Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA...
-
Upload
cathleen-newton -
Category
Documents
-
view
220 -
download
0
Transcript of Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA...
![Page 1: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/1.jpg)
Doug RaifordLesson 7
![Page 2: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/2.jpg)
RNA World Hypothesis RNA world evolved into the
DNA and protein world DNA advantage: greater
chemical stability Protein advantage: more
flexible and efficient enzymes (biomolecules that catalyze)▪ 20 amino acids vs. 4 nucleotides▪ Chemically, more diverse
Remnants remain in ribosomes, nucleases, polymerases, and splicing molecules
![Page 3: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/3.jpg)
Primary: sequence
Secondary: double stranded regions Reverse
complementsTertiary: three-
dimensional structure
>tRNA. Carries amino acid for Isolucine AGGCUUGUAGCUCAGGUGGUUAGAGCGCACCCCUGAUAAGGGUGAGGUCGGUGGUUCAAGUCCACUCAGGCCUACCA
CCA Tail
Acceptor Step
D arm
Anticodon arm
Anticodon
T arm
![Page 4: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/4.jpg)
How find regions of reverse complementation?
What do we have? Sequence A’s like pairing with U’s and
G’s like pairing with C’s Stronger bond (3 hydrogen
bonds) between G’s and C’s Should result in lowest free energy (max
enthalpy)
![Page 5: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/5.jpg)
tRNA Transports amino
acid to the ribosome
CCA Tail
Acceptor Step
D arm
Anticodon arm
Anticodon
T arm
![Page 6: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/6.jpg)
Visualization
![Page 7: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/7.jpg)
Good at finding longer base-pairings (stacked base-pairs)
Need to find the conformation that provides the minimal total free energy
RNA often has many alternate conformations at different temperatures
Stacked base-pairs add stability
Loops/bulges introduce positive free energy and are destabilizing
![Page 8: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/8.jpg)
First nucleotide base-pairs with last
First nucleotide base-pairs with some other (other than last) nucleotide (including none)
Recurse on rest
Recurse on every possible set of two strings
Recurrence relationsRecurrence relations
jkiSESE
SErrSE
jkki
jijiji for )()(min
)(),(min)(
,1,
1,1,
![Page 9: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/9.jpg)
As luck would have it… Zuker came up with a
dynamic programming solution
j
G G G A A A U C C
G 0
G 0
G 0
A 0
A 0
A 0
U 0
C 0
C 0
i
![Page 10: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/10.jpg)
G G G A A A U C C
G 0
G 0 0
G 0 0
A 0 0
A 0 0
A 0 0
U 0 0
C 0 0
C 0 0
Start with zeros on diagonal
Populate diagonally
j
i
![Page 11: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/11.jpg)
Will look at last value to illustrate
Match first and last character, recurse on rest
G G G A A A U C C
G 0 0 0 0 0 0 -1
-2
-3
G 0 0 0 0 0 0 -1
-2
-3
G 0 0 0 0 0 -1
-2
-2
A 0 0 0 0 -1
-1
-1
A 0 0 0 -1
-1
-1
A 0 0 -1
-1
-1
U 0 0 0 0
C 0 0 0
C 0 0
j
i
)2(1
)(),( 1,1
jiji SErr
α A C U G
A 0 0 -1
0
C 0 0 0 -1
U -1
0 0 0
G 0 -1
0 0
![Page 12: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/12.jpg)
G G G A A A U C C
G 0 0 0 0 0 0 -1
-2
G 0 0 0 0 0 -1
-2
-3
G 0 0 0 0 -1
-2
-2
A 0 0 0 -1
-1
-1
A 0 0 -1
-1
-1
A 0 -1
-1
-1
U 0 0 0
C 0 0
C 0
Min of all pairs of substrings
j
i
-3
GGGAAAUCC
GGGAAAUCCG-G-G-A C-C-U
A
A
G-G AC-C-U
A
A
G
![Page 13: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/13.jpg)
n2 plus 2n for each visited cellSo O(n3)
Populate matrix plus traverse
row/column for each cell
![Page 14: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/14.jpg)
Any prediction method must account for these
![Page 15: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/15.jpg)
Now O(n4) Interior loops
most expensive Can exploit the
fact that along diagonals, loops have same size
Can calculate once
Limits search space
Back to O(n3)
kk
kk
kk
LSEkkrr
LSEkrr
LSEkrr
LSErr
Lijrr
LE
LE
jkiSESE
SE
SE
SE
jikjkijik
jikjijik
jijkijik
jijiji
jiji
ji
ji
jkki
ji
ji
ji
size of loopinterior an ofenergy free ingdestabiliz)(
size of bulge a ofenergy free ingdestabiliz)(
pairs baseadjacent ofenergy free gstabilizin
size with loophairpin a ofenergy free ingdestabiliz )(
loopinterior an is if,)()(),(min
jon bulge a is if,)()(),(min
ion bulge a is if,)()(),(min
region helical a is if),(),(
loophairpin a is if),1(),(
)(
)(
for )()(min
)(
)(
min)(
,1,1211
,1,11
,1,11
,1,1
,
,
,
,1,
1,
,1
,
21
![Page 16: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/16.jpg)
Zuker’s site
1 gccgaggtgg tggaattggt agacacgcta ccttgaggtg gtagtgccca atagggctta61 cgggttcaag tcccgtcctc ggtacca
tRNA for Leucine in E. coli, a prototypical organism
Codon: uuaAnti-codon: aat
CCA Tail
Acceptor Step
D arm
Anticodon arm
Anticodon
T arm
![Page 17: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/17.jpg)
Just like proteins: conformation
What if a T-A base-pair mutate to an G-C Still same function
What would this do to a search or sequence alignment?
GCAGGACCAUAUA|||||||||||||CGUCCUGGUAUAU
GCAGGACCAGAUA|||||||||||||CGUCCUGGUCUAU
![Page 18: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/18.jpg)
Phenomenon known as covariance (not to be confused with statistical covariance)
GCAGGACCAUAUA|||||||||||||CGUCCUGGUAUAU
GCAGGACCAGAUA|||||||||||||CGUCCUGGUCUAU
![Page 19: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/19.jpg)
How might we locate covariant pairs?
MSA then compare all pair-wise combinations of columns
High degree of agreement in two columns (G’s match with C’s, A’s match with U’s) an indication of base-pairing
χ2 testCompare to expected number of parings given sequence composition
![Page 20: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/20.jpg)
Pairing depicted with nested parentheses
AAGACUUCGGUCUGGCGACAUUC ((( ))) (( ( )))
![Page 21: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/21.jpg)
Mountain plots
A mountain plot represents a secondary structure in a plot of height versus position, where the height m(k) is given by the number of base pairs enclosing the base at position k. I.e. loops correspond to plateaus (hairpin loops are peaks), helices to slopes.
![Page 22: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/22.jpg)
Circle plot
![Page 23: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/23.jpg)
Data structure capable of capturing secondary structure
Ordered Binary Tree
![Page 24: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/24.jpg)
ProductionsS → aSu | uSa | cSg | gScS → aS | cS | gS | uSS → Sa | Sc | Sg | SuS → SSS →⍉
![Page 25: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/25.jpg)
DerivationS → aSS → aScS → aSccS → acSgccS → acgScgccS → acggSccgccS → acgggScccgccS → acggggSccccgccS → acgggguSccccgccS → acgggguuSccccgccS → acgggguucSccccgccS → acgggguucgSccccgccS → acgggguucgaSccccgccS → acgggguucgaaSccccgccS → acgggguucgaauSccccgccS → acgggguucgaauccccgcc
![Page 26: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/26.jpg)
Parse treea←S | S→c | S→c |c←S→g |g←S→c |g←S→c |g←S→c |g←S→c S→u | |u←S S→a \ / u←S S→a \ / c←S—S→g
![Page 27: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/27.jpg)
Conformation of RNA dictates function Determining secondary structure can
help determine tertiary structure Dynamic programming approach to
identifying minimum energy conformations Zuker MFOLD
View using dot plots, nested parens, mountain or circular plots
Covariance: base-pairs mutate but still form pairs, exploit to find pairings
![Page 28: Doug Raiford Lesson 7. RNA World Hypothesis RNA world evolved into the DNA and protein world DNA advantage: greater chemical stability Protein.](https://reader035.fdocuments.in/reader035/viewer/2022062322/5697bf831a28abf838c8679d/html5/thumbnails/28.jpg)