30431 Introduktion til Bioinformatik
David Ussery
Fredag, 10 November, 2000

Animated DNA



DNA Symmetry Elements and their Meanings







Overview

This lecture is about ways of looking at DNA sequences in complete genomes and chromosomes, in terms of symmetry elements. There are two parts to this talk. In Part 1, I will discuss the fact that we simply have "Too Much Information" becoming available, and the problem will only get worse in the near future. There are ways of cataloging and organising the data, of course. I have found that the true diversity of genome sizes in Nature is often neglected, so we'll talk for a few minutes about the "C-value paradox", along with some possible ideas for WHY certain organisms have so much DNA.

I would like to think that one way of dealing with the explosion of sequence information, in terms of DNA sequences, is to think about it in biological terms, in particular in physical-chemical terms of structure and function of symmetry elements. For example, there are specific DNA sequences which "code" for a telomere, and different DNA sequences which are specific for centromeres. Specific DNA sequences, their structures, and biological functions will be discussed.

I have also made a separate file, containing specific LEARNING OBJECTIVES for this lecture, as well as a "self-test quiz", which I recommend having a look at, BEFORE the lecture, if possible. I've incorporated the answers to questions 1 and 2 into PART 1 of the lecture notes.


dna53.gif




Part 1 Part 1: The Problem: Too Much Information and Too Many TLA's


Brevis esse laboro,     Obscuro fio.     - Horace


Some philosophical thoughts about Information and the Size of Genomes.

The information in GenBank is doubling every 10 7 months.
What are the implications of this?

growth in GenBank



A look at genome sequencing over the past five years:

YEAR# GENOMES Sequenced
1995
2
1996
4
1997
9
1998
17
1999
30
2000
53


Genome Databases Links





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The "C-value" paradox"

Although the number of genomes being sequenced is increasing rapidly, one has to this into perspective - the genomes of organisms fall very roughly into four different classes:

Organism group Size (bp) No. sequenced
viruses ~1000 bp - 70,000 bp 534
bacteria  ~500,000 - 8,000,000 bp 30
"simple" eukaryotes
~12,000,000 - 270,000,000 bp 2
"complex" eukaryotes
most animals
and some plants
~700,000,000 - ~10,000,000,000 bp
(ave. ~3,000,000,000)
0
"other" eukaryotes 
plants and amoeba
~10,000,000,000 - 670,000,000,000 bp 0

Discussion

Why does amoeba have more than 200x as much DNA as humans?

Think about it for a discussion in class. I have a possible explanation, although I'm not sure anyone really knows the answer to this, to be honest.



This brings us to the first question on the quiz:

Answers to the self-test quiz which you are supposed to do BEFORE the lecture:

1. The short answer - a very long time. About 2.4x1012 years.
     That's about 160 times longer than the estimated age of the universe!



2. The piece of paper would be quite thick - it would reach outside the earth's
     atmosphere and beyond the orbit of the planet Mars.



dna43.gif



Part 2 Part 2: DNA Symmetry Elements and DNA Structures

I will divide "DNA symmetry elements" into 4 different categories.

    Today's lecture will cover:

  1. DNA helical properties

  2. DNA repeat motifs

  3. Next Tuesday's lecture will cover:

  4. DNA mechanical/structural properties

  5. Genomic/chromosomal symmetry elements




Two examples which will be discussed in the lecture



Z-DNA

Regions of alternating purine/pyrimidine steps can form Z-DNA (usually they need to be at least 50% GC rich). These regions are localised in intergenic (non-coding) regions in chromosomes.




A "Z-DNA" Atlas for Leishmania major, chromosome 4

Link to more atlases for Leishmania major chromosomes




DNA repeats

Often DNA repeats can play an important role in homologous recombination. Also, inverted repeats can form stem-loop ("cruciform") structures in bacteria, and play a role in IS elements. For example, the IS elements in the plasmid carrying an enterotoxin gene light up as inverted repeats in the figure below.


A "DNA repeats" Atlas for Escherichia coli, pO157

Link to more atlases


REFERENCES

Papers relevant to this lecture (handed out in class)

    Friday (10 November, 2000)

  1. David W. Ussery, "DNA Structure: A-, B-, and Z-DNA Families", manuscript submitted to The Encyclopedia of Life Sciences, April, 2000.
  2. David W. Ussery and Søren Brunak, "Genome Databases", manuscript submitted to The Encyclopedia of Genetics, October, 2000.
  3. David W. Ussery, "Bioinformatics2000 Meeting Report", Genome Biology, 1, (#3), 1-2, 2000. On-Line Version at http://www.genomebiology.com/2000/1/3/reports/4014/


Other references

  • Richard R. Sinden, Christopher E. Pearson, Vladimir N. Potoman, and David W. Ussery, "DNA: Structure and Function", Advances in Genome Biology, 5A:1-141, (1998).
  • Ussery,D.W., Higgins,C.F., and Bloshoy,A., "Environmental Influences on DNA Curvature", J. Biomolecular Structure & Dynamics,16:811-823, (1999).[PubMed]

  • David W. Ussery, "DNA Denaturation", manuscript submitted to The Encyclopedia of Genetics, September, 2000.
  • Ussery,D.W., Larsen,T.S., Wilkes,K.T., Friis,C., Worning,P., Krogh,A., Brunak,S. "Genome Organisation and Chromatin Structure in Escherichia coli", manuscript submitted to Biochimie, November, 2000.


  • Link to a list of recent papers and talks on DNA structures.



    Books about DNA:

    Sinden,R.R., Pearson,C.E., Potaman,V.N., Ussery,D.W., "DNA: STRUCTURE and FUNCTION", Advances in Genome Biology, 5A:1-141, (1998).

    Calladine,C.R., Drew,H.R., "Understanding DNA: The Molecule and How It Works", (2nd edition, Academic Press, San Diego, 1997).

    A List of more than a thousand books about DNA





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    Last modified Thursday, 9 November, 2000 by David Ussery