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A short introduction to biology

A short introduction to biology. Life. Two categories: Prokaryotes (e.g. bacteria) Unicellular No nucleus Eukaryotes (e.g. fungi, plant, animal) Unicellular or multicellular Has nucleus. Prokaryote vs Eukaryote. Eukaryote has many membrane-bounded compartment inside the cell

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A short introduction to biology

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  1. A short introduction to biology

  2. Life • Two categories: • Prokaryotes (e.g. bacteria) • Unicellular • No nucleus • Eukaryotes (e.g. fungi, plant, animal) • Unicellular or multicellular • Has nucleus

  3. Prokaryote vs Eukaryote • Eukaryote has many membrane-bounded compartment inside the cell • Different biological processes occur at different cellular location

  4. Organ Organism, Organ, Cell Organism

  5. Chemical contents of cell • Water • Macromolecules (polymers) - “strings” made by linking monomers from a specified set (alphabet) • Protein • DNA • RNA • … • Small molecules • Sugar • Ions (Na+, Ka+, Ca2+, Cl- ,…) • Hormone • …

  6. DNA • DNA: forms the genetic material of all living organisms • Can be replicated and passed to descendents • Contains information to produce proteins • To computer scientists, DNA is a string made from alphabet {A, C, G, T} • e.g. ACAGAACGTAGTGCCGTGAGCG • Each letter is a nucleotide • Length varies from hundreds to billions

  7. RNA • Historically thought to be information carrier only • DNA => RNA => Protein • New roles have been found for them • To computer scientists, RNA is a string made from alphabet {A, C, G, U} • e.g. ACAGAACGUAGUGCCGUGAGCG • Each letter is a nucleotide • Length varies from tens to thousands

  8. Protein • Protein: the actual “worker” for almost all processes in the cell • Enzymes: speed up reactions • Signaling: information transduction • Structural support • Production of other macromolecules • Transport • To computer scientists, protein is a string made from 20 kinds of characters • E.g. MGDVEKGKKIFIMKCSQCHTVEKGGKHKTGP • Each letter is called an amino acid • Length varies from tens to thousands

  9. DNA/RNA zoom-in • Commonly referred to as Nucleic Acid • DNA: Deoxyribonucleic acid • RNA: Ribonucleic acid • Found mainly in the nucleus of a cell (hence “nucleic”) • Contain phosphoric acid as a component (hence “acid”) • They are made up of a string of nucleotides

  10. Nucleotides • A nucleotide has 3 components • Sugar ring (ribose in RNA, deoxyribose in DNA) • Phosphoric acid • Nitrogen base • Adenine (A) • Guanine (G) • Cytosine (C) • Thymine (T) in DNA and Uracil (U) in RNA

  11. A G C G A C T G 5’ Free phosphate 5 prime 3 prime 5’-AGCGACTG-3’ AGCGACTG DNA Often recorded from 5’ to 3’, which is the direction of many biological processes. e.g. DNA replication, transcription, etc. Base 5 Phosphate Sugar 4 1 2 3 3’

  12. A G U G A C U G 5’ Free phosphate 5 prime 3 prime 5’-AGUGACUG-3’ AGUGACUG RNA Often recorded from 5’ to 3’, which is the direction of many biological processes. e.g. translation. Base 5 Phosphate Sugar 4 1 2 3 3’

  13. A T G C C G G C A T C G A T G C 3’ 5’ Base-pair: A = T G = C Forward (+) strand 5’-AGCGACTG-3’ 3’-TCGCTGAC-5’ Backward (-) strand AGCGACTG TCGCTGAC One strand is said to be reverse- complementary to the other 3’ 5’ DNA usually exists in pairs.

  14. DNA double helix G-C pair is stronger than A-T pair

  15. RNA • RNAs are normally single-stranded • Form complex structure by self-base-pairing • A=U, C=G • Can also form RNA-DNA and RNA-RNA double strands. • A=T/U, C=G

  16. Carboxyl group Amino group Protein zoom-in • Protein is the actual “worker” for almost all processes in the cell • A string built from 20 kinds of chars • E.g. MGDVEKGKKIFIMKCSQCHTVEKGGKH • Each letter is called an amino acid R | H2N--C--COOH | H Side chain Generic chemical form of amino acid

  17. Units of Protein: Amino acid • 20 amino acids, only differ at side chains • Each can be expressed by three letters • Or a single letter: A-Y, except B, J, O, U, X, Z • Alanine = Ala = A • Histidine = His = H

  18. Amino acids => peptide R R | | H2N--C--COOH H2N--C--COOH | | H H R R | | H2N--C--CO--NH--C--COOH | | H H Peptide bond

  19. R R R R R R … H2N COOH C-terminal N-terminal Protein • Has orientations • Usually recorded from N-terminal to C-terminal • Peptide vs protein: basically the same thing • Conventions • Peptide is shorter (< 50aa), while protein is longer • Peptide refers to the sequence, while protein has 2D/3D structure

  20. Genome and chromosome • Genome: the complete DNA sequences in the cell of an organism • May contain one (in most prokaryotes) or more (in eukaryotes) chromosomes • Chromosome: a single large DNA molecule in the cell • May be circular or linear • Contain genes as well as “junk DNAs” • Highly packed!

  21. Formation of chromosome

  22. Formation of chromosome 50,000 times shorter than extended DNA The total length of DNA present in one adult human is the equivalent of nearly 70 round trips from the earth to the sun

  23. Gene • Gene: unit of heredity in living organisms • A segment of DNA with information to make a protein or a functional RNA

  24. Some statistics

  25. Human genome • 46 chromosomes: 22 pairs + X + Y 1 from mother, 1 from father • Female: X + X • Male: X + Y

  26. Central dogma of molecular biology

  27. DNA Replication • The process of copying a double-stranded DNA molecule • Semi-conservative 5’-ACATGATAA-3’ 3’-TGTACTATT-5’  5’-ACATGATAA-3’ 5’-ACATGATAA-3’ 3’-TGTACTATT-5’ 3’-TGTACTATT-5’

  28. p p p Nucleotide triphosphate (dNTP) • Mutation: changes in DNA base-pairs • Proofreading and error-correcting mechanisms exist to ensure extremely high fidelity

  29. Central dogma of molecular biology

  30. Transcription • The process that a DNA sequence is copied to produce a complementary RNA • Called message RNA (mRNA) if the RNA carries instruction on how to make a protein • Called non-coding RNA if the RNA does not carry instruction on how to make a protein • Only consider mRNA for now • Similar to replication, but • Only one strand is copied

  31. Transcription (where genetic information is stored) • DNA-RNA pair: • A=U, C=G • T=A, G=C (for making mRNA) Coding strand: 5’-ACGTAGACGTATAGAGCCTAG-3’ Template strand: 3’-TGCATCTGCATATCTCGGATC-5’ mRNA: 5’-ACGUAGACGUAUAGAGCCUAG-3’ Coding strand and mRNA have the same sequence, except that T’s in DNA are replaced by U’s in mRNA.

  32. Translation • The process of making proteins from mRNA • A gene uniquely encodes a protein • There are four bases in DNA (A, C, G, T), and four in RNA (A, C, G, U), but 20 amino acids in protein • How many nucleotides are required to encode an amino acid in order to ensure correct translation? • 4^1 = 4 • 4^2 = 16 • 4^3 = 64 • The actual genetic code used by the cell is a triplet. • Each triplet is called a codon

  33. The Genetic Code Third letter

  34. Translation • The sequence of codons is translated to a sequence of amino acids • Gene: -GCT TGT TTA CGA ATT- • mRNA: -GCUUGUUUACGAAUU - • Peptide: - Ala - Cys - Leu - Arg - Ile – • Start codon: AUG • Also code Met • Stop codon: UGA, UAA, UAG

  35. Translation • Transfer RNA (tRNA) – a different type of RNA. • Freely float in the cell. • Every amino acid has its own type of tRNA that binds to it alone. • Anti-codon – codon binding crucial. tRNA-Pro Anti-codon Nascent peptide tRNA-Leu mRNA

  36. Transcriptional regulation • Will talk more in later lectures • RNA polymerase binds to certain location on promoter to initiate transcription • Transcription factor binds to specific sequences on the promoter to regulate the transcription • Recruit RNA polymerase: induce • Block RNA polymerase: repress • Multiple transcription factors may coordinate Transcription factor RNA Polymerase Transcription starting site gene promoter

  37. Splicing Transcription starting site • Pre-mRNA needs to be “edited” to form mature mRNA • Will talk more in later lectures. gene promoter transcription Pre-mRNA intron intron Pre-mRNA exon exon exon 3’ UTR 5’ UTR Splicing Mature mRNA (mRNA) Open reading frame (ORF) Start codon Stop codon

  38. Summary • DNA: a string made from {A, C, G, T} • Forms the basis of genes • Has 5’ and 3’ • Normally forms double-strand by reverse complement • RNA: a string made from {A, C, G, U} • mRNA: messenger RNA • tRNA: transfer RNA • Other types of RNA: rRNA, miRNA, etc. • Has 5’ and 3’ • Normally single-stranded. But can form secondary structure • Protein: made from 20 kinds of amino acids • Actual worker in the cell • Has N-terminal and C-terminal • Sequence uniquely determined by its gene via the use of codons • Sequence determines structure, structure determines function • Central dogma: DNA transcribes to RNA, RNA translates to Protein • Both steps are regulated

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