DNA Properties CSE, Marmara University mimoza.marmara.edu.tr/~m.sakalli/cse546 Oct/19/09

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DNA PropertiesCSE, Marmara University
mimoza.marmara.edu.tr/m.sakalli/cse546Oct/19/0
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• No simple definition of being alive!! (life)..
• Reproducing itself, a default mechanism for every
  alive being
• How about computer programs, crystals, and self
  building and self learning robotics and
  computers..
• Life on earth is a result of an evolutionary
  process, and idea is that all living things have
  a common ancestor and are related through
• Basic components of evolution
• Inheritance
• Variation defined legal moves in genotype space.
• Selection a probabilistic evaluation function
• In Computer Science DNA is a string of symbols
  from alphabet A,C,G,T
• A search through a very large space of possible
  organism characteristics.
• And the words built from the four letter alphabet
  covers all the inherited characteristics (called
  the genotype) of all the organisms.

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The Central Dogma in molecular biology
http//proquestcombo.safaribooksonline.com/0596002
998/blast-CHP-2 3 processes Replication,
Transcription, and Translation. Every cell in our
body has 23 chromosomes in the nucleus and the
genes in these chromosomes are responsible for
almost all of the characteristics (not merely a
physical).
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http//www.ncbi.nlm.nih.gov/books/bv.fcgi?ridmboc
4.figgrp.600, by Bruce Alberts, Alexander
Johnson, Julian Lewis, Martin Raff, Keith
Roberts, and Peter Walter Figure 4-5. The DNA
double helix. (A) A space-filling model of 1.5
turns of the DNA double helix. Each turn of DNA
is made up of 10.4 nucleotide pairs and the
center-to-center distance between adjacent
nucleotide pairs is 3.4 nm. The coiling of the
two strands around each other creates two grooves
in the double helix. As indicated in the figure,
the wider groove is called the major groove, and
the smaller the minor groove. (B) A short section
of the double helix viewed from its side, showing
four base pairs. The nucleotides are linked
together covalently by phosphodiester bonds
through the 3 -hydroxyl (-OH) group of one sugar
and the 5 -phosphate (P) of the next. Thus, each
polynucleotide strand has a chemical polarity
that is, its two ends are chemically different.
The 3 end carries an unlinked -OH group attached
to the 3 position on the sugar ring the 5 end
carries a free phosphate group attached to the 5
position on the sugar ring.
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DNA structure and base pairing

• Polymer of
• Ribose sugar
• Phosphate
• Nitrogenous base
• Bases
• A, C, G, T
• and Uracil
• Pairing rule
• A (R) T (Y)
• G (R) C (Y)
• PuRine, Pyrimidine

Why double-stranded! Chemically and
biophysically more stable!!, allows some error
correction (backup) if accidentally damagedUV
irradiation--.
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(No Transcript)
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RNA - Translation

• Genes (less than 5 of all), providing the coding
  information.
• Instructions for protein synthesis,
• regulatory functions..
• Redundancy translates to robustness!!
• Synonymous codons
• Dual strands
• Diploid
• In translation the information now encoded in RNA
  is deciphered (translated) into instructions for
  making a protein.
• Codon Sets of three nucleotides. Codon
  determines which amino acid to be added next in
  the protein chain.
• For example, GCU, the first codon in the figure,
  codes for alanine.

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The table of the nucleotide triplets (codons) and
their corresponding aa. a uracil (U) is
substituted for a thymine (T). This is Universal
process.. The RNA alphabet is A, C, G, and U,
GAAUUC the third position of a codon is often
insignificant ATG Start codon protein
(methionine) T in the middle hydrophobic aa. 64
possible codons but 20 total aa, start and stop
kind of!!.. Or regulatory functions.
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SNP, single nucleotide polymorphism, wobbling in
the code, neutral synonymous mutations.
Some changes at every third of the DNA sequence,
for example a point mutation such as that shown
below, will not yield any variation of the amino
acid sequence and nor the protein produced, for
example alanine is produced in either case of a U
to a C, therefore a point mutation from U to C
would make no difference.
GCUAGGAUCUCAGGCUCA
Point mutation
GCCAGGAUCUCAGGCUCA
Protein coding sequences are called exons. The
redundant parts are introns, intervening DNA
segments. Both introns and exons are transcribed
into mRNA (see next slide) but only exons remain
in the final transcript. Frameshift of the
sequence 6 possible reading. Therefore it is
important to know which codon to start
translation with, and where to stop.
http//en.wikipedia.org/wiki/Gene
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Splicing of DNA to eliminate introns
A protein-coding region framed with Met (ATG) and
any stop codon is (called an open reading frame).
TAA, TAG, or TGA. An example of an ORF.
.TCGAATGGCATTCGCAGTC..TACTTGCACGCTTGACCGTCATA
AGCA.
In addition, each of the 20 aas have different
chemical properties which cause the protein
chains to form different 3D shapes, and
differentiate their particular functions in the
cell. For example, certain folding patterns
(called tertiary structures) make it possible for
specific enzymes to bind in a particular place.
One change in the DNA sequence could change the
amino acid, which could change the protein
structure. And the enzymes..
A Science Primer http//www.ncbi.nlm.nih.gov/About
/primer/est.html
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Levels and types of genome variations

• Plant genomes may differ from one another in
  different ways
• http//www.igd.cornell.edu/Comparative20Genomics
• Amount of DNA in the nucleus. Quantified in
  picogrms, (also called C-value), varies over
  1000-fold.
• Number and size of chromosomes.
• Differences at the sequence level, both in the
  absolute order of the bases, and in the type
  and number of different classes of sequences.
• Organisms originated millions of years ago, from
  the same sequence should be sharing the same
  sequential structures, family-tree, phylogeny.
• Some of the mechanisms of genetic variations
• Point mutations
• Insertions and deletions
• Translocations
• Transposons, (mobile) jumping genes,
  retrotransposons copying themselves from RNA back
  to DNA reverse transcriptase,
• Splicing, transcription and translation errors

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Finding genes cDNA The genetic sequence could
be analyzed from the DNA, but it has too much
non-genetic junk materials, jut studying mRNA,
however, mRNA and protein are very unstable and
therefore difficult to work with. Instead,
scientists use special enzymes to convert RNA
into complementary DNA (cDNA) which is a much
more stable compound and because it was generated
from a mRNA in which the introns have been
removed, cDNA represents only transcribed DNA
sequence, the genes. Genetic Mapping Used for
linkage mapping, and uses the concepts of
Mendelian inheritance and recombination
frequencies to determine the chromosomal location
by analyzing their inherited patterns. Done by
either Southern blot (electrophoresis separated
fragments subsequently detected by probe
hybridization) and, more recently polymerase
chain reaction - PCR (using thermal cycling)
based methods. A tomato F2 population used to
calculate recombination frequencies, and genetic
distances, between a selection of SSRs simple
sequence repeat (microsatellites) SSRs and other
molecular markers.
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Comparative mapping Among related but sexually
incompatible species, heterologous (between
species) DNA markers can be used to generate
comparative maps and to infer linkage
conservation and the position of orthologous (if
branched from the homologous) loci. This requires
a minimal amount of similarity between the target
and probe species and so cannot be used with more
distantly related species. Most gramineae
genomes (i.e. grass species, maize, rice,
wheat, barley, millet, etc) are connected through
comparative genetic maps. While genome size
varies dramatically among grass species, but the
gene content and gene order remain more highly
conserved..
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Packing of DNA in the nucleus
http//employees.csbsju.edu/hjakubowski/classes/ch
331/DNA/oldnastructure.html
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• Archebacterium living in a superheated sulphur
  vent at the bottom of the ocean
• A two-ton polar bear roaming the arctic circle
• Genome size (length of DNA) varies from 5,000
  (SV40 virus) to 3109 (humans) 1011 (higher
  plants)
• All organism share basic properties
• Made of cells (membrane-enclosed sacks of
  chemicals)
• Carry basic reactions (e.g. core metabolic and
  developmental pathways)

Figure 1-38. Genome sizes compared. Genome size
is measured in nucleotide pairs of DNA per
haploid genome, that is, per single copy of the
genome. (The cells of sexually reproducing
organisms such as ourselves are generally
diploid they contain two copies of the genome,
one inherited from the mother, the other from the
father.) Closely related organisms can vary
widely in the quantity of DNA in their genomes,
even though they contain similar numbers of
functionally distinct genes. (Data from W.-H. Li,
Molecular Evolution, pp. 380 383. Sunderland, MA
Sinauer, 1997.)
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Tree of Life

• Three major groups
• Archaea (recently discovered)
• Bacteria (germs, algae, symbiotic organisms)
• Eukaryotes
• Animals
• Green Plants
• Fungi
• Protists
• Viruses

Figure 1-21. The three major divisions (domains)
of the living world. Note that traditionally the
word bacteria has been used to refer to
procaryotes in general, but more recently has
been redefined to refer to eubacteria
specifically. Where there might be ambiguity, we
use the term eubacteria when the narrow meaning
is intended. The tree is based on comparisons of
the nucleotide sequence of a ribosomal RNA
subunit in the different species. The lengths of
the lines represent the numbers of evolutionary
changes that have occurred in this molecule in
each lineage.