple which were broken into phyla · Their ability to make food (singular: phylum) for animals and · The number of cells in their body divisions for plants and fungi. Phyla or divisions were broken into classes, which in turn were divided into orders, families, genera (singular: genus), and species. Species were divided into subspecies. In botany, species were divided into varietas (singular: variety) and forma (singular: form).  The hierarchy of biological Life timeline classification's (major taxonomic ranks). About the Domains/Kingdoms: This diagram implies 3 Domains / 6 Kingdoms (Woese et al. 1990: Archaea, Domain (and Kingdom) Eukarya, Domain Protista, Kingdom Fungi, Kingdom Animalia, Kingdom Plantae, Kingdom Bacteria, Domain (and Kingdom) Adapted from Woese et al. 1990  Classification of Living Things: Domains of Life q All organisms from simple bacteria to complex mammals probably evolved from a common, single-celled progenitor. q All cells are thought to have evolved from a common progenitor because the structures and molecules in all cells have so many similarities. q All living things are grouped into three domains: q Bacteria (domain and kingdom) q Eukaryota: Kingdoms: Protists (single-celled), Fungi, Plants, Animals q Archaea (domain and kingdom) q Although the archaea resemble the bacteria physically, some aspects of their molecular biology are more similar to those of eukaryota. In summary, The Three Domains of Life  Three Domains Morphological criteria: This family tree depicts the evolutionary relations among the three of Life major lineages of organisms. The structure of the tree was initially ascertained from morphological criteria: Creatures that look alike were put close together. (a) DOMAIN BACTERIA (b) DOMAIN ARCHAEA (c) DOMAIN EUKARYA Protists Kingdom Plantae Kingdom Fungi Kingdom Animalia  All Cells Are Prokaryotic or Eukaryotic The biological universe consists of TWO GENERAL TYPES OF CELLS: A. Prokaryotic ("before nucleus") cells: Found in prokaryotes (bacteria). B. Eukaryotic ("true nucleus"): Found in eukaryotes.  CHARACTERISTICS OF PROKARYOTIC & EUKARYOTIC CELLS Basic features of all cells: 1. Cell or plasma membrane 2. Genetic material: Chromosomes carry genes (DNA) 3. Semifluid subtances called cytosol (cytoplasm) 4. Ribosomes (make proteins) Prokaryotic/Eukaryotic Cells a) Electron micrograph of a thin section of Escherichia coli, a common intestinal bacterium. a) Electron micrograph of a plasma cell, a type of white blood cell that secretes antibodies CHARACTERISTICS OF PROKARYOTIC (BACTERIAL) CELLS Prokaryotic cells are characterized by having – No nucleus – DNA in an unbound region called the nucleoid – No membrane-bound organelles – Cytoplasm bound by the plasma membrane  A. Prokaryotic (“Before Nucleus") cells-Summary q Prokaryotic cells are consist of a single closed compartment that is surrounded by the plasma membrane. Plasma membrane is composed of phospholipid bilayer, containing membrane lipids and proteins. q Prokaryotic cell lack a membrane-bound nucleus and membrane-bound organelles. These cells do have some organelles which are not membrane-bound (e.g. ribosomes). q All prokaryotes have this type of the cells. q Prokaryot (Bacteria) chromosomes are arranged in a single closed DNA circle (nucleoid). The nucleoid, consisting of the bacterial DNA, is not enclosed within a membrane (chromosomal DNA). In addition to the chromosome, Bacteria also contain smaller circular DNA molecules called plasmids. q All prokaryotic cells have a cell wall, its main component is peptidoglycan (except Mycoplasms). q Prokaryotic cells are much smaller than eukaryotic cells (about 10 times smaller); their small size allows them to grow faster and multiply more rapidly than eukaryotic. qThey come in many shapes and sizes. Bacteria, the most numerous prokaryotes, are single-celled (unicellular) organisms; Cyanobacteria (or often are called ‘’blue-green algae’’) can be single-celled or filamentous chains of cells.  Bacterial Cells Bacterial cells are significantly smaller than eukaryotic cells and are typically at 0.1–5.0 µm in diameter. A single Escherichia coli bacterium has a dry weight of ≈25x 10-14 g. Human body contains bacteria that weighs ≈ 1–1.5 kg. The estimated number of bacteria on earth is 5x1030, weighing a total of about 1012kg. Prokaryotic cells have been found 7 miles deep in the ocean and 40 miles up in the atmosphere; they are quite adaptable! The carbon stored in bacteria is nearly as much as the carbon stored in plants. (one million million; 1012) = trillion PROKARYOTIC CELL STRUCTURE A. Appendages 1. Pili 2. Flagella (singular – flagellum) 3. Axial Filaments B. Cell Envelope (layers from outside to inside) 1. Glycocalyx - sugar coat, often called a capsule 2. Outer Membrane: composed of a bilayer membrane; the inner layer is composed of phospholipids; the outer layer is composed of lipopolysaccharides, (part of it is hydrophobic, part is hydrophilic) a compound that's not found in any other living organism! 3. The Cell Wall: All prokaryotic cells have a cell wall, its main component is peptidoglycan. A cell wall affect the shape of a cell. Function: 1. Cell Shape 2. Withstanding Turgor pressure 4. Periplasm: A space between the cell membrane and the peptidoglycan cell wall;contains proteins to break down certain nutrients into smaller molecules. 5. Plasma or Cell Membrane: Encloses the cytoplasm of any cell. Major function is to contain the cytoplasm and to transport and regulate the molecules comes in and out of the cell; composed of membrane lipids and proteins, Many prokaryotic cell membranes are similar to those in eukayotics 6. Cytoplasm  PROKARYOTIC CELL STRUCTURE Three basic forms: A typical structure of prokaryotic cells Rod shaped (bacillus) Sperical shaped (coccus) Spiral shaped (spirillum or spirochetes) Prokaryotic Cells: Escherichia Coli, A Common Intestinal Bacterium The nucleoid, consisting of the bacterial DNA, is not enclosed within a membrane. E. Coli and some other bacteria are surrounded by two membranes separated by the periplasmic space. The thin cell wall is adjacent to the inner membrane.  A. Cyanobacteria ‘’blue-green algae’’ Scanning electromicrograph of Marine cyanobacteria (Spirulina platensis), Gram-negative, Spirulina sp enriched foods. İsotonic oxigenic, photosynthetic, Aztecs collecting tecuitlatl drinks (a), chruncy bars (b) premade filamenteous cyanobakteria soups (c), pudding (d) mixed cake flours (prokaryota). (spirulina, blue-green algae. Human Nature, March 1978. (e) and biscuits (f). Da Silva Va zetal. DENNISKUNKELMICROSCOPY (by Peter T. Furst) den Curr. Opin.,2016 /SCIENCE PHOTO LIBRARY alıntı.. Locals use dihé sauce poured over millet. Photo: Marzio Marzot, FAO Report The Future is an Ancient Lake, 2004.  Eukaryotes Eukarya Domain includes several kingdoms : - Protista, Kingdom:free-living and parasitic microscopic protists (Protozoa, "animal-like’’; which are exclusively unicellular such as flagellata; protophyta the "plant-like"(mostly unicellular algae); Molds the "fungus- like" (e.g..slime molds and water molds) - Fungi, Kingdom: exist in both: q multicellular forms (molds) and q unicellular (single-celled) forms (yeasts) – Animalia, Kingdom – Plantae, Kingdom  CHARACTERISTICS OF EUKARYOTIC CELLS Eukaryotic cells are characterized by having – DNA in a nucleus that is bounded by a membranous nuclear envelope – Membrane-bound organelles – Cytoplasm in the region between the plasma membrane and nucleus Eukaryotic cells are generally much larger than prokaryotic cells. B. Eukaryotic ("true nucleus") – Summary q Eukaryotic cells, unlike prokaryotic cells contain a membrane-bound nucleus and membrane-bound organelles; evolved about 2 million years after the prokaryotes. q Plasma Membrane encloses the cytoplasm of any cell. Made of phospholipid bilayer. Contains membrane lipids (primarily phosholipid bilayer) and membrane proteins (integral, peripheral, lipid-anchored). q Eukaryotic chromosomes (genetic material: DNAand proteins) are linear, are isolated in the nucleus that is surrounded by a nuclear envelope (double membrane of fosfolipid bilayer with nuclear pores). Nucleus is the "control center of the cell.“ isolates the DNA in eukaryotic cells, carrier of the hereditary information. q Cytoplasm is the region of the cell lying between the plasma membrane and the nucleus is the cytoplasm. Comprises the cytosol (aqueous phase) and organelles. Cytoskeleton (network of filamentous protein structures) (not found in prokaryotes) exist. q Cell walls are sometimes present, but they are composed of cellulose or chitin. Animal cells - no cell wall! q Eukaryotic organisms with eukaryotic cells include Protista (free-living and parasitic microscopic mostly unicellular organisms), Fungi, (exist in both multicellular forms (molds) and unicellular forms (yeasts), Animalia and Plantae Kingdoms.  Eukaryotic Cells Eukaryotic cells are commonly about 10–100 µm across, generally much larger than bacteria. A typical human fibroblast, a connective tissue cell, might be about 15 µm across with a volume and dry weight some thousands of times those of an E. Coli bacterial cell. An amoeba, a single-celled protozoan, can be more than 0.5 mm long. An ostrich egg begins as a single cell that is even larger and easily visible to the naked eye.  EUKARYOTIC CELL STRUCTURE A. Appendages 1. Cilia - short, hairlike, motile cellular extensions that occur on the surfaces of certain cells; ex. some protozoa (called Ciliates) use cilia for motility and feeding. 2. Flagella - in humans, the single, long, hairlike cellular extension that occurs in sperm cells; beat in waves (prokaryotic flagella rotate!); some protozoans use flagella for motility. B. Cell walls are sometimes present, but they are composed of cellulose or chitin. Animal cells - no cell wall! C. Glycocalyx may exist outside the plasma membrane; composed of carbohydrate chains from glycoproteins in cell membrane. D. Plasma Membrane Encloses the cytoplasm of any cell. Major function is to contain the cytoplasm and to transport and regulate the molecules comes in and out of the cell. Contains Membrane lipids (primarily phosholipid bilayer) and Membrane proteins. Many prokaryotic cell membranes are similar. Differences: Proteins involved in electron transport chain are found in the organelles membranes; Eukaryotic cell membrane contains cholesterol (in prokaryotes, only mycoplasmas have it). E. Cytoplasma F. Nucleus G. Ribosomes: not membrane-bound ; site of protein synthesis H. Membrane-bound organelles Eukaryotic cells have specializes membrane-bound organelles that carry out specific functions such as photosynthesis (chloroplasts), E.g. ATP production (mitochondria),  EUKARYOTIC CELL STRUCTURE An illustration of a generalized, single-celled eukaryotic organism. A Plasma cell, a type of white blood cell that secretes antibodies. Only a single membrane (the plasma membrane) surrounds the cell, but the interior contains many membrane- limited compartments, or organelles.  ARCHAEA (ARCHAEBACTERIA OR ARCHAEANS) All cells are thought to have evolved from a common progenitor because the structures and molecules in all cells have so many similarities. In recent years, detailed analysis of the DNA sequences from a variety of prokaryotic organisms has revealed two distinct types: 1. true bacteria, or eubacteria, and 2. archaea (also called archaebacteria or archaeans) Eubacteria (True bacteria) and Archaea (Archaebacteria or Archaans) are Different. Archae are morphologically similar to bacteria in size and shape, but their molecular biology is closely related to those of eukaryotes. The hot springs of Yellowstone National Park, USA, were among the first places Archaeans and other microbes were discovered. Thermophiles, a type of extremophile, produce some of the bright colors of Grand Prismatic Spring, Yellowstone National Park.  Nature: metan Archaea (CH4), an odorless and (Archaebacteria) inert gas Many archaeans grow in unusual, often extreme, environmental conditions like high pressure and temperature that may resemble ancient conditions when life first appeared on earth. Archaea: major metabolic groups : Halophiles, sulfur metabolizers and methanogens Halophiles ( salt loving ) require high concentrations of salt to survive Most extreme halophiles are chemoheterotrophic. Thermoacidophiles ( heat and acid loving ) grow in hot (80 C) sulfur springs, where a pH of less than 2 is common. Methanogens (‘’methane (CH4) producers’’ ) live in oxygen-free milieus and generate methane (CH4) by combining water with carbon dioxide as part of energy metabolism. Strictly anaerobic, autotrophs. Cows can produce up to 600 liters of methane every day! This accounts for about 15% of global methane production. Disastrous for global warming? Unicellular (Single-celled) Organisms Help and Hurt Us Bacteria , e.g E. Coli helps us to digest our food, q The other group of single-celled but streptomyces gives us strep throat. eukaryotes, the yeasts, also have their Like bacteria, protozoa (unicellular Eukaryotes) good and bad points, as do their have key roles in the fertility of soil. many multicellular cousins, the molds.Yeasts Plasmodium species) do give us grief. The four and molds, which collectively constitute Plasmodium species that cause malaria in the fungi, have an important ecological humans. Each year the worst of the protozoa, role in breaking down plant and animal Plasmodium falciparum and related species, is remains for reuse, also make numerous the cause of more than 300 million new cases of antibiotics and they are used in the malaria, a disease that kills 1.5 to 3 million manufacture of bread, beer, wine, and people annually. cheese. Not so pleasant are fungal diseases such as athlete s foot. Athlete's foot (tinea pedis) Single-celled organisms can be reproduced both: - sexually (mating) (Figure A) by meiosis as haploid cells when nutrients are limiting -asexually (through a process known as budding) (Figure B) by mitosis as diploid cells Figure A Figure B q The Yeast Saccharomyces Cerevisiae, like all fungi, Reproduces Sexually (Mating) by meiosis as haploid cells when nutrients are limiting. q The common yeast used to make bread and beer, Saccharomyces cerevisiae, has proven to be a great experimental organism. q Like many other unicellular organisms, yeasts have two mating types like the male and female gametes (eggs and sperm) of higher organisms. q Two yeast cells of opposite mating type can fuse, or mate, to produce a third cell type containing the genetic material from each cell. q Such sexual life cycles allow more rapid changes in genetic inheritance than would be possible without sex, resulting in valuable adaptations while quickly eliminating detrimental mutations. That, and not just Hollywood, is probably why sex is so ubiquitous. The Yeast Saccharomyces Cerevisiae Reproduces Asexually (Budding) Scanning electron micrograph of budding yeast cells. After each bud breaks free, a scar is left at the budding site so the number of previous buds can be counted. The orange cells are bacteria. Pathogens in many forms: Viruses are not classified as living things (A) The structure of the protein coat, or capsid, of poliovirus. This virus was once a common cause of paralysis, but the disease (poliomyelitis) has been nearly eradicated by widespread vaccination. (B) The bacterium Vibrio cholerae, the causative agent of the epidemic, diarrheal disease cholera. (C) The protozoan parasite Toxoplasma gondii. This organism is normally a parasite of cats, but it can cause serious infections in the muscles and brains of immunocompromised people with AIDS. (D) This clump of Ascaris nematodes was removed from the obstructed intestine of a two-year-old boy. (adapted from Amer. J. Trop. Med. Hyg. 35:314–318, 1986)  What are Viruses? Viruses Are the Ultimate Parasites. Viruses Must Infect A Host Cell To Grow And Reproduce q Virus-caused diseases are numerous and all too familiar: chicken pox, influenza, and many others. q Smallpox, once a worldwide scourge, in the mid-1960s, Viral infections in plants (e.g. dwarf mosaic virus in corn) q Most viruses have a rather limited host range, infecting certain bacteria, plants, or animals. q Viruses cannot grow or reproduce on their own, not considered to be alive. q Viruses must infect a host cell and take over its internal machinery to synthesize viral proteins and in some cases to replicate the viral genetic material to survive. q The cycle starts a new.  Viruses q Much smaller than cells, on the order of 100 nanometer(nm) in diameter; in comparison, bacterial cells are usually 1000 nm (1 nm=10-9 meters). q Typically composed of a protein coat that encloses a core containing the genetic material, which carries the information for producing more viruses. q Protected by the coat from the environment and be allowed to stick to, or enter, specific host cells. In some viruses, the protein coat is surrounded by an outer membrane-like envelope. q The ability of viruses to transport genetic material into cells and tissues represents a medical menace and a medical opportunity. q Viral infections can be devastatingly destructive. q However, many methods for manipulating cells depend upon using viruses to convey genetic material into cells.  What are Viruses? Viruses Are the Ultimate Parasites. Viruses Must Infect A Host Cell To Grow And Reproduce Tobacco mosaic virus causes a mottling of the leaves of infected tobacco plants and stunts their growth. T4 bacteriophage (bracket) attaches to a bacterial cell via a tail structure. Viruses that infect bacteria are Adenovirus causes eye called bacteriophages, or and respiratory tract simply phages. infections in humans  LIFE BEGINS WITH CELLS: We Develop from a Single Cell: A Zygote A single ~200 micrometer (µm) cell, the human egg, with sperm, which are also single cells. In 1827, German physician Karl von Baer discovered that mammals grow from eggs that come from the mother s ovary. q Every human being begins as a zygote (the union of an egg and sperm), which houses all the necessary instructions for building the human body containing about 60-100 trillion (1014) cells, an amazing feat. q Human body is made up of about 200 different types of cells. qCells with the capability to give rise to an entire body of the organism are referred to as embryonic stem (ES) cells.  A living organism can not be developed into a complex structure without a cell. without being a cell. Our organs and tissues are the living part of the body which are made up of cells that collectively work together with specialized functions. We Develop from a Single Cell: A Zygote qAn organism begins life as a single cell to make a copy of itself (yumurta ve sperm). Thus, living organism can not be developed into a complex structure without a cell. without being a cell. q The’’ information’’ inside of the cell define the internal mechanisms which defines in what kind of creature it actually would be developed. (e.g. A frog or a human) bir kurbağa mı veya bir insanmı)  COMPARATIVE SIZES: PARTS AND WHOLES It is useful to think of life’s organization in levels, from the simple to the complex: from atoms to simple molecules, to chain molecules , to molecular structures, to cells, to organs, to organisms, to populations, to community and to ecosystems A higher level includes everything in the levels below it. This way of getting to understand the whole by learning about its parts, called reductionism, has produced in the last several decades an explosion of knowledge about what genes are and how they work, and how living processes are energized, informed, operated, and controlled. Organisms such as bacterium, yeast. Human organism -60 trilion cells > Organs -Group of Cells > Cells -The smallest living units > Structures –The largest structure is 10X> The smallest structure is 100X> Chain Molecules 500X> Molecules -10X> Atoms –average weight is 15 atom units The relative scale of biological molecules and structures Cells can vary between 1 micrometer (μm) and hundreds of micrometers in diameter. Within a cell, a DNA double helix is approximately 10 nanometers (nm) wide, whereas the cellular organelle called a nucleus that encloses this DNA can be approximately 1000 times bigger (about 10 μm). See how cells compare along a relative scale axis with other molecules, tissues, and biological structures (blue arrow at bottom). Note that a micrometer (μm) is also known as a micron. © 2010 Nature Education All rights reserved.  We Develop from a Single Cell q Development begins with the fertilized egg cell dividing into two, four, then eight cells, forming the very early embryo. qConfirmed cell proliferation and differentiation into distinct cell types gives rise to every tissue in the body. q One initial cell, the fertilized egg (zygote), generates hundreds of different kinds of cells that differ in content, shape, size, color, mobility, and surface composition. qMaking different kinds of cells – muscle, skin, bone, neuron, blood cells – is not enough to produce the human body. qThe cells must be properly arranged and organized into tissues, organs, and appandages. q Our two hands have the same kinds of cells, yet their different arrangements—in a mirror image—are critical for function. q Polarity: In addition, many cells exhibit distinct functional and/or structural asymmetries, a property often called polarity. q From such polarized cells arise asymmetric, polarized tissues such as the lining of the intestines and structures like hands and hearts. Identical twins occur naturally when the mass of cells composing an early embryo divides into two parts, each of which develops and grows into an individual animal.  Embryonic and adult stem cells Stem cell plasticity. The most primitive, undifferentiated cells in an embryo are embryonic stem cells. Their ability to differentiate into a number of cell types is called plasticity. (adapted from lippincott cell mol biol) EMBRYONIC STEM (ES) CELLS qEach cell in an eight-cell-stage mouse embryo has the potential to give rise to any part of the entire animal. The first few cell divisions of a fertilized egg set the stage for all subsequent development: A developing mouse embryo is shown at (a) the two-cell, (b) four-cell, and (c) eight-cell stages. The embryo is surrounded by supporting membranes. The corresponding steps in human development occur during the first few days after fertilization. ‘’Stem Cells, Cloning, and Related Techniques Offer Exciting Possibilities but Raise Some Concerns’’ qThe scientific interest comes from learning the signals that can unleash the potential of the genes to form a certain cell type. q The medical interest comes from the possibility of treating the numerous diseases in which particular cell types are damaged or missing, and of repairing wounds more completely. Five genetically identical cloned sheep  New properties emerge at each level in the biological hierarchy The biosphere Cells Organs and 10 µm organ systems Cell Ecosystems Organelles Communities 1 µm Atoms Tissues 50 µm Populations Molecules Organisms Life can be studied at different levels from molecules to the entire living planet. The study of life can be divided into different levels of biological organization  Organisms interact with their environments, exchanging matter and energy Every organism interacts with its environment, including nonliving factors and other organisms Both organisms and their environments are affected by the interactions between them For example, a tree takes up water and minerals from the soil and carbon dioxide from the air; the tree releases oxygen to the air and roots help form soil Ecosystem Dynamics The dynamics of an ecosystem include two major processes: – Cycling of nutrients, in which materials acquired by plants eventually return to the soil – The flow of energy from sunlight to producers to consumers  Energy Conversion Work requires a source of energy Energy can be stored in different forms, for example, light, chemical, kinetic, or thermal The energy exchange between an organism and its environment often involves energy transformations Energy flows through an ecosystem, usually entering as light and exiting as heat  A calori (cal) is eqivalent to JAMES PRESCOTT James Prescott Joule, experimentally JOULE the amount of heat needed (1818-1889) proved the first law of thermodynamics, to raise the temperature of 1 determined the mechanical equivalent of gram of water from 14.5 to heat (The unit Joule ) in 1843. A Joule (J) is 15.5 °C. A kilocalorie (kcal) the amount of energy required to apply a 1 is equal to 1,000 cal. Also newton force over a distance of 1 metre. 1kcal = 4.184 kJ. CONCEPT OF 1 kilojoule (kJ) = 1,000 J. ENERGY Some of the common examples of transformations of energy in biological systems (a) (b) (c) Transformation of energy in biological systems (a) The running horse represents conversion of chemical energy to mechanical energy. (b) The electric fish (Torpedinidae) converts chemical energy to electrical energy. (c) The phosphorescent bacteria convert chemical energy into light energy.  Sunlight Ecosystem Nutrient Producers cycling and (plants and other photosynthetic energy Cycling organisms) Heat flow in an of chemical ecosystem nutrients Chemical energy Consumers (such as animals) Heat  Flow of Energy To make a living cell requires matter, as well as free energy. To survive, ecosystems need a constant of energy from sunlight or chemicals. Energy enters ecosystems in the form of sunlight or chemical compounds. Producers, also called autotrophs or inorganotrophs: organisms that use this energy (from sunlight or chemical compounds) to make food. Two types of autotrophs: photoautotrophs and chemoautotrophs. Plants, alg, some bacteria (cyanobacteria), archae. Consumers, also called heterotrophs or organotrophs: organisms that get energy by eating the food. Herbivores (rabbit), carnivores (lion), omnivores (humans, Gut bacteria-E.Coli). Decomposers: organisms that get energy by decomposing the dead organisms. vultures, millipedes, dung beetles, fungi (the only organisms that can decompose wood).  Primary sources of energy: An organism can be an organotroph or inorganotroph. Living organisms obtain their free energy in different ways: 1. By feeding on other living things or the organic chemicals they produce (Organotrophic, Consumers, also called heterotrophs or organotrophs) q Organotrophic organisms (Gk trophe, meaning food ). Animals, fungi, and the bacteria that live in the human gut, 2. By feeding directly from the nonliving world (meaning ‘’Inorganic’’) (Inorganotrophic, Producers, also called autotrophs or inorganotrophs). Autotrophs fall into two classes: qPhototrophic organisms (feeding on sunlight): havest the energy of Sunlight. Plants, alg, some bacteria (cyanobacteria). q Chemoautotrophic (Lithotrophic) organisms (feeding on chemicals-rock): from energy-rich systems of inorganic chemicals in the environment. Microscopic and mostly live in habitats that humans do not frequent—deep in the ocean, buried in the Earth's crust, or in various other inhospitable environments. Archae. These are primary energy converters. 3. By decomposing the dead organisms: vultures, millipedes, dung beetles, fungi (the only organisms that can decompose wood). q Organotrophic organisms could not exist without these primary energy converters, which constitute the largest mass of living matter on Earth.  To survive, ecosystems need a constant of energy from sunlight or chemicals. Energy enters ecosystems in the form of sunlight or chemical compounds. A food chain shows how energy and matter flow from producers to consumers. ck12.org/biology Tubeworms deep in the Galapagos Rift This diagram compares and get their energy from chemosynthetic contrasts photosynthesis and bacteria living within their tissues. No cellular respiration. It also shows digestive systems needed! Dung Beetle.. ck12.org/biology how the two processes are ck12.org/biology related. ck12.org/biology Primary sources of energy: An organism can be an organotroph or inorganotroph. Energy Converters: Inorganotrophic bacteria The geology of a hot hydrothermal vent in the ocean floor. A temperature gradient is set up, from more than 350 C near the core of the vent, down to 2–3 C in the surrounding ocean. Minerals precipitate from the water as it cools, forming a chimney. Different classes of organisms, thriving at different temperatures, live in different neighborhoods of the chimney. A typical chimney might be a few meters tall, with a flow rate of 1–2 m/sec.  We obtain free enerji from metabolic fuels (Foods): Sugars, Proteins, Lipids, Vitamins, Mineraller Mitochondria ‘’power plants’’ Molecular Motor- ATP SYNTHASE  q Energy is required: One of the ATP IS THE best-known small molecules is UNIVERSAL ATP. ENERGY q In many cases, the source of energy for chemical reactions CURRRENCY IN in cells is the hydrolysis of the BIOLOGICAL molecule ATP. SYSTEMS. q ATP stores readily available chemical energy in two of its The ATP cycle in cells chemical bonds. The overall reaction may be written as: C6H12O6 + 6O2 ® 6CO2 + 6H2O, but the process is much more complicated than the given formula. 2. Small Molecules of the Cell and Their Functions A. Water Can Interacts With Water And Other Biomolecules. B. Small Molecules Carry Energy, Transmit Signals, and Are Linked into Macromolecules. C. Proteins Give Cells Structure and Perform Most Cellular Tasks. D. Nucleic Acids Carry Coded Information for Making Proteins at the Right Time and Place. E. The Genome Is Packaged into Chromosomes and Replicated During Cell Division. F. Mutations May Be Good, Bad, or Indifferent. LIFE OCCURS IN WATER: THE MOLECULE THAT SUPPORTS ALL OF LIFE: WATER Water is the biological medium on Earth All living organisms require water more than any other substance.Most cells are surrounded by water, and cells themselves are about 70–95% water.The abundance of water is the main reason the Earth is habitable Size and speed are related. The smaller is object, the faster is. Water is a fast, small molecule. Water molecules swim about at stupendious speeds, flashing past each other and bumping into each other every millionth of a millionth of a second. Life depends upon these frequent and vigorous collisions. The water molecule is a polar molecule: The opposite ends have opposite charges Polarity allows water molecules to form hydrogen bonds with each other Four of water’s properties that facilitate an environment for life are: Cohesive behavior: Surface tension is related to cohesion, Ability to moderate temperature, Expansion upon freezing, Versatility as a solvent Surface tension is related to cohesion A. Water (H2O) is the most abundant molecule in cells (70% or more of total cell mass). Cells are composed of water, inorganic ions, and carbon-containing Organic molecules. Water Can Interacts With Water And Other Biomolecules. Water (H2O) B. Small Molecules carry Energy, transmit Signals, and are Linked into Macromolecules q Much of the cell’s contents is a watery soup flavored with small molecules (e.g. simple sugars, amino acids, vitamins) and ions (e.g., sodium, chloride, calcium ions). Water can interacts with water and other biomolecules. qThe locations and concentrations of small molecules and ions within the cell are controlled by numerous proteins inserted in cellular membranes (e.g. pumps, transporters, and ion channels). These pumps, transporters, and ion channels move nearly all small molecules and ions into or out of the cell and its organelles. q Adenosine triphosphate (ATP) is One of the best-known of small molecules, is an energy carrier.  B. Small Molecules carry Energy, transmit Signals, and are Linked into Macromolecules q Signal molecules: Other small molecules act as signals both within and between cells; e.g. Hormones (e.g. Epinephrin-a small hormone that mobilizes the “fight or flight” response), and neurotransmitters (fight or flee are triggered by nerve impulses from the brain to our muscles aids of another type of small-molecule signal neurotransmitters) qCovalent And Noncovalent Linkage Of Monomers To Form Biopolymers And Membranes: q Covalent and noncovalent interactions stabilize the molecules. q Monomers/Polymers: Certain small molecules (monomers) can be joined to form polymers through repetition of a single type of chemical-linkage reaction. Cells produce three types of large polymers, commonly called macromolecules: polysaccharides, proteins, and nucleic acids. Sugars, for example, are the monomers used to form polysaccharides, critical structural components of plant cell walls and insect skeletons. Fatty acids form more complex lipid polymers called triglycerides, triacylglycerols or triacylglycerides. qTwo polymers- proteins and nucleic acids exhibit the greater informational complexity. Functional Groups of Molecules: Carbohydrates are composed of monosaccharides: common sugar is glucose ( grape sugar) Functional Groups of the molecules: Lipids are composed of long fatty acids chains. E.g. A Membrane lipid, phosphatidylcholine is composed of a hydrophilic head ( a phosphate group and alcohol) attached to a glycerol backbone linked to two fatty acids  Functional groups of molecules: Proteins are composed of amino acids: Cells string together 20 different amino acids in a linear chain to form a protein. Functional groups of molecules: Nucleic acids DNA and RNA are generated by a sugar, a base and a phosphate group by covalent, noncovalent bonds. DNA: Thymine, a deoxyribose; RNA: uracil and a ribose Monomers/Polymers: Certain small molecules (monomers) can be joined to form polymers through repetition of a single type of chemical-linkage reaction. Cells produce three types of large polymers, commonly called macromolecules: polysaccharides, proteins, and nucleic acids. Sugars, for example, are the monomers used to form polysaccharides, critical structural components of plant cell walls and insect skeletons. Fatty acids form more complex lipid polymers called triglycerides, triacylglycerols or triacylglycerides. qTwo polymers- proteins and nucleic acids exhibit the greater informational Covalent And Noncovalent Linkage Of complexity. Monomers To Form Biopolymers And Membranes. Covalent and noncovalent interactions stabilize the molecules. Structure And Function Of Major Biological Molecules Of The Cell Cellulose-digesting prokaryotes Our Debt to Fat: Cell Membrane are found in grazing animals such as this cow General aspects of protein structure: Schematic diagram of the primary, secondary, tertiary, and quaternary The genetic material structures of a protein.  C. Proteins Give Cells Structure and Perform Most Cellular Tasks Proteins vary greatly in size, shape, and function: The varied, intricate structures of proteins enable them to carry out numerous functions. E.g., a small size hormone transmits external signals through surface receptor or can act within a cell through gene expression; An ion channel is inserted in cell membrane can control location and concentration of ions within the cell; enzymes catalyse chemical reactions. Proteins commonly range in length from 100 to 1000 amino acids, but some are much shorter and others longer. If a “typical” protein is about 400 amino acids long, there are 20400 possible different protein sequences.  D. Nucleic Acids Carry Coded Information for Making Proteins at the Right Time and Place. DNA Replication From DNA to Proteins  E. The Genome Is Packaged into Chromosomes and Replicated During Cell Division q The genome is packaged into chromosomes: Most of the DNA in eukaryotic cells is located in the nucleus, extensively folded into the familiar structures we know as Chromosomes. q Each chromosome contains a single linear DNA molecule associated with certain proteins. q The genome of an organism comprises its entire complement of DNA. Nucleus DNA Nucleotide Cell (a) DNA double helix (b) Single strand of DNA  E. The Genome Is Packaged into Chromosomes and Replicated During Cell Division The genome is replicated during cell division. q Every time a cell divides, the two strands of double helical DNA in the chromosomes is separated. The outcome is a pair of double helices, each identical to the original and the copying has to be rapid, highly accurate. q With the exception of eggs and sperm, every normal human cell has 46 chromosomes. Half of these, and thus half of the genes, can be traced back to Mom; the other half, to Dad. (Left) A chromosome spread from a human body cell midway through mitosis, when the chromosomes are fully condensed. (Right) Chromosomes from the preparation on the left arranged in pairs in descending order of size, an array called a karyotype.  F. Mutations May Be Good, Bad, or Indifferent qMistakes occasionally do occur spontaneously during DNA replication, causing changes in the sequence of nucleotides. qSuch changes, or mutations, also can arise from radiation that causes damage to the nucleotide chain or from chemical poisons, such as those in cigarette smoke, that lead to errors during the DNA-copying process. qMutations come in various forms: a simple swap of one nucleotide for another; the deletion, insertion, or inversion; and translocation of a stretch of DNA from one chromosome to another. SİZE AND SURFACE Wrinkles and bumps allowed the elephant’s ancestors to get bigger. Increasing surface area by creating hills and valleys also allowed organs such as intestines, lungs and brains to increase their functional capacity while confined within a limited body space. Insertion: Hungtinton disease A mistake for one organism can be an advantage for another. Albinism, a defect in pigmentation, occasionally shows up in many kinds of plants and animals. Most albinos find themselves at a disadvantage in life, since they don’t blend into their surroundings, and albino offspring in many species do not survive infancy. Snowy white polar bears, ptarmigans, artic foxes, and snowshoe hares, however, owe their camoflaging white coloring (and their very existence) to their albino ancestors.  Life creates by mistakes 7. Mutations – Genetik benzerlik: Good or Bad İnsan-İnsan %99.9 İnsan-Şempanze %96-99? İnsan-kedi %90 İnsan-köpek %30 İnsan-muz %60 ‘’Nature is, above all, profligate. Nature will try anything once. This is what sign of insect says. This is spendthrift economy; thougoh nothing is lost, all is spent. That insects have adapted is obvious. No form is too gruesome, no behavior is too grotesque.’’  3. The Work of Cells (What can a cell do?) Cells: 1. Are separated from the external environment by a surface membrane called Plasma or cell membrane. 2. Produce energy to drive many cellular processes: ATP 3. Produce their own external environment and glues: Extracellular matrix proteins, cell adherence molecules, and gap junctions 4. Change shape and move: Cytoskeletal filaments 5. Sense and Send Information: External and internal signals is transmitted. Regulate Their Gene Expression to Meet Changing Needs. 6. Grow and divide: Mitosis and Meiosis 7. May have also die, and programmed cell death: Apoptosis 1. Plasma Membrane 3. Animal Cells Produce Their Own External Environment and Glues. Collagen is a major component of the extracellular matrix in most tissues. 2. Cells Produce Energy To Drive 4. Cells Change Shape and Move Many Cellular Processes. ATP, the qThree types of protein filaments, universal “currency” of chemical organized into networks and bundles, form energy, the cytoskeleton within animal cells. All three fiber systems contribute to the shape and movements of cells. 5. Cells Sense And Send Information, 6. Cells Grow and Divide. Regulate gen expression. Eukaryotic Cell Cycle: During growth, The signals employed by cells include simple eukaryotic cells continually progress through small chemicals, gases, proteins, light, the cell cycle, generating new daughter cells, called mitosis. The eukaryotic cell cycle and mechanical movements. commonly is represented as four stages. It takes from 10–20 hours depending on cell type and developmental state. 7. Cells Die from Aggravated Assault or an Internal Program. In programmed cell death, called apoptosis, a dying cell actually produces proteins necessary for self-destruction. White blood cells (left).  4. Investigating Cells and Their Parts Investigating Cells and Their Parts is useful to: q Understand how the parts of a cell interact with one another, i.e., how they help to do the "work" of the cell. q Compare the factory to a cell, beginning to understand how both can be thought of as a system q Biologists are interested in objects ranging in size from small molecules to the tallest trees. qDevelopmental Biology Reveals Changes in the Properties of Cells as They Specialize q Choosing the Right Experimental Organism for the Job A sampling of biological objects aligned on a logarithmic scale. (a) The DNA double helix has a diameter of about 2 nm. (b) Eight-cell-stage human embryo three days after fertilization, about 200 um across. (c) A wolf spider, about 15 mm across. (d) Emperor penguins are about 1 m tall.  4. Investigating Cells and Their Parts Cell Biology Reveals the Size, Developmental Biology Reveals Shape, Changes in Genetics Reveals the and Location of Cell the Properties of Cells as They Consequences Components Specialize of Damaged Genes Genomics Reveals Differences in the Structure and Expression of Entire Genomes Differential gene expression can be detected in early fly embryos before cells are During the later stages of morphologically different. mitosis, microtubules (red) pull the replicated chromosomes (black) DNA microarray analysis gives toward the ends of a dividing Biochemistry Reveals the Molecular Structure a global cell. view of changes in and Chemistry of Purified transcription following Cell Constituents