Ph.D. course in Biological Sequence Analysis and Protein Modelling

INTRODUCTION - Three Different Views of the Escherichia coli genome.

This includes the following:

1. DNase I Sensitivity - this is scaled such that the black bands represent regions of the DNA that are more likely to be cut by DNase I.

2. Intrinsic Curvature - this is a measure of local curvature of the DNA helix.  The units are such that a larger number is more curved, and a value of "0" reflects DNA that has no curvature at all.  The method used here is based on the "Curvature" programme and calculation scheme of Alexander Bolshoy.

3. Helix Rigidity - this is actually calculated from the propeller twist angles found in crystal structures.  There is a good correlation with propeller twist and helix rigidity.

4.  Helix Deformability - this is based on the analysis of several protein-DNA crystal structuresl; certain dinucleotides had a much greater range of "deformability" than others.   (see Olson et al., 1998).

5. Stacking Energy - this is a thermodynamic parameter, that can be experimentally measured.  The values here are in kcal/mol, and are calculated using the values from Ornstein et al.

6. Position Preference - this measure is from nucleosome positioning data from Andrew Travers.
 
 

note: the first and last measures (in grey in the wheel plot) use tri-nucleotide data, whilst the middle 4 (in colour) use dinucleotide models.
 
 

This includes the following:

1. Individual base contributions - the 4 seperate circles make it possible to spot regions enriched for one particular base (e.g., A near the yagG gene, and G near the phnM gene.  (Maybe I need to work on a better colour scheme - this is still under development, and I'm open to any ideas!)

2. Trinucleotide distribution - this is a measure of the deviation of a particular region from the average for the entire chromosome.  It is also possible to compare the region against a different genome (e.g., cp. Archae vs. Bacteria).
 

3. AT skew and GC skew - this is calculated by the formula (G-C)/(G+C), over a window of 5000 G's (which for E. coli is roughly 10,000 bp).  It should be obvious that in E. coli there's an obvious GC skew, but not an AT skew.  Different organisms have different skews, and although it could in part be explained by codon preference usage, this is probably not the entire explanation.  At any rate, this is a useful measure in distinguishing the replicores in many bacteria.
 
 
 
 

For more E. coli atlases (as well as other genomes), visit the " DNA Structural Atlas of E.coli" web page from our the CBS server!
 
 
 
 
 

So what's this good for?  Who cares?
 

Part 2: What does it all mean?  Is any of this at all useful??

a select gallery of some of my favourite genes (click for link to picture):

rhsA (compare the repeat atlas)
fimB (compare the repeat atlas)
hns
proU
rpoB  (look at gel of E. coli whole-cell protein extract)

some recent findings:

1. Analysis of IS elements in pathogenic E. coli  (e.g., pO157:H7 - repeat atlas, structure atlas, baseatlas)

2. Cluster analysis of E. coli genes

3.  Promoters and intergenic regions are different from coding regions in most bacteria . . .

4. Different promoters have characteristic DNA structural properties

5. Helical periodicities unique to Bacteria vs. Archae
 
 

Part 3: Eukaryotic DNA - DNA Symmetry Elements and DNA Structures

DNA symmetry elements defined

Defined Ordered Sequences (DOS)

 

Direct Repeats

Simple Tandem Repeats

(Longer)Tandem Repeats

Direct (non-tandem)

Phased Repeats

Inverted Repeats

Mirror Repeats

Everted Repeats

 

On the DNA Structural significance of symmetry elements

 

On the Biological "meanings" or usefulness of DNA symmetry elements

Architectural Motifs - e.g. Telomeres - see the DNA Structural Atlas for P. falciparium

 

Gene regulation

Curved DNA - can strongly enhance transcription

Cruciforms

Z-DNA

Triplex-DNA

Parallel-stranded DNA

Recombination

Mutagenesis

Evolution

 

Replication

Apoptosis

link to Cookbook for this afternoon's lecture
 

References

"Three Views of the E. coli Chromosome" will be published in the December 1999 issue of Research in Microbiology, by Lars Juhl Jensen, Carsten Friis, and David Ussery.
 

The results of the E. coli structural atlas are currenly being written in the following manuscript, to be submitted to JMB:
Anders Gorm Pedersen, Lars Juhl Jensen, Hans Henrik Stærfeldt, Søren Brunak and David Ussery, "A DNA Structural Atlas for E. coli and other bacterial genomes"
 

The DNA curvature results presented during the lecture were from the following manuscript:
"Environmental Influences on DNA Curvature", J. Biomolecular Structure & Dynamics, 16:811-823, (1999).
 

"DNA: Structure and Function", by Richard R. Sinden, Christopher E. Pearson, Vladimir N. Potoman, and David W. Ussery, Advances in Genome Biology, 5A, 1-141, (1998).
 
 
 

   For those who might be interested in learning more about DNA, visit my "DNA is like Coke" web page!
 
 

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