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An Information Flow in Biology Primer
replication (mutation!)
genes
Nucleic acids ~
“software”
DNA
(nucleotides)
transcription
messages
RNA
(nucleotides)
translation
Protein
(amino acids)
~ “hardware”
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/molmast.htm)
• HIV reverse transcriptase (http://www.clunet.edu/BioDev/omm/hivrt/hivrt.htm)
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]
time
species
gene frequency
Chapter VI
Chapter VI
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.
…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.
…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. …
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. …
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
Chapter VI
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.
…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. …
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. …
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.
A phylogeny of Chapter VI’s
Chapter VI
Chapter VI
Chapter VI
Chapter VI
Chapter VI
Chapter VI
Determining Similarity*
* This slide modified from Andreas Matern’s presentation (http://www.people.cornell.edu/pages/alm13/blast/lecture4.html)
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
Example Score
Example
Score
GATACA 2+2+2+2+2+2=12
GATACA
GAAGCC
GATACA
2+2-1-1+2+2=6
GATACC 2+2+2+2+2-1=9
GATACA
GATCCCACA
gap
GAT - - - ACA
2+2+2-1-1-1+2+2+2=9
GAAACA 2+2-1+2+2+2=9
GATACA
GATAC gap
GATACA
2+2+2+2+2-1=9
Situation
for protein
is
more
complex!
This slide taken from Andreas Matern’s 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.
Let’s do a Blast search
Protein
Tyrosine
Kinases
(PTK’s)
Protein
Tyrosine
Phosphatases
(PTP’s)
DPez: 1252 aa, ~ 140kD
FERM
34% identical,
46% similar
to human Pez
WIP
27% identical,
47% similar
to human WIP
PTP
37% identical,
53% similar
to human Pez
FERM
PTP