11Biological BackgroundAmar MukherjeeSchool of Computer ScienceUniversity of Central Florida, OrlandoEmail: [email protected] and Molecular BiologyGenes Genes are discrete physical entities present in all living are discrete physical entities present in all living organisms that control hereditary characteristics passed from organisms that control hereditary characteristics passed from parents to offspring of organisms. parents to offspring of organisms. Study of heredity is called Study of heredity is called GeneticsGenetics. . GregorGregorMendel an Mendel an unknown monk in Brno (now in Czechoslovakia, it was in unknown monk in Brno (now in Czechoslovakia, it was in Austria ) published a paper in 1886 that pioneered the Austria ) published a paper in 1886 that pioneered the experimental study of genetics and his famous laws are called experimental study of genetics and his famous laws are called Mendel’s lawsMendel’s laws. Classical genetics assumed genes are . Classical genetics assumed genes are abstract attributes occurring in variant forms (called abstract attributes occurring in variant forms (called allelesalleles). ). Each individual inherits two genes, one from each of its Each individual inherits two genes, one from each of its parents.parents.In the 1930, it was recognized that like all particles in human In the 1930, it was recognized that like all particles in human body, genes must be composed of molecules and the field body, genes must be composed of molecules and the field devoted to understanding the chemical nature of genes was devoted to understanding the chemical nature of genes was termed termed molecular biologymolecular biology..23Biological InformationSoon biologists realized that genes are not merely units of inheritance but they are actually units of biological information that control all aspects of life –birth, growth, functioning as a living organism and death.Bioinformatics and Computational Molecular Biology are concerned with the use of computing and mathematical sciences as tools to advance traditional laboratory-based biology.The need to process an exponentially growing amount of biological information for further scientific advances and to understand its role in heredity, chemical processes within the cell, drug discovery, evolutionary studies etc. have created new problems that are of interdisciplinary nature. 4Protein or DNA• By 1920s, it was established that:– Genes reside on chromosomes– Chromosomes are made of protein and DNAChromosomes were discovered in 19thcentury as threadlike structures in the nucleus of a eukaryotic cell that could be observed under microscope as the cells begin to divide.Biochemical analysis concluded that chromosomes contain both DNA and protein. • The question was: What is the genetic material?–Protein?– DNA?– Both?The chemical structures of both DNA and protein were still unknown mysteries.35Properties of Genetic Material• Genetic Material:– Must be able to exist in almost infinite variety of forms– Protein was believed to be able to form long chains –macro molecules. Many proteins were known.– DNA was believed to be a small, invariant molecule.From the point of view of variability in species, proteins as carriers of genetic information seemed to make more sense. But this hypothesis was proved to be false by a famous experiment (by Griffith in 1942 and interpreted by Avery) that discovered a fundamental principle of Biology, called the Transforming Principle.6The Transforming Principle• Diplococcus pneumoniae exists in two forms:– Both the forms have a coating that surrounds the cell– The coating is made of a polysaccharide secreted by the bacterium– Each form secretes a different polysaccharide, hence a different coating & appearance.– The smooth (or S) form is virulent, whereas the rough(or R) form is avirulent.47Experiment (Griffith,Avery 1928)• Mouse injected with S form -> infected with pneumonia• Mouse injected with R form -> healthy• Mouse injected with heat-killed S form -> healthy• Mouse injected with heat-killed S bacteria + live R bacteria -> infected with pneumonia• Conclusion – a component (the genetic material) of heat-killed S-bacteria was able to enter R cell and transform them into smooth form. 8Eukaryote and Prokaryote Prokaryotes are the so-called ‘lower’ organisms which lack extensive cellular structures viz. membranes, organelles and the genetic material is not enclosed in a ‘nucleous’.Eukaryotes are organisms composed of one or many cells, each cell having a nucleous and a cytoplasm. This covers all living organisms except viruses and prokaryotes (bacteria and archea).Eukaryotes and prokaryotes diverged at the early stages of cell evolution.591061112ChromosomesOne of the threadlike "packages" of genes and other DNA in the nucleus of acell. Different kinds of organisms have different numbers of chromosomes. Humans have 23 pairs of chromosomes, 46 in all: 44 autosomes and two sexchromosomes. Each parent contributes one chromosome to each pair, so children get half of their chromosomes from their mothers and half fromtheir fathers We know now that DNA in chromosome carries the hereditary Information.The are also protein components in Chromosomes to package an enormouslylarge string of DNA into a compact shape that can fit inside of a cell.713The DNA for the Eukaryotes is distributed among the chromosomes. For example, the human genome has approximately 3.2 X109base pairs distributed over 24 chromosomes. Each chromosome is a long DNA packed very compactly with the help of a protein in the middle called Chromatin. In contrast , the bacteria carry their genes on a single DNA usually in circular form.14Eukaryotic Cell Division1. The chromosomes duplicate themselves and get themselves attached to spot called centromere.2. They thicken and shorten ( becomes visible under microscope now).3. The nuclear membrane dissolves and a fibrous spindle is formed, onthe chromosomes liner up.4. The centromeres divide, the spindle fibers tug the chromosome pairs apart.5. The chromosomes gather at opposite poles, the spindle disappears.6. The nuclear membreane re-formed, chromosomes, unwind, becomes invisible again and the two cells are formed.815Diploid and HaploidWe explained mitotic division in the previous slide. In higher organisms, haploid cells, each carrying one set of chromosomes, combine to produce diploid cells each carrying a