DNA

1
An Information Flow in Biology Primer
replication (mutation!)
genes
DNA
Nucleic acids software
(nucleotides)
transcription
messages
RNA
(nucleotides)
translation
Protein
(amino acids)
hardware
2
Examples of DNA and Protein Structure

• DNA
• http//www.clunet.edu/BioDev/omm/dna.htm
• Protein
• amino acids (http//www.clunet.edu/BioDev/omm/aa/
  aa.htm)
• antibody (http//www.clunet.edu/BioDev/omm/ig/mol
  mast.htm)
• HIV reverse transcriptase (http//www.clunet.edu/
  BioDev/omm/hivrt/hivrt.htm)

3
An Evolution by Natural Selection Primer

• Mutations (hence new varieties) do not arise
  because they are needed -- they arise by chance
• Mutations merely furnish random raw material for
  evolution, and rarely, if ever determine the
  course of the process
• Natural selection is the differential
  reproduction of genotypes (genes)
• Evolution is the change in the genetic
  composition of a population over time Natural
  Selection is not Evolution Ronald Fisher, The
  Genetical Theory of Natural Selection
• see the Weasel applet for a demonstration of the
  power of selection

4
species
gene frequency
time
5
Chapter VI Organs of extreme perfection and
complication. -- To suppose that the eye, with
all its inimitable contrivances for adjusting the
focus to different distances, for admitting
different amounts of light, and for the
correction of spherical and chromatic aberration,
could have been formed by natural selection,
seems, I freely confess, absurd in the highest
possible degree. Yet reason tells me, that if
numerous gradations from a perfect and complex
eye to one very imperfect and simple, each grade
being useful to its possessor, can be shown to
exist if further, the eye does vary ever so
slightly, and the variations be inherited, which
is certainly the case and if any variation or
modification in the organ be ever useful to an
animal under changing conditions of life, then
the difficulty of believing that a perfect and
complex eye could be formed by natural selection,
though insuperable by our imagination, can hardly
be considered real.
Chapter VI Organs of extreme perfection and
complication. -- To suppose that the eye, with
all its inimitable contrivances for adjusting the
focus to different distances, for admitting
different amounts of light, and for the
correction of spherical and chromatic aberration,
could have been formed by natural selection,
seems, I freely confess, abserd in the highest
possible degree. Yet reason tells me, that if
numerous gradations from a perfect and complex
eye to one very imperfect and simple, each grade
being useful to its possessor, can be shown to
exist if further, the eye does vary ever so
slightly, and the variations be inherited, which
is certainly the case and if any variation or
modification in the organ be ever useful to an
animal under changing conditions of life, then
the difficulty of believing that a perfect and
complex eye could be formed by natural selection,
though insuperible by our imagination, can hardly
be considered real.
Chapter VI Organs of extreme perfection and
complication. -- To suppose that the eye, with
all its inimitable contrivances for adjusting the
focus to different distances, for admitting
different amounts of light, and for the
correction of spherical and chromatic aberration,
could have been formed by natural selection,
seems, I freely confess, abserd in the highest
possible degree. Yet reason tells me, that if
numerous gradations from a perfect and complex
eye to one very imperfect and simple, each grade
being useful to its possesser, can be shown to
exist if further, the eye does vary ever so
slightly, and the variations be inherited, which
is certainly the case and if any variation or
modification in the organ be ever useful to an
animal under changing conditions of life, then
the difficulty of believing that a perfect and
complex eye could be formed by natural selection,
though insuperible by our imagination, can hardly
be considered real.
Chapter VI Organs of extreme perfection and
complication. -- To suppose that the eye, with
all its inimitable contrivances for adjusting the
focus to different distances, for admitting
different amounts of light, and for the
correction of spherical and chromatic aberration,
could have been formed by natural selection,
seems, I freely confess, abserd in the highest
possible degree. Yet reason tells me, that if
numerous gradations from a perfect and complex
eye to one very imperfect and simple, each grade
being useful to its possessor, can be shown to
exist if further, the eye does vary ever so
slightly, and the variations be inherited, which
is certainly the case and if any variation or
modification in the organ be ever useful to an
animal under changing conditions of life, then
the difficulty of believing that a perfect and
complex eye could be formed by natural selection,
though insuperable by our imagination, can hardly
be considered real.
Chapter VI Organs of extreme perfection and
complication. -- To suppose that the eye, with
all its inimitable contrivances for adjusting the
focus to different distances, for admitting
different amounts of light, and for the
correction of spherical and chromatic aberration,
could have been formed by natural selection,
seems, I freely confess, abserd in the highest
possible degree. Yet reason tells me, that if
numerous gradations from a perfect and complex
eye to one very imperfect and simple, each grade
being useful to its possessor, can be shown to
exist if further, the eye does vary ever so
slightly, and the variations be inherited, which
is certainly the case and if any variation or
modification in the organ be ever useful to an
animal under changing conditions of life, then
the difficulty of believing that a perfect and
complex eye could be formed by natural selection,
though insuperible by our imagination, can hardly
be considered real.
Chapter VI Yet reason tells me, that if numerous
gradations from a perfect and complex eye to one
very imperfect and simple, each grade being
useful to its possesser, can be shown to exist
if further, the eye does vary ever so slightly,
and the variations be inherited, which is
certainly the case and if any variation or
modification in the organ be ever useful to an
animal under changing conditions of life, then
the difficulty of believing that a perfect and
complex eye could be formed by natural selection,
though insuperible by our imagination, can hardly
be considered real. Organs of extreme
perfection and complication. -- To suppose that
the eye, with all its inimitable contrivances for
adjusting the focus to different distances, for
admitting different amounts of light, and for the
correction of spherical and chromatic aberration,
could have been formed by natural selection,
seems, I freely confess, abserd in the highest
possible degree.
6
A phylogeny of Chapter VIs
Chapter VI
Chapter VI
Chapter VI
Chapter VI
Chapter VI
Chapter VI
7
Determining Similarity To determine how
similar your sequence is to other sequences in
the database, you rely on scores determined by
the program you are using. The scores are
generated in different ways for each of the
different programs, but, in general scores are
determined by substitution matricies. To
understand how these matricies work, let's look
at he simplest case aligning two nucleotide
sequences. Generally, when two nucleotide
sequences are aligned, the scores are as
follows 2 identity -1 mismatch
This slide modified from Andreas Materns
presentation (http//www.people.cornell.edu/pages/
alm13/blast/lecture4.html)
Example Score GAAGCC 22-1-1226 GATACA

GATCCCACA 222-1-1-12229 gap GAT
- - - ACA
GATAC - 22222-19 gap
GATACA
Example Score GATACA 22222212 GATACA
GATACC 22222-19 GATACA
GAAACA 22-12229 GATACA
Situation for protein is more complex!
8
This slide taken from Andreas Materns
presentation (http//www.people.cornell.edu/pages/
alm13/blast/lecture6.html)
BLAST - Basic Local Alignment Search Tool J.
Mol. Biol. (1990) 215 403-410. Altschul SF, Gish
W, Miller W, Myers EW, Lipman DJ BLAST sifts
through the huge amounts of data in a database,
scanning a nucleotide database at 2 x 106 bases
per second, and a protein database at 500,000
residues a second! How does it do it so
fast? Well, this is a little hairy -- and
probably more statistics than anyone really needs
to know. I'll try to add some of the statistical
stuff at a later date, but for now remember that,
as previously mentioned, BLAST does not go
through each an every sequence, it uses a LOCAL
alignment heuristic. Without belaboring the
statistics, BLAST divides your sequence into
words - smaller segments with a given length (w).
Nucleotides are normally broken up into words of
length w 12. Then, BLAST goes through the
database (which has also been broken up into
words) to find pairs with a score above a
predetermined threshold. However, using a
statistical heuristic which Karlin and Altschul
developed, BLAST can eliminate some of these
attempted word pairings by estimating a score at
which a match is no better than chance. By
ignoring all searches at and below this score,
BLAST can effectively disregard a great deal of
the database. BLAST finds only those pairs that
contain a score of at least T - a threshold
value. Once it finds a hit, it then tries to
extend that hit until a cutoff score (S) is
reached. Extending means that it adds letters to
the ends of the word pair and then assesses the
new score. To reiterate 1.Cut up the
sequences into smaller pieces called words
2.Ignore all pairs below the threshold score
3.Try to extend all remaining hits until you get
to a cutoff score In the original BLAST paper,
Altschul et al go through a series of tests to
generate (via random simulation and through real
data) values of w, T, and S which are the most
biologically relevant and yet computationally
useful. Generally speaking, the lower the
threshold (T) value is, the greater the chance of
finding a "hit" of at least S. However, small
values of T increase the number of hits, and
therfore the amount of time it takes for BLAST to
sort through the database.
9
Lets do a Blast search
10
(No Transcript)
11
Protein Tyrosine Kinases (PTKs)
Protein Tyrosine Phosphatases (PTPs)
12
DPez 1252 aa, 140kD
WIP
PTP
FERM
27 identical, 47 similar to human WIP
34 identical, 46 similar to human Pez
37 identical, 53 similar to human Pez
13
FERM
PTP