RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.
-
Upload
colin-hensley -
Category
Documents
-
view
216 -
download
1
Transcript of RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.
![Page 1: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/1.jpg)
RNA & NKS
Erik A. SchultesHedgehog Research
hedgehogresearch.info
June 16, 2006
![Page 2: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/2.jpg)
5’
3’
Ribonucleic Acid:• Universal biopolymer• Linear, polarized
![Page 3: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/3.jpg)
5’
3’
Cytosine
Uracil
Adenine
Guanine
Ribonucleic Acid:• Universal biopolymer• Linear, polarized • 4 distinct nitrogenous bases (nt)• RNA can store genetic info (like DNA)
![Page 4: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/4.jpg)
5’
3’
Cytosine
Uracil
Adenine
Guanine
Ribonucleic Acid:• Universal biopolymer• Linear, polarized • 4 distinct nitrogenous bases• RNA can store genetic info (like DNA)• Base-pairing rules:
A with UC with G
![Page 5: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/5.jpg)
5’
3’
Cytosine
Uracil
Adenine
Guanine
5’
3’
Cytosine
Uracil
Adenine
Guanine
![Page 6: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/6.jpg)
Double-stranded RNA Helix
![Page 7: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/7.jpg)
5’
3’
Cytosine
Uracil
Adenine
Guanine
Ribonucleic Acid:• Universal biopolymer• Linear, polarized • 4 distinct nitrogenous bases• RNA can store genetic info (like DNA)• Base-pairing rules:
A with UC with G
• RNA can act as an enzyme (like proteins)
![Page 8: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/8.jpg)
PrimaryStructure
5 ’ G G A A U U G C G G G AA A G G G G U C A A C A GC C G U U C A G U A C C AA G U C U C A G G G G A AA C U U U G A G A U G G CC U U G C A A A G G G U AU G G U A A U A A G C U GA C G G A C A U G G U C CU A A C C A C G C A G C CA A G U C C U A A G U C AA C A G A U C U U C U G UU G A U A U G G A U G C AGUUCA3’
Single-stranded RNA:
![Page 9: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/9.jpg)
ACGUGGAAUUGCGGGAAGAGGGCAACAGCCGUUCAGUACCAAGUCUCAGGGGAAACUUUGAGAUGGCCUGCAAAGGGUAUUGGUAAUAAGCUGACGUGGUCCUAACCCGCAGUGCCAAGUACGUAGCGCUAUAAGUUAGCUAUAUAGCGCAUUCU5’3’ACA
5 ’ G G A A U U G C G G G AA A G G G G U C A A C A GC C G U U C A G U A C C AA G U C U C A G G G G A AA C U U U G A G A U G G CC U U G C A A A G G G U AU G G U A A U A A G C U GA C G G A C A U G G U C CU A A C C A C G C A G C CA A G U C C U A A G U C AA C A G A U C U U C U G UU G A U A U G G A U G C AGUUCA3’
PrimaryStructure
SecondaryStructure
Single-stranded RNA:
![Page 10: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/10.jpg)
ACGUGGAAUUGCGGGAAGAGGGCAACAGCCGUUCAGUACCAAGUCUCAGGGGAAACUUUGAGAUGGCCUGCAAAGGGUAUUGGUAAUAAGCUGACGUGGUCCUAACCCGCAGUGCCAAGUACGUAGCGCUAUAAGUUAGCUAUAUAGCGCAUUCU5’3’ACA
5 ’ G G A A U U G C G G G AA A G G G G U C A A C A GC C G U U C A G U A C C AA G U C U C A G G G G A AA C U U U G A G A U G G CC U U G C A A A G G G U AU G G U A A U A A G C U GA C G G A C A U G G U C CU A A C C A C G C A G C CA A G U C C U A A G U C AA C A G A U C U U C U G UU G A U A U G G A U G C AGUUCA3’
PrimaryStructure
SecondaryStructure
TertiaryStructure
Single-stranded RNA:
![Page 11: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/11.jpg)
Hammer head
VS
HDV
Group I
Group IIRNAse P
Hairpin
Single-stranded RNA:
![Page 12: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/12.jpg)
16S rRNA
Single-stranded RNA:
![Page 13: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/13.jpg)
16S rRNA Universal Tree of Life
![Page 14: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/14.jpg)
A New Kind of Scienceby Stephen Wolfram
In our everyday experience with computers, the programs that we encounter are normally set up to perform very definite tasks.
![Page 15: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/15.jpg)
In our everyday experience with computers, the programs that we encounter are normally set up to perform very definite tasks.
Key idea:What happens if one instead just looks at simple arbitrarily chosen programs, created without any specific task in mind.
A New Kind of Scienceby Stephen Wolfram
![Page 16: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/16.jpg)
In our everyday experience with computers, the programs that we encounter are normally set up to perform very definite tasks.
Key idea:What happens if one instead just looks at simple arbitrarily chosen programs, created without any specific task in mind.
How do such programs typically behave?
A New Kind of Scienceby Stephen Wolfram
![Page 17: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/17.jpg)
computer (hardware) RNA molecule
program (software) nucleotide sequence
In our everyday experience with computers, the programs that we encounter are normally set up to perform very definite tasks.
Key idea:What happens if one instead just looks at simple arbitrarily chosen programs, created without any specific task in mind.
How do such programs typically behave?
A New Kind of Scienceby Stephen Wolfram
![Page 18: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/18.jpg)
In our everyday experience with RNAs, the sequences that we encounter are normally set up to perform very definite tasks.
Key idea:What happens if one instead just looks at simple arbitrarily chosen sequences, created without any specific task in mind.
How do such sequences typically behave?
/. computer (hardware) RNA molecule
/. program (software) nucleotide sequence
A New Kind of Scienceby Stephen Wolfram
![Page 19: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/19.jpg)
What do we mean by:
RNA & NKS
Arbitrary sequence? RNA behavior?
![Page 20: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/20.jpg)
What do we mean by:
RNA & NKS
generated by random processArbitrary sequence? RNA behavior?
![Page 21: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/21.jpg)
What do we mean by:
RNA & NKS
generated by random processArbitrary sequence? RNA behavior? folding dynamics
![Page 22: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/22.jpg)
Never converges on aunique, specific fold
Rapidly converges on a unique, specific fold
What do we mean by:
RNA & NKS
generated by random processArbitrary sequence? RNA behavior? folding dynamics
![Page 23: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/23.jpg)
Never converges on aunique, specific fold
Rapidly converges on a unique, specific fold
What do we mean by:
RNA & NKS
generated by random processArbitrary sequence? RNA behavior? folding dynamics
HelixPoly(U)
OrderedDisordered
![Page 24: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/24.jpg)
What do we mean by:
RNA & NKS
generated by random processArbitrary sequence? RNA behavior? folding dynamics
Evolved
ComplexNever converges on aunique, specific fold
Rapidly converges on a unique, specific fold
HelixPoly(U)
OrderedDisordered
![Page 25: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/25.jpg)
What do we mean by:
RNA & NKS
generated by random processArbitrary sequence? RNA behavior? folding dynamics
Evolved
Complex Rapidly converges on a unique, specific fold
Helix
Ordered
Never converges on aunique, specific fold
Poly(U)
Disordered
Classes I & IIClass IVClass III
![Page 26: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/26.jpg)
1. Lead II chemical probingsecondary structureuniqueness of folding
2. Native gel electrophoresisuniqueness of foldingsize of fold
3. Analytical centrifugationsize & shape of fold
Analyzing RNA Behavior
RNA & NKS
![Page 27: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/27.jpg)
Control SequencestRNAPHE (76nt)
HDV (85nt)Ligase (87nt)
Reference SequencePoly(U)
Choosing Arbitrary Sequences
RNA & NKS
![Page 28: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/28.jpg)
Control SequencestRNAPHE (76nt)
HDV (85nt)Ligase (87nt)
Reference SequencePoly(U)85
Arbitrary Sequences10 Permuted HDV (85nt)10 Isoheteropolymer (85nt)
Choosing Arbitrary Sequences
RNA & NKS
![Page 29: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/29.jpg)
Automated DNA Synthesis
![Page 30: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/30.jpg)
OHOOBasePOOOOHOOBaseCH2CH2
Structure Probing with Pb++
Pb++
![Page 31: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/31.jpg)
OHOOBasePOOOOHOOBaseCH2CH2
Pb++
Structure Probing with Pb++
![Page 32: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/32.jpg)
OHOOBasePOOOHOOBaseCH2CH2OH
Pb++
Structure Probing with Pb++
![Page 33: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/33.jpg)
CGGGCGGGCGGCGUCGCGUCCGACGUCCGUACGUCCGCGUACGUCCGACGUACGUCACGACGUACGUACGACGACGUUAGCGCGC5’3’
OH ladderT1 ladderTimeOHOOBasePOOOHOOBaseCH2CH2OH
HDV
Structure Probing with Pb++
![Page 34: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/34.jpg)
CGGGCGGGCGGCGUCGCGUCCGACGUCCGUACGUCCGCGUACGUCCGACGUACGUCACGACGUACGUACGACGACGUUAGCGCGC5’3’
OH ladderT1 ladderTimeOHOOBasePOOOHOOBaseCH2CH2OH
HDV
Structure Probing with Pb++
![Page 35: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/35.jpg)
Arbitrary sequences acquire sequence-specific folds
![Page 36: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/36.jpg)
8% (29:1)100mM THE, pH7.530mM KCl 0, 1, 10mM MgCl2
3W, 2000VhrXC = 100mmT = 23-24 ºC
Native Gel Electrophoresis
-
+
![Page 37: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/37.jpg)
Arbitrary sequences acquire compact folds
![Page 38: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/38.jpg)
Inferring molecular size and shape from the concentration distribution of puresample under a centrifugal filed.
Sedimentation Velocity Experiments
![Page 39: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/39.jpg)
Reference
Sample
Sedimentation Velocity Experiments
![Page 40: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/40.jpg)
Meniscus
Sedimentation Velocity Experiments
RNA
![Page 41: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/41.jpg)
A260
r (cm)
Fs
Sedimentation Velocity Experiments40,000 RPM100,000 Xg
![Page 42: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/42.jpg)
tRNA
Sedimentation Velocity Experiments
A260
r (cm)
S=4.072 SD=8.45 FicksM=25.2 kDaRs=26.2 Å
![Page 43: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/43.jpg)
Arbitrary sequences acquire compact folds
![Page 44: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/44.jpg)
The behavior of arbitrary RNA
Arbitrary sequences frequently have compact, sequence specific folding - properties that have always been assumed to be evolutionarily derived.
So far:20 seq, 2 compositions = (1/2 postdoc)
![Page 45: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/45.jpg)
The behavior of arbitrary RNA
Arbitrary sequences frequently have compact, sequence specific folding - properties that have always been assumed to be evolutionarily derived.
So far:20 seq, 2 compositions = (1/2 postdoc)
Next step:35,000 seq, 1700 compositions = ($100M)
![Page 46: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/46.jpg)
The behavior of arbitrary RNA
Arbitrary sequences frequently have compact, sequence specific folding - properties that have always been assumed to be evolutionarily derived.
Principle of Computational Equivalenceweak RNA PCE: complex, biologically relevant folds are abundant in seq space
![Page 47: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/47.jpg)
The behavior of arbitrary RNA
Arbitrary sequences frequently have compact, sequence specific folding - properties that have always been assumed to be evolutionarily derived.
Principle of Computational Equivalenceweak RNA PCE: complex, biologically relevant folds are abundant in seq spacestrong RNA PCE: specific folds may beabundant in seq space
![Page 48: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/48.jpg)
Distribution of Folds inRNA Sequence Space
![Page 49: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/49.jpg)
3'AGGGGUCGGUCCACCUCCGCGGUCCGACUCGGGCAUCGAUGG CUAAGGACGAAUGC GGCGAUUAGGGGUUUUCCUAGGUACCUCUCGGC3'GGCAACUCGUCUAAACGCCGGGUGAAGAUGCCCpppCAGUCGGUGGAUGUUAGGGGCGGACCACGUUUUUUUUC U ACCA 2' HOGU CAAACGClass IIIligaseHDV
Prototype Ribozymes
![Page 50: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/50.jpg)
AUUAAAAGCCGCUGGGCCGCCUCCUCGCGGCCGGCCCCGAUAAGGGAGGAAUUUUUCCACGGGACUCCGGAGUGUGGGCUGACHDV fold A GUA C3’U UGAACCCCUCUGGGGGCCCGCCUAACACGACGUCGUGCCGGAAACUppp2' HOCAGUCGGUGGGAGCUGCCGGAGGGAAGGAUG3’UCUUU AACCLigase foldCC
Intersection Sequence
![Page 51: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/51.jpg)
Testing for Ligation & Cleavage
![Page 52: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/52.jpg)
Connecting the Prototypesby Neutral Paths
![Page 53: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/53.jpg)
Connecting the Prototypesby Neutral Paths
Prototype Ligase
42 mutations
![Page 54: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/54.jpg)
Connecting the Prototypesby Neutral Paths
Prototype HDV
Prototype Ligase
42 mutations
44 mutations
![Page 55: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/55.jpg)
Intersection of Fitness Landscapes
![Page 56: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/56.jpg)
1. RNA NN exist - seq space is highly redundant in folds
1. New folds from existing folds
2. RNAs with different sequences and folds could still share ancestry
2. Different NN are proximal
Conclusion
Biological Implications
![Page 57: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/57.jpg)
NKS and Neutral Networks
1. Are INT sequences typical or rare?
2. Are sequences on NN typical or evolved?
![Page 58: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/58.jpg)
NKS and Neutral Networks
1. Are INT sequences typical or rare?
2. Are sequences on NN typical or evolved?
3. Does CA rule space have NN?4. If so, are there INT rules?
![Page 59: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/59.jpg)
Acknowledgments
David P. BartelWhitehead Institute
NSF/Alfred P. Sloan FellowshipTMF/Charles A. King Trust Fellowship
![Page 60: RNA & NKS Erik A. Schultes Hedgehog Research hedgehogresearch.info June 16, 2006.](https://reader030.fdocuments.us/reader030/viewer/2022013003/5514708c550346414e8b6067/html5/thumbnails/60.jpg)