Evolution of Intron Size in Caenorhabditis elegans

1
Evolution of Intron Size in Caenorhabditis elegans
Mike Palopoli, Anuphap Prachumwat, and Laura
DeVincentis Department of Biology Bowdoin College
2

• What are introns?

The notion of the cistron, the genetic unit of
function that one thought corresponded to a
polypeptide chain, now must be replaced by that
of a transcription unit containing regions which
will be lost from the mature messenger -- which I
suggest we call introns (for intragenic regions)
-- alternating with regions which will be
expressed -- exons. Gilbert, W. (1978) Why
genes in pieces? Nature 271 501
3

• What are introns?

• Stretches of DNA that are transcribed into RNA,
  then spliced out during RNA processing.

• Contain functional elements such as splicing
  signals, regulatory promoters, and other genes.

• Evolve very rapidly in size and content.

• Constitute 26, 11, and 24 of the nematode,
  fly, and human genomes.

What forces drive the evolution of intron size?
4
Relationship between local recombination and
intron size in D. melanogaster (regression on
log-transformed size r -0.026, P 0.001, r2
0.006). Carvalho and Clark (1999).
5

• Evolutionary Model

• Assume that large introns tend to be deleterious.
• Assume that mutation is biased to increase intron
  size.
• Since selection is less effective in regions of
  the genome with reduced recombination, larger
  introns will tend to accumulate in these regions.

6
To test this model further, we measured the
correlation between intron length and
recombination rate in Caenorhabditis elegans.

• Why C. elegans?
• Model organism with sequenced genome.
• Intron size and recombination rate vary greatly
  in the genome of this species.

7
(No Transcript)
8
Recombination Rates Estimated by taking the
first derivative of the polynomial function of
the best-fit curve for genetic distance vs. the
nucleotide coordinate in the genomic sequence
along each chromosome.
9
(No Transcript)
10
Log Intron Size (bp)
Recombination Rate (cM / Mb)
11
Log Intron Size (bp)
Recombination Rate (cM / Mb)
12
Log Intron Size (bp)
Recombination Rate (cM / Mb)
13
(No Transcript)
14
(No Transcript)
15
Opposite correlations between recombination rate
and intron size observed in different
species. To explain regional variation in
intron length across the genome, we propose a new
model based on Chromosome Territories.
16

• Chromosomes adopt predictable, three-dimensional
  positions in the eukaryotic nucleus, termed
  chromosome territories.
• Large-scale structuring of the chromatin is
  thought to play an important role in the
  regulation of gene expression.

17

• Regions between dense pockets of chromatin,
  termed interchromatin compartments, contain high
  concentrations of the macromolecular complexes
  that are essential for transcription and RNA
  processing.
• Regulatory and coding sequences interact most
  effectively with the transcriptional machinery
  when they are positioned at the surface of
  chromatin domains.

18

• Chromosomal regions that contain dense clusters
  of active genes are often located towards the
  center of the nucleus, adjacent to an
  interchromatin compartment, and this arrangement
  can be conserved between divergent species (e.g.,
  Tanabe et al. 2002). This is thought to provide
  the most active genes with the best access to the
  materials needed for transcription and RNA
  processing.

19
Basic Idea Maybe regional variation in intron
size is driven by spatial organization in the
nucleus. If it is beneficial to pack active
genes into the limited spaces adjacent to
interchromatin compartments, then noncoding DNA
would not be allowed to accumulate in those
regions.
20

• Predictions of the CT model
• Intron size variation should be.
• correlated with intergenic space
• - correlated with gene density
• correlated with transposon density
• correlated with pseudogene density
• - correlated with operon density
• - correlated with relative transcript level

21
Average Intergenic Space (bp)
Average Intron Size (bp)
22
Average Gene Density (No. / Mb)
Average Intron Size (bp)
23
Average TE Density (No. / Mb)
Average Intron Size (bp)
24
Average PG Density (No. / Mb)
Average Intron Size (bp)
25
Average Operon Density (No. / Mb)
Average Intron Size (bp)
26
Relative Transcript Level
Average Intron Size (bp)
27
Consistent D. melanogaster Data

• A positive correlation between intergenic space
  and intron size (Hey and Kliman 2002).
• High transposon density near the centromeric
  regions, which is where the majority of large
  introns are located (Adam et al. 2000 Rizzon et
  al. 2002).

28
Acknowledgements

• Biology Dept Bowdoin College
• Patsy Dickinson
• Bruce Kohorn
• Anne McBride
• Educational Technology Center (ETC)