Download Getting Back to Basics

Getting Back to Basics
(Loosely based on Chapter 1, “The Nucleic Acid World,” Zvelebil and Baum, Understanding
Bioinformatics, 2008)
Getting Back to Basics
(Loosely based on Chapter 1, “The Nucleic Acid World,”
Zvelebil and Baum, Understanding Bioinformatics, 2008)
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What are the main purposes of DNA?
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DNA as software
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A common analogy
In what ways is the analogy right?
In what ways is the analogy not right?
Hierarchy of Twists
Source:http://www.personal.psu.edu/drs18/FOLIO/chromatinFiber.jpg
(David R. Strong, multimedia developer)
Hierarchy of Twists
Source:
http://www.cgl.ucsf.edu/Research/chromosome/chromatin/helix/helix.html
Twisting Hierarchies
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If you take a string, rubber band, rope,
wire, etc. and start twisting it, it often
develops a 2nd-level twist after awhile
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If you're careful you can get a 3rd level of
twist
Balsa wood model airplanes do it
You could try it at home
Hierarchy of Twists
Source:
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=hmg&part=A127
Hierarchy of
Twists
Source:
http://www.biochem.arizo
na.edu/classes/bioc462/46
2a/NOTES/Nucleic_Acids/c
hromosome2.jpg
Packing of chromatin in the
chromosome
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The “fractal globule” packing approach
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Bits of DNA close in the linear sequence
are close in the packed 3-D structure
Active genes tend to be near each other
Fractal globule-type structuring enables
easy unpacking for transcription
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Fractal globules are non-knotty
http://www.technologyreview.com/biomedicine/23654/page1/ (summary)
http://www.sciencemag.org/cgi/content/abstract/326/5950/289 (source)
Higher level folding of DNA
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Humans have about 6 feet of DNA
Rolled up in a nucleus
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Nucleus is ≈ 1/10 width of a hair
How they figure out the folding
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“Fix” a DNA molecule in e.g. formaldehyde
Break up the fixed molecule into many pieces
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(Use an enzyme)
Pieces “fixed” together earlier are still stuck together
“Fix” here means _____
What they discovered
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Genes being expressed are near each other
in 1-D and 3-D
The “compartment” of these active genes
is loosely packed
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The compartment of inactive genes is tightly
packed
Stuff nearby in 1-D is nearby in 3-D
There are no knots
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So it is easy to unpack/repack DNA segments
Fractal globules redux
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Picture a package of Ramen noodles!
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(Sort of)
So what happens if you consider genes
in different places in the DNA?
Check pics in
http://www.technologyreview.com/biomedicine/23654/page1/
(summary)
http://www.sciencemag.org/cgi/content/abstract/326/5950/289
(source; see e.g. supplementary materials)
Getting Back to Basics
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The genome is the set of DNA molecules in each
cell of an organism
Humans have only 46 DNA molecules in each cell
They are wrapped and packaged into
chromosomes
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All 46 are different
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“Colored bodies” (chromo- = color, -some = body)
…but can be grouped in pairs of similar members
Sort of like socks…pair #2 is different in chimpanzees
Anyone know the # for some other organism?
DNA Structure
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The variation of the Latin alphabet used in
English has 26 letters
How many types of base does DNA have?
What are their
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Abbreviations?
Names?
Watson-Crick pairings?
DNA Structure (cont.)
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DNA has: A, C, G, & T (A-T, C-G)
Adenine, cytosine, guanine, thymine
Each is part of a nucleotide
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The kind of nucleotides in DNA are
deoxyribonucleotides
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Each combines a base and a deoxyribose
Deoxyribose is a kind of sugar
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(sucrose, glucose, fructose,… are more familiar)
Does deoxyribose taste sweet? What about ribose?
How do deoxyribose and ribose differ?
Some Vocabulary
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Nucleobase: A, C, G, T, & U
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adenine, cytosine, guanine, thymine, uracil
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(also base, nucleotide base, nitrogenous base)
Nucleoside: a nucleobase and
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a ribose or deoxyribose attached
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(deoxy)adenosine, cytidine, guanosine, thymidine, uridine
Nucleotide: a nucleoside phosphate
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Could be mono-/di-/triphosphate
Example: ATP – adenosine triphosphate
DNA Structure (cont.)
Source:
http://ionholdings.co
m/images/dna.jpg
Source:
http://ww
w.scq.ubc.c
a/a-monksflourishinggardenthe-basicsofmolecularbiologyexplained/
DNA Structure (cont.)
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Each nucleotide has a 5’ and a 3’ end
– 3' has a hydroxyl group
• Hydroxyl is attached to carbon #3
– 5' has a phosphate group
• Phosphate is attached to carbon #5
– There are 5 carbon atoms in ribose
DNA Structure (cont.)
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Each nucleotide has a 5’ and a 3’ end
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To string them together:
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connect the 5’ of one to the 3’ of the next
To read the sequence:
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Start with 5’ end of sequence,
then read toward 3’ end
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What do the ‘?’ stand for
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What is the complement of AAG?
DNA Replication
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Break one double strand into two single
strands
Use DNA polymerase to give each base its
complement…
– turning two single strands into two double
strands
DNA Hybridization
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Have two strands, see if they join
If they join, the microarray (or whatever)
is “working”
RNA
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Ribonucleic acid
How is RNA different from DNA?
Trivia fact: you can buy ribose as a dietary
supplement
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It tastes sweet (it’s a sugar)
Should you take it?
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“Now, don't get your shorts in a twist over ribose, Muscle
Monthly is here to clear things up for you.” http://www.mesomorphosis.com/supplement-profiles/ribose.htm
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I have no similar information on
deoxyribose…
RNA, cont.
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Usually single stranded
Thus, strand can fold so parts of it pair
with other parts of itself
This can lead to different shapes
These shapes can have functional
significance
RNA, cont.
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tRNA exemplify shaped, functional
molecules (but are not proteins!)
Claim: RNA can be used to:
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carry genetic information (like DNA)
perform functional duties (like protein)
Thus RNA is proposed as the main
constituent of the first life
The “RNA world” hypothesis
RNA world: molecular evolution
See
http://www.cosmosmagazine.com/node/3325
(Stored locally too)
The “Central Dogma”
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Kind of dumb name, IMO
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In science we want hypotheses & evidence
 We don't want dogma
Fortunately this “dogma” is actually a theory
RNA today has lots of help
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DNA specializes in genetics
Protein specializes in function
RNA specializes in mediating from DNA to protein
The “Central Dogma”
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Actually a well-supported theory that
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Information flows from
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DNA, to
RNA, to
Protein
The DNA-RNA step is called _______
The RNA-protein step is called _______
From DNA to Protein
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From DNA-RNA is one major step
From RNA-protein step is one major step
The codon table focuses on which one?
The name for RNA used for this is ______
Step: From DNA to RNA
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Is a given gene on one DNA strand or two?
Which strand reflects the coded protein
best (careful!):
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the strand with the sequence that physically
leads to the protein, or
the complementary strand that doesn’t?
Which is the “antisense strand”?
Which is the “sense strand”?
Step: From DNA to RNA
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The sense strand is the one that is not
used!
The antisense strand is
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The one that is used to generate mRNA
Also called the anticoding strand
Also called the noncoding strand
Which is most like the RNA
(except for U instead of T):
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The coding strand, or the noncoding strand?
DNA and RNA
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In principle, can genes overlap?
DNA, RNA, Genes
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In principle, can genes overlap?
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Yes, viruses do this. Efficient!
774 pairs of overlapping genes were
known in humans
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(as of textbook published in 2008)
Are the two mRNAs of overlapping
genes different from the two mRNAs of
non-overlapping genes?
From RNA to Proteins
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Triplets map from nucleotides to amino acids
How many triplets are there?
How many amino acids?
Why not use doublets instead of triplets?
Leftover triplets are used for
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Redundancy, Stop codons
Start codon is the same as for methionine
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So why don’t all proteins begin with methionine?
http://www.genome.ou.edu/3653/Lecture7-9_6_06.html
Codon Table: RNA to Proteins
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Let’s look at the standard codon table now
Which amino acids do you know?
Reading Frames
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A given expressed region of a DNA strand
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…has 3 “reading frames”
Two strands – total of 6 reading frames
How to tell which is the right one?
The Right Reading Frame
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Six, so how to tell which is the right one?
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…the one with the fewest stop codons
3 out of the 64 codons are stop codons
So a random sequence of codons
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…codes for how long a sequence of amino acids
(average)?
Most proteins are much longer, so that’s how
to find the right reading frame!
Translation: 3 main kinds of RNA
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mRNA
tRNA
rRNA
Do you remember which is which?
3 main kinds of RNA
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mRNA
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tRNA
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Messenger: goes from DNA into a ribosome
Transfer: carries an amino acid to a ribosome
Each has a 3-base anticodon at one end
Each carries an amino acid at the other
rRNA
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Ribosome: makes proteins per an mRNA
Was the ribosome once an organism?
The joining of amino acids is done by rRNA
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This is consistent with the RNA world hypothesis