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Lecture 1



            What is it to be alive?




                                      ©
Lecture 1
Lecture 1
Chapter 1
Lecture 1
Lecture 1
Lecture 1




                     Prokaryotic Gene

 Promoter Protein Coding Sequence            Terminator

     Intron ~20 bp



                     Eukaryotic Gene
             Exon 1                 Exon 2         Exon 3

 Promoter

       Intron ~2kb     Intron>5kb        Intron~5kb
Lecture 1
Lecture 1
So, who’s wrong?




    Both!
Lecture 1



One of the most profound technological
accomplishments in human history is the
  sequencing of the human genome…
Lecture 1


One of the major differences between prokaryotes and
 eukaryotes in the size/complexity of their genomes.
Lecture 1
Lecture 1
Mutation – a change in the nucleotide sequence of the genetic
material of an organism – is the underlying force of evolution.
   •Mistakes during replication
   •Chemical Changes in the nucleic acids
      •UV – dimerization
      •Spontaneous decomposition – base changes
   •Chemical/physical changes at the chromosome level
      •Radiation (X-ray/Gamma) – double-strand breaks
   •Sexual reproduction (polyploidy)
Lecture 1




  More than 200
gene families are
common to all life.
  Most of these
   “orthologous
    genes” are
     essential.
Lecture 1




But how do they do this when
most mutations tend to mess
  things up more than they
       improve them?
They must find a way to
  break free from the
 oppression of natural
      selection
Lecture 1



Duplication events                Retroviruses




                     Horizontal Gene Transfer - genes can be
                     transferred between organisms both in the
                     laboratory, and in nature.
hCYP3A Locus
        Chromosome-7                       ~80% Homology


              40 Kb                           4 Kb 5 Kb
                                P2               P1
   3A43                  3A4           3A7             3A5

   43cDNA               4cDNA         7cDNA           5cDNA

   All have roughly 90% homology in the first 1000 bp of their
                          promoters.
Finta & Zaphiropoulos, 2000                    Gellner et al., 2001
Irreducible complexity
Lecture 1




Eukaryotes often have pseudogenes,
duplicated genes that have accrued
mutations that render them inactive, in
their genomes.
  Mutated regulatory elements, frame
  shifts, addition/loss of stop codons,
  lost splice sites, deleterious mutations,
  etc.
Lecture 1
Conoidea based on 12S Ribosomal RNA
Lecture 1



We make assumptions when we do this…
  •Evolution is real - members of a group share a common
  evolutionary history, and are "closely related," more so to
  members of the same group than to other organisms.
  •Bifurcation - new kinds of organisms may arise when existing
  species or populations divide into exactly two groups.
  •Organisms change over time – closely-related groups are
  share synapomorphies, unique features not present in more
  distant ancestors
And even more when we use gene sequences…
   •Mutations are a “one-way” street
   •We can assign a “value” for every base-pair mutated
   •“horizontal gene transfer” has not occurred among the
   orthologues.
Lecture 1



    The identification and characterization of gene
    orthologues helps us in ever expanding ways:
1. Enhanced discovery
   • By finding regions that are highly conserved, primers can
      be designed to discover orthologues from new species
2. Accelerated science
   • We can compare gene sequences and hint at their
      function, expression patterns, etc.
3. More powerful experiments
   • We can plan methods to genetically engineer just about
      anything
4. GAAATAACA and Pharmacogenomics
   • We can peer into our own genomes and predict certain
      diseases and the success of many treatments

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1 universal features of life on earth

  • 1. Lecture 1 What is it to be alive? ©
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  • 12. Lecture 1 Prokaryotic Gene Promoter Protein Coding Sequence Terminator Intron ~20 bp Eukaryotic Gene Exon 1 Exon 2 Exon 3 Promoter Intron ~2kb Intron>5kb Intron~5kb
  • 16. Lecture 1 One of the most profound technological accomplishments in human history is the sequencing of the human genome…
  • 17. Lecture 1 One of the major differences between prokaryotes and eukaryotes in the size/complexity of their genomes.
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  • 21. Mutation – a change in the nucleotide sequence of the genetic material of an organism – is the underlying force of evolution. •Mistakes during replication •Chemical Changes in the nucleic acids •UV – dimerization •Spontaneous decomposition – base changes •Chemical/physical changes at the chromosome level •Radiation (X-ray/Gamma) – double-strand breaks •Sexual reproduction (polyploidy)
  • 22. Lecture 1 More than 200 gene families are common to all life. Most of these “orthologous genes” are essential.
  • 23. Lecture 1 But how do they do this when most mutations tend to mess things up more than they improve them?
  • 24. They must find a way to break free from the oppression of natural selection
  • 25. Lecture 1 Duplication events Retroviruses Horizontal Gene Transfer - genes can be transferred between organisms both in the laboratory, and in nature.
  • 26. hCYP3A Locus Chromosome-7 ~80% Homology 40 Kb 4 Kb 5 Kb P2 P1 3A43 3A4 3A7 3A5 43cDNA 4cDNA 7cDNA 5cDNA All have roughly 90% homology in the first 1000 bp of their promoters. Finta & Zaphiropoulos, 2000 Gellner et al., 2001
  • 28. Lecture 1 Eukaryotes often have pseudogenes, duplicated genes that have accrued mutations that render them inactive, in their genomes. Mutated regulatory elements, frame shifts, addition/loss of stop codons, lost splice sites, deleterious mutations, etc.
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  • 31. Conoidea based on 12S Ribosomal RNA
  • 32. Lecture 1 We make assumptions when we do this… •Evolution is real - members of a group share a common evolutionary history, and are "closely related," more so to members of the same group than to other organisms. •Bifurcation - new kinds of organisms may arise when existing species or populations divide into exactly two groups. •Organisms change over time – closely-related groups are share synapomorphies, unique features not present in more distant ancestors And even more when we use gene sequences… •Mutations are a “one-way” street •We can assign a “value” for every base-pair mutated •“horizontal gene transfer” has not occurred among the orthologues.
  • 33. Lecture 1 The identification and characterization of gene orthologues helps us in ever expanding ways: 1. Enhanced discovery • By finding regions that are highly conserved, primers can be designed to discover orthologues from new species 2. Accelerated science • We can compare gene sequences and hint at their function, expression patterns, etc. 3. More powerful experiments • We can plan methods to genetically engineer just about anything 4. GAAATAACA and Pharmacogenomics • We can peer into our own genomes and predict certain diseases and the success of many treatments