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BioInformatics / Computational Biology Introduction & Biological Terms. Prepared with lots of help from friends... Metsada Pasmanik-Chor, Zohar Yakhini and NUMEROUS WEB RESOURCES. Outline • A Few Basic Concepts of Molecular Biology: • Genetic material - DNA & RNA. • DNA is a sequence of bases (A,C,T,G). • Watson-Crick–ery. • Proteins. • The central dogma of molecular biology. • Bio-Informatics Tools Freely available on the web: Highlights. Prokaryotes vs. Eukaryotes One chromosome, (sometimes circular). http://departments.oxy.edu/biology/bio130/lectures_2000/11-13-00_lecture.htm Cell Size and Shape 10-9 m All organisms are made of cells - basic unit of life (1014 cells in the human body; metabolism, replication). Cells in all organisms have same type ofgenetic material. The Eukaryotic Cell cytoskeleton: * In plants: chloroplast & cell wall. http://www.biosci.uga.edu/almanac/bio_103/notes/may_15.html DNA - the Genetic Material http://www.dnaftb.org/dnaftb/9/concept/index.html • Each human cell contains 23 pairs of chromosomes. • Chromosomes can be distinguished by size and by unique banding patterns. • This set is from a male, since it contains a Y chromosome. • Females have two X chromosomes. http://www.accessexcellence.org/AE/AEPC/NIH/gene03.html Different Eukaryotic Cell Types Different genes are activated in different cells, creating the specific proteins that give a particular cell type its character. http://www.accessexcellence.org/AE/AEPC/NIH/gene03.html Example: Tissues in Stomach • Cells originate from one embrio cell and have identical DNA. • Different cell types: Metabolism, regulation, function. http://www.dnaftb.org/dnaftb/17/animation/index.html DNA Structure telomere control region centromere gene coding region • • CONTROL REGIONS - Usually are adjacent to genes. Determine when expressed, to what extend. “JUNK DNA” - Unknown function. DNA - (deoxyribonucleic acid THE Double Helix) Source: Alberts et al DNA is made of 4 subunits (nucleotides). Each nucleotide contains: sugar, phosphate group and a base. A C T G Nucleotide Sugar ribose (RNA) deoxyribose (DNA) 4 DNA bases Purines Pyrimidines Watson-Crick Complementarity Conclusion: DNA strands are complementary (1953). Base ratios % of each base DNA source Human Sheep Turtle Sea urchin Wheat E. coli Purines/ Pyrimidines Pyrimidines Purines Watson-Crick Complementarity A binds to T C binds to G AATGCTTAGTC TTACGAATCAG AATGCGTAGTC TTACGAATCAG Perfect match One base mismatch Variability - facts • Genes carry the instructions for cellular proteins. • Variations in the code is the source for cellular variations. • Disease and susceptibility to disease can be caused by changes in the DNA (mutations). Human individuality • DNA is identical in all cells of an individual, almost identical among different individuals of same species (99.9%), and very similar in related species (human vs chimpanzee - 98% identity). • Only 3% of cellular DNA has a known function ! http://www.brc.dcs.gla.ac.uk/~drg/seminars/bioinformatics/sld032.htm Hereditary mutations: Carried in the DNA of the reproductive cells. The mutation will be present in all of the offspring's body cells. Acquired mutations: Developed in the DNA during a person's lifetime. If the mutation arises in a body cell, copies of the mutation will exist only in descendants of that particular cell. http://www.accessexcellence.org/AE/AEPC/NIH/gene07.html RNA - ribonucleic acid Some viruses store genetic information in form of RNA. In eukaryotes, RNA is formed from DNA in a process called transcription where elimination of introns (splicing) occurs RNA is very similar to DNA but has: • Only one strand. • Ribose as a sugar. • Uracil (U) instead of Thymine (T). Splicing - RNA Synthesis and Processing The seven green loops stand for introns The eight blue bands stand for exons Chromosomal DNA Mature mRNA Poly A tail Stop signal Promoter/enhancer exons splicing Gene introns Transcription by RNA polymerase exons mRNA www.albany.edu/~achm110/ mrna.gif introns splicing Splicing - RNA Synthesis and Processing http://www1.imim.es/courses/Lisboa01/slide1.5_splicing.html Example of Alternative Splicing http://cbms.st-and.ac.uk/academics/ryan/Teaching/medsci/Medsci4.htm Types of RNA mRNA - A copy of a gene (without introns), encoding protein sequence. Used in translation: tRNA - Small RNA, serves as “adaptor” between mRNA and amino acids. rRNA - One of the structural components of the ribosome (the translation machine from mRNA to proteins). http://www.dnaftb.org/dnaftb/24/concept/index.html See animation at: http://www.dnaftb.org/dnaftb/21/animation/index.html Genes can be turned ON and OFF http://www.dnaftb.org/dnaftb/33/concept/index.html Transcription Factors http://cbms.st-and.ac.uk/academics/ryan/Teaching/medsci/Medsci4.htm nitiation of ranscription by olymerase http://www1.imim.es/courses/Lisboa01/slide1.4_transcription.html Regulation of Expression promoter The Genetic Code: From 43 = 64 Codons to 20 AA. 4 nucleotide types 3 letter code 5’ 3’ 64 Codons 20 amino acids The Genetic Code: From 43 = 64 Codons to 20 AA. http://cbms.st-and.ac.uk/academics/ryan/Teaching/medsci/Medsci5.htm The Genetic Code The only start amino acid is Methionine, which has a single codon. http://cbms.st-and.ac.uk/academics/ryan/Teaching/medsci/Medsci4.htm Amino Acid Relative FrequenciesMammals http://cbms.st-and.ac.uk/academics/ryan/Teaching/molbiol/Bioinf_files/v3_document.htm Nucleotides vs Amino Acids Code 5’ 3’ ACGTGTAGTTGCCGTGACG TGCACATCAACGGCACTGC 3’ 5’ A DNA sequence with direction shown N PKRGACMLTNQFKRKSACQ C A protein sequence with ends indicated Proteins Translation - Mediated by the ribosome, an organ which is made from rRNA and proteins. Proteins are Made of Amino Acids http://www.iacr.bbsrc.ac.uk/notebook/courses/guide/aa.htm Translation in Eukaryotes http://www1.imim.es/courses/Lisboa01/slide1.6_translation.html Animation: http://cbms.st-and.ac.uk/academics/ryan/Teaching/medsci/Medsci6.htm Protein Structure http://www.yangene.com/content22_10.htm What Determines Cell Structure and Function ? • Unique protein expression by each cell type. • Proteins are ~60% of dry mass of living cell. • Proteins determine function. How is this controlled ? Levels of Eukaryotic Gene Regulation http://www.library.csi.cuny.edu/~davis/Bioinfo_326/lectures/centralDogmaProteins/centralDogma.html Central Dogma Transcription Translation mRNA Gene (DNA) DNA RNA Cells express different subset of the genes in different tissues and under different conditions. Protein Protein Symptomes (Phenotype) The Central Dogma of Molecular Biology ReplicationDNA duplication Nucleus TranscriptionRNA synthesis Cytoplasm TranslationProtein synthesis http://www.accessexcellence.com/AB/GG/central.html New Central Dogma… 1 gene Many mRNA Transcripts due to alternative splicing Many protein types Central Dogma in the 21st Century. 1 gene Many mRNA transcripts Many protein types http://www.nature.com/nrg/journal/v3/n1/slideshow/nrg703_bx1.html