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Challenges in BioinformaticsPart I
Vasileios Hatzivassiloglou
University of Texas at Dallas
Evolution timeline
• Earth forms (4.5 billion years ago)
• Earth acquires solid crust (4.1 by)
• First life form, self-replicating RNA (4 by); no oxygen in the atmosphere
• First bacteria and archaea (3.9 by)
• Photosynthesis in bacteria (3.5 by)
• First eukaryotes (2.1 by)
• Sexual reproduction (1.2 by)
Evolution timeline, part II
• First multicellular organisms (algae and seaweeds, 1 by)
• Sponges, jellyfish, worms (600 my)• First fish (500 my)• First plants on land (475 my)• Arthropods on land (450 my)• First insects (400 my)• Seeds in plants, amphibians (350 my)• Pangaea, First reptiles (300 my)
Evolution timeline, part III
• Crocodiles, first dinosaurs (250 my)
• Giant dinosaurs (150 my)
• First flowers (130 my)
• First ancenstor of mice and humans (100 my)
• Dinosaurs extinct, mammals dominate (65 my)
• First primates (55 my)
Evolution timeline, part IV
• Earliest humans (homo habilis, erectus; 2 my)
• Homo sapiens (140,000 years ago)– population reaches 5 million 11,000 years ago– 150 million 2,000 years ago– 6 billion 6 years ago– 6.7 billion as of July 2008
Interactive evolution timeline
• Online at http://www.johnkyrk.com/evolution.swf
A familiar organism• Kingdom: Animalia• Phylum: Chordata • Subphylum: Vertebrata • Class: Mammalia • Order: Primates • Suborder: Anthropoidea • Superfamily: Hominoidea • Family: Hominidae • Genus: Homo • Species: Homo sapiens• Subspecies: Homo sapiens sapiens
Hominid species
What kind of biology?
• Biochemistry– lowest level, studies chemical substances and
interactions
• Molecular biology– gene/protein interactions, structure, and
function– molecular genetics– proteomics
What kind of biology?
• Cellular biology
• Histology / physiology / anatomy– studies multi-cell groups
• Developmental biology– cell growth, morphogenesis
• Genetics– mechanisms of heredity and variation
• Evolutionary biology
Human migration
• Based on– fossil record– study of mtDNA (mitochondrial DNA)– mtDNA better suited to tracking generations
• more mutations• more copies• inherited only through the mother
Identification through mtDNA
Jesse James (1847-1882)
Notorious outlaw in Missouri
Stone AC, Starrs JE, Stoneking, M. Mitochondrial DNA analysis of the presumptive remains of Jesse James. J of Forensic Sci 2001; 46(1):173–176.
Human migration animation
• Online animation at http://www.bradshawfoundation.com/journey/timeline.swf
Problems in Bioinformatics
• Overview of major topics in bioinformatics
• What the problem is
• Elements of the solution
• Computational issues
Sequencing
• Find the sequence of nucleotides• A genome must be sequenced in small
parts (~1000 bp)• For each part, given fragments of a DNA
sequence (e.g., matches via a DNA chip), assemble the entire fragment in the correct order
• Reassemble the parts– an NP-hard problem
Polymerase chain reaction (PCR)
• A general method for amplifying DNA (or RNA via reverse transcription)
• In vitro technique (as opposed to in vivo)• Uses DNA polymerase to simulate
replication, and primers (10-45 bp) as start and end markers
• Proceeds in cycles; can amplify fragments up to 10kb long (sometimes 50kb)
• Invented in 1983, Nobel prize in 1993
Applications of PCR
• Chain reaction (Sanger) sequencing• Genetic fingerprinting
– Forensics– Paternity tests
• Detection of hereditary diseases• Cloning of genes• Gene modification (mutagenesis)
– directed versus random– production of recombinant DNA (rDNA)
Sample DNA fingerprint
(1) Father
(2) Child
(3) Mother
Zebra fish
Recombinant DNA on zebra fish
• Insert an additional gene that changes color and causes fluorescence
• Added gene comes from jellyfish (green, yellow) or sea coral (red)
• Developed in 1999 in Singapore / Taiwan• Purpose: Detect pollution by making
fluorescence activated by toxins• Group of Texas entrepreneurs markets the
fish for aquariums (2002)
GloFishTM