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Prepared with lots of help from friends... Metsada Pasmanik-Chor, Zohar Yakhini PowerPoint Presentation
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Prepared with lots of help from friends... Metsada Pasmanik-Chor, Zohar Yakhini

Prepared with lots of help from friends... Metsada Pasmanik-Chor, Zohar Yakhini

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Prepared with lots of help from friends... Metsada Pasmanik-Chor, Zohar Yakhini

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  1. BioInformatics / Computational Biology Introduction & Biological Terms. Prepared with lots of help from friends... Metsada Pasmanik-Chor, Zohar Yakhini and NUMEROUS WEB RESOURCES.

  2. 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.

  3. Prokaryotes vs. Eukaryotes One chromosome, (sometimes circular). http://departments.oxy.edu/biology/bio130/lectures_2000/11-13-00_lecture.htm

  4. 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.

  5. The Eukaryotic Cell cytoskeleton: * In plants: chloroplast & cell wall. http://www.biosci.uga.edu/almanac/bio_103/notes/may_15.html

  6. DNA - the Genetic Material • 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.dnaftb.org/dnaftb/9/concept/index.html http://www.accessexcellence.org/AE/AEPC/NIH/gene03.html

  7. 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

  8. Example: Tissues in Stomach • Cells originate from one embrio cell and have identical DNA. • Different cell types: Metabolism, regulation, function.

  9. http://www.dnaftb.org/dnaftb/17/animation/index.html

  10. DNA Structure control region telomere centromere gene - coding region • CONTROL REGIONS -Usually are adjacent to genes. • Determine when expressed, to what extend. • “JUNK DNA” -Unknown function.

  11. 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.

  12. A T C G Sugar Nucleotide ribose (RNA) deoxyribose (DNA) 4 DNA bases Pyrimidines Purines

  13. Watson-Crick Complementarity Conclusion: DNA strands are complementary (1953). % of each base Base ratios DNA source Human Sheep Turtle Sea urchin Wheat E. coli Purines/ Pyrimidines Pyrimidines Purines

  14. Watson-Crick Complementarity A binds to T C binds to G AATGCGTAGTC TTACGAATCAG AATGCTTAGTC TTACGAATCAG Perfect match One base mismatch

  15.  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). • 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 ! Human individuality http://www.brc.dcs.gla.ac.uk/~drg/seminars/bioinformatics/sld032.htm

  16. 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

  17. 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 ofintrons (splicing) occurs • RNA is very similar to DNA but has: • Only one strand. • Ribose as a sugar. • Uracil (U) instead of Thymine (T).

  18. 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 Gene exons splicing introns Transcription by RNA polymerase exons mRNA introns splicing www.albany.edu/~achm110/ mrna.gif

  19. Splicing - RNA Synthesis and Processing http://www1.imim.es/courses/Lisboa01/slide1.5_splicing.html

  20. Example of Alternative Splicing http://cbms.st-and.ac.uk/academics/ryan/Teaching/medsci/Medsci4.htm

  21. 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

  22. Genes can be turned ON and OFF http://www.dnaftb.org/dnaftb/33/concept/index.html

  23. Transcription Factors http://cbms.st-and.ac.uk/academics/ryan/Teaching/medsci/Medsci4.htm

  24. nitiationofranscriptionbyolymerasenitiationofranscriptionbyolymerase http://www1.imim.es/courses/Lisboa01/slide1.4_transcription.html

  25. Regulation of Expression promoter

  26. nucleus cytoplasm

  27. The Genetic Code: From 43 = 64 Codons to 20 AA. 4 nucleotide types 64 Codons 3 letter code 5’ 3’ 20 amino acids

  28. The Genetic Code: From 43 = 64 Codons to 20 AA. http://cbms.st-and.ac.uk/academics/ryan/Teaching/medsci/Medsci5.htm

  29. The Genetic Code The only start amino acid is Methionine, which has a single codon.

  30. http://cbms.st-and.ac.uk/academics/ryan/Teaching/medsci/Medsci4.htmhttp://cbms.st-and.ac.uk/academics/ryan/Teaching/medsci/Medsci4.htm

  31. Amino Acid Relative Frequencies- Mammals http://cbms.st-and.ac.uk/academics/ryan/Teaching/molbiol/Bioinf_files/v3_document.htm

  32. Nucleotides vs Amino Acids Code 5’ ACGTGTAGTTGCCGTGACG 3’ 3’ TGCACATCAACGGCACTGC 5’ A DNA sequence with direction shown N PKRGACMLTNQFKRKSACQ C A protein sequence with ends indicated

  33. Proteins

  34. Translation - Mediated by the ribosome, an organ which is made from rRNA and proteins.

  35. Proteins are Made of Amino Acids http://www.iacr.bbsrc.ac.uk/notebook/courses/guide/aa.htm

  36. 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

  37. Protein Structure http://www.yangene.com/content22_10.htm

  38. 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 ?

  39. Levels of Eukaryotic Gene Regulation http://www.library.csi.cuny.edu/~davis/Bioinfo_326/lectures/centralDogmaProteins/centralDogma.html

  40. Transcription Translation mRNA Protein Gene (DNA) Central Dogma DNA RNA Protein Symptomes (Phenotype) Cells express different subset of the genes in different tissues and under different conditions.

  41. The Central Dogma of Molecular Biology Replication- DNA duplication Transcription- RNA synthesis Nucleus Cytoplasm Translation- Protein synthesis http://www.accessexcellence.com/AB/GG/central.html

  42. New Central Dogma… 1 gene Many mRNA Transcripts due to alternative splicing Many protein types

  43. Central Dogma in the 21stCentury. 1 gene Many mRNA transcripts Many protein types http://www.nature.com/nrg/journal/v3/n1/slideshow/nrg703_bx1.html