Computational Biology Unit 1 2024 PDF

UNIT 1 ▪Introduction ▪Cell theory ▪Whitaker’s kingdom classification ▪Cell organelles, and their functions ▪Homeostasis ▪Replication and cell Division ▪Tissue differentiation ▪Stem cells and their applications ▪Genetic algorithms Introduction 2  Con...

UNIT 1 ▪Introduction ▪Cell theory ▪Whitaker’s kingdom classification ▪Cell organelles, and their functions ▪Homeostasis ▪Replication and cell Division ▪Tissue differentiation ▪Stem cells and their applications ▪Genetic algorithms Introduction 2  Concept of evolution The process by which different kinds of living organism are believed to have developed from earlier forms during the history of the earth. Evolution is the change in the heritable characteristics of biological populations over successive generations. Jean Baptistae Lamarck (1801)-spontaneous generation of species according to needs and functionalities of the mutation Charles darwin (1859)- Based on survival of the fittest mutations 3 Cell theory 4  Living Organism A living organism may be defined as a complex unit of physicochemical materials that is capable of self- regulation, metabolism, and reproduction. Furthermore, a living organism demonstrates the ability to interact with its environment, grow, move, and adapt. 5 What Are the main characteristics of organisms?  Made of cells  Require energy (food)  Reproduce (species)  Maintain homeostasis  Organized  Respond to environment  Grow and develop  Exchange materials with surroundings (water, wastes, gases) 6  Cell - Basic unit of life a. Smallest living form b. Inside the cell some structure transport c. Metabolize d. Respire e. Reproduce (Meiosis) f. Multiply (Mitosis) g. Energy producing h. Keep information 7  Prokaryotes Nucleoid region (center) contains the DNA Surrounded by cell membrane & cell wall (peptidoglycan) Contain ribosomes (no membrane) in their cytoplasm to make proteins 8  Eukaryotes Cells that have a nucleus and membrane-bound organelles Includes protists, fungi, plants, and animals More complex type of cells 9  CELL THEORY Suggested by German scientists Theodor Schwann and Matthias Jakob Schleiden in 1838 Matthias Schleiden, a German botanist, and Theodor Schwann, a British Zoologist formulated the cell theory All living things are made of cells Cells are the basic unit of structure and function in an organism (basic unit of life) Cells come from the reproduction of existing cells (cell division) 10 Whittaker’s five kingdom of Classification 11  Five Kingdoms and their chief characteristics Unicellular organisms that lack a nucleus and many of the specialized cell parts, called organelles. Such organisms are said to be prokaryotic (pro =‘‘before’’; karyotic =‘‘kernel,’’ ‘‘nucleus’’) and consist of bacteria. All of the other kingdoms consist of eukaryotic (eu = ‘‘true’’) organisms, which have cells that contain a nucleus and a fuller repertory of organelles. 12 Five Kingdoms and their chief characteristics 13 14 Cell Structure and Function 15  Organelles Very small (Microscopic) Perform various functions for a cell Found in the cytoplasm May or may not be membrane-bound Plant Cell 16  Cell or Plasma Membrane Composed of double layer of phospholipids and proteins Surrounds outside of all cells Controls what enters or leaves the cell Living layer Outside of cell Carbohydrate Proteins chains Cell membrane Inside of cell Protein Lipid bilayer (cytoplasm) channel 17  Cytoplasm of a Cell cytoplasm Jelly-like substance enclosed by cell membrane Provides a medium for chemical reactions to take place Contains organelles to carry out specific jobs Found in all cells 18  The Control Organelle - Nucleus Controls the normal activities of the cell Contains the DNA in chromosomes Bounded by a nuclear envelope (membrane) with pores Usually the largest organelle Each cell has fixed number of chromosomes that carry genes 19  Nucleolus Inside nucleus Cell may have 1 to 3 nucleoli Disappears when cell divides Makes ribosomes that make proteins 20  Cytoskeleton Helps cell maintain cell shape Also help move organelles around Made of proteins Microfilaments are threadlike & made of ACTIN Microtubules are tube-like and made of TUBULIN Cytoskeleton Microtubules Microfilaments 21  Centrioles Found only in animal cells Paired structures near nucleus Made of bundle of microtubules Appear during cell division forming mitotic spindle Help to pull chromosome pairs apart to opposite ends of 22 the cell  Mitochondrion (plural = mitochondria) “Powerhouse” of the cell Generate cellular energy (ATP) More active cells like muscle cells have more mitochondria Both plants & animal cells have mitochondria Site of cellular respiration (burning glucose) 23  Mitochondria Surrounded by a double membrane Has its own DNA – Mitochondria come from cytoplasm in the egg cell during fertilization – Therefore you inherit your mitochondria from your mother! Folded inner membrane called cristae (increases surface area for more chemical reactions) Interior called matrix 24  Endoplasmic Reticulum - ER Network of hollow membrane tubules Connects to nuclear envelope & cell membrane Functions in synthesis of cell products & transport 25 Two kinds of ER ---Rough & Smooth Rough Endoplasmic Reticulum (Rough ER) Has ribosomes on its surface Makes membrane proteins and proteins for export out of cell Proteins are made by ribosomes on ER surface They are then threaded into the interior of the Rough ER to be modified and transported 26  Smooth Endoplasmic Reticulum Smooth ER lacks ribosomes on its surface Is attached to the ends of rough ER Makes cell products that are used inside the cell Makes membrane lipids (steroids) Regulates calcium (muscle Includes nuclear membrane cells) connected to ER connected Destroys toxic substances to cell membrane (transport) (Liver) 27  Ribosomes Made of proteins and rRNA “Protein factories” for cell Join amino acids to make proteins Process called protein synthesis Can be attached to Rough ER OR Be free (unattached) in the cytoplasm 28  Golgi Bodies Stacks of flattened sacs Have a shipping side (trans face) and CIS receiving side (cis face) Receive proteins made by ER Transport vesicles with modified proteins TRANS pinch off the ends Transport vesicle 29  Golgi Bodies  Look like a stack of pancakes  Modify, sort, & package molecules from ER for storage or transport out of the cell. 30  Lysosomes Contain digestive enzymes Break down food, bacteria, and worn out cell parts for cells Programmed for cell death (Autolysis) Lyse (break open) & release enzymes to break down & recycle cell parts) 31  Lysosome Digestion Cells take in food by phagocytosis Lysosomes digest the food & get rid of wastes 32  Vacuoles Fluid filled sacks for storage Small or absent in animal cells Plant cells have a large Central Vacuole No vacuoles in bacterial cells In plants, they store Cell Sap Includes storage of sugars, proteins, minerals, lipids, wastes, salts, water, and enzymes 33  Chloroplasts Found only in producers (organisms containing chlorophyll) Use energy from sunlight to make own food (glucose) Energy from sun stored in the Chemical Bonds of Sugars 34  Surrounded by double membrane  Outer membrane smooth  Inner membrane modified into sacs called thylakoids  Thylakoids in stacks called Grana & interconnected  Stroma – gel like material surrounding thylakoids 35  Chloroplasts Contains its own DNA Contains enzymes & pigments for Photosynthesis Never in animal or bacterial cells Photosynthesis – food making process 36 Homeostasis 37  Homeostasis Definition : Maintenance of the relative stability of the physical and chemical aspects of the internal environment within a range compatible with cellular function. Maintaining a constant internal environment with all that the cells need to survive (O2, glucose, minerals, ions, and waste removal) is necessary for individual cells. The processes by which the body regulates its internal environment are referred to as homeostasis. Components : 1) sensor 2) afferent pathway 3) integration center or comparator 4) efferent pathway 5) effector organ(s) Physiological control systems are the nervous system, endocrine system, and immune system through feedback mechanisms. 38 39  Extrinsic homeostatic systems Nervous System The nervous system maintains homeostasis by controlling and regulating the other parts of the body. – A deviation from a normal set point acts as a stimulus to a receptor, which sends nerve impulses to a regulating center in the brain. The brain directs an effector to act in such a way that an adaptive response takes place. The nervous system has two major portions: the central nervous system and the peripheral nervous system. 40 Classification of Nervous System 41  Regulating centers are located in the central nervous system, consisting of the brain and spinal cord. – The hypothalamus is a portion of the brain particularly concerned with homeostasis; it influences the action of the medulla oblongata, a lower part of the brain, the autonomic nervous system, and the pituitary gland. The peripheral nervous system consists of the spinal nerves. The autonomic nervous system is a part of peripheral nervous system and contains motor neurons that control internal organs. It has two divisions, the sympathetic and parasympathetic systems. 42 43  Endocrine System The endocrine system consists of glands which secrete special compounds called hormones into the bloodstream. Each hormone has an effect on one or more target tissues. In this way the endocrine system regulates the metabolism and development of most body cells and body systems. For e.g. the endocrine system has sex hormones that can activate sebaceous glands, development of mammary glands, alter dermal blood flow, and release lipids from adipocytes etc. besides governing reproduction. 44 Endocrine System 45  In the muscular system, hormones adjust muscle metabolism, energy production, and growth. In the nervous system, hormones affect neural metabolism, regulate fluid/electrolyte balance and help with reproductive hormones that influence CNS (central nervous system), development and behaviors. In the cardiovascular system, hormones regulate heart rate and blood pressure. Hormones also have anti-inflammatory effects and control the lymphatic system. 46  Negative feedback : a control system that causes the value of a physiological measurement to change in the direction opposite to the initial deviation from set point. 47  Positive feedback : a control system that causes the value of a physiological measurement to change in the same direction as the initial deviation from set point. 48 Cell growth, reproduction, and differentiation 49  The Cell Cycle Mitosis and meiosis are single steps in cell cycle G1, S, G2, and M phases – Cells not in process of dividing are in G0 phase – Chromosomes are duplicated in preparation for the next round of division during interphase 50 51  Control of the Cell Cycle The stimuli for entering the cell cycle is in the form of growth factors and cytokines that are capable of inducing mitotic divisions The cell cycle is highly regulated – Proteins whose concentrations rise & fall in a controlled manner Cyclin and cyclin-dependent kinases (cdk) p53 and pRb Inhibitors of cdk Internal checkpoints & guardians monitor cell health Errors in this process can lead to uncontrollable growth and cancer 52  Control of the Cell Cycle Cell cycle control is focused at 3 places: G1 checkpoint G2 checkpoint M checkpoint – Before S phase (DNA synthesis) – At transition between G2 and M phase 53  DNA replication-Binary fission Daughter cells are identical copies Chromoso Plasma me membrane (1 (2 (3 ) ) ) (4 (5 (6 ) ) ) Neither mitosis nor meiosis occurs in prokaryotes 54  DNA Bacteria Reproduction cell wall Asexual, through binary fission No true sexual reproduction, since neither mitosis nor meiosis exist in prokaryotes Horizontal transfer of genetic material  Transformation - Uptake of genetic material from the environment  Transduction - Transfer of genetic material between prokaryotes by viruses  Conjugation - Direct transfer of genetic material from one prokaryote to another 56  Mitosis Four phases – a. Prophase: chromosomes condense, spindle apparatus forms, nuclear envelope breaks down b. Metaphase: chromosomes line up at equator of cell c. Anaphase: sister chromatids separate d. Telophase: new nuclear envelopes form, chromosomes unwind 57  pair of homologous, duplicated chromosomes sister chromatids of nuclear one duplicated envelope homologue 58 59 (a) Interphase in a seed cell: The (b) Late prophase: The (c) Metaphase: The chromosomes chromosomes (blue) are in the chromosomes (blue) have have moved to the equator of the thin, extended state and appear condensed and attached to cell. as a mass in the center of the the spindle microtubules (red). cell. The spindle microtubules (red) extend outward from the nucleus to all parts of the cell. (d) Anaphase: Sister (e) Telophase: The (f) Resumption of interphase: The chromatids chromosomes have gathered chromosomes are relaxing again have separated, and one set into two clusters, one at the into their extended state. The spindle has moved toward each pole. site of each future nucleus. microtubules are disappearing, and the microtubules of the two 60 daughter cells are rearranging into the interphase pattern. Each new nucleus is genetically identical to the parent nucleus Daughter Cells Each cell has the same Parent Cell genetic makeup as the Chromosomes parent cell have been replicated Mitosis 61  Mitosis or Somatic Cell Division A cell divides producing two genetically identical daughter cells. New cells are produced for growth or repair of aging or damaged tissues. For asexual reproduction 62 Interphase The stage between two successive cell divisions. Prior to mitosis, thin strands of DNA in a cell thicken into chromosomes, which then duplicate 63 Early Prophase The centrioles divide and with the asters, move apart The nuclear membrane begins to disintegrate Late Prophase The centrioles and asters are pushed to the opposite poles of the cell. Spindle fibers extend between the poles The nuclear membrane and nucleolus have almost disappeared 64 Metaphase Nuclear membrane disappears completely The double chromosomes, their centromeres attached to the spindle fibers, align at the metaphase plate, midline of the cell. 65 Early Anaphase The centromeres split half moving to one pole and half to the other pole Late Anaphase The chromosomes have almost reached to their respective poles. The cell membrane begins to contract at the midline. 66 Telophase The cell membrane completes contraction, closing over to split the cell in two. Nuclear membrane form around the chromatin masses within each new daughter cell. Mitosis completed There are now two cells, with structures and chromosomes identical to each other and the original cell  Meiosis Characteristics of meiosis -  Occurs in sex cells (germ cells) and produces gametes.  A reduction division resulting in haploid cells.  Involves two sequential divisions resulting in four cells.  Produces cells that are genetically different because of genetic recombination (crossing-over). 68  Meiosis produces gametes for sexual reproduction Multiplies number of cells but also reduces chromosome number in each daughter cell to exactly half the number present before meiosis Daughter cells get 1 member of each homologous pair, i.e. 1 allele for each gene Mitosis produces 2 daughter cells Meiosis produces 4 daughter cells All body cells in humans are diploid, except gametes Cells with 1 member of each homologous pair are haploid 69  Meiosis Daughter Cells (1n) Gamete Cells (1n) each chromosome has 2 chromatids Parent Cell (2n) 1st division 2nd division 70 71 72 73  Cell Differentiation The process of altering the pattern of gene expression and thus becoming a cell of a particular type is called cell differentiation. Presence of chemicals (or other influences) starts altering the decisions as to which genes will be turned on or off. The zygote is a totipotent cell - its daughter cells can become any cell type. As the development proceeds, some of the cells become pluripotent - they can become many, but not all cell types. Later on, the specificity narrows down further and a particular stem cell can turn into only a very limited number of cell types, e.g., a few types of blood cells, but not bone or brain cells or anything else. That is why embryonic stem cell research is much more promising than the adult stem cell research. 74 75 Differentiation of different tissues and organs 76 Differentiation of different tissues and organs 77 Stem cells and their applications 78 79 80 81 82 83 84 85 86 87 Genetic Algorithm 88  Genetic Algorithms Genetic algorithms (GA) in programming, simulate the process of natural selection which means those species who can adapt to changes in their environment are able to survive and reproduce and go to next generation. In simple words, they simulate “survival of the fittest” among individual of consecutive generation for solving a problem. Genetic algorithms are based on an analogy with genetic structure and behavior of chromosomes of the population. 89 Following is the foundation of GAs based on this analogy – 1. Individual in population compete for resources and mate 2. Those individuals who are successful (fittest) then mate to create more offspring than others 3. Genes from “fittest” parent propagate throughout the generation, that is sometimes parents create offspring which is better than either parent. 4. Thus each successive generation is more suited for their environment. 90 91  Components of a search space in Genetic algorithm Gene represents a single solution to a problem chromosome (individual) is composed of several genes or multiple similar solutions. population of individuals are maintained within search space - all solutions to the problem The whole algorithm can be summarized as – ‾ Randomly initialize n populations ‾ Determine fitness of population ‾ Until convergence repeat: a) Select parents from population b) Crossover and generate new population c) Perform mutation on new population d) Calculate fitness for new population 92  The Fitness score The GAs maintains the population of n individuals (chromosome/solutions) along with their fitness scores. The individuals having better fitness scores are given more chance to reproduce than others. The individuals with better fitness scores are selected who mate and produce better offspring by combining chromosomes of parents. Always the new generation of solutions will have better fitness than the parent population. 93  Operators for GA The Algorithm uses certain biological concepts as operators to find better solutions Cross Over Crossover Mutation Selection ( best fitness score in previous generation) Mutation 94  Uses of GA Genetic Algorithms are primarily used in optimization problems of various kinds, but they are frequently used in other application areas. Optimization − Genetic Algorithms are most commonly used in optimization problems wherein we have to maximize or minimize a given objective function value under a given set of constraints. DNA Analysis − GAs have been used to determine the structure of DNA using spectrometric data about the sample. 95  Neural Networks − GAs are also used to train neural networks, particularly recurrent neural networks. Parallelization − GAs also have very good parallel capabilities, and prove to be very effective means in solving certain problems, and also provide a good area for research. 96  Advantages of GA Does not require any derivative information (which may not be available for many real-world problems). Is faster and more efficient as compared to the traditional methods. Provides a list of “good” solutions and not just a single solution. 97  Disadvantages of GA GAs are not suited for all problems, especially problems which are simple and for which derivative information is available. Fitness value is calculated repeatedly which might be computationally expensive. Being stochastic, there are no guarantees on the optimality or the quality of the solution. 98 Thank you 99