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MBE Advance Access published online on January 2, 2008
Molecular Biology and Evolution, doi:10.1093/molbev/msm220
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© The Author 2008. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Article

Complex selection on intron size in Cryptococcus neoformans

Stephanie S. Hughes1, Cedric O. Buckley1 and Daniel E. Neafsey2

Microbial Analysis Group, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142

2 corresponding author: Microbial Analysis Group, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, Email: neafsey{at}broad.mit.edu

Received for publication August 6, 2007. Revision received September 20, 2007. Accepted for publication October 2, 2007.

We conducted a genome-wide analysis of the roles of mutation and selection in sculpting intron size in the fungal pathogen Cryptococcus neoformans. We find that deletion rate is positively associated with intron length and that insertion rate exhibits a weak negative association with intron length. These patterns suggest that long introns as well as extremely short introns in this unusually intron-rich fungal genome are in mutation-selection disequilibrium and that the proportion of constrained functional sequence in introns does not scale linearly with size. We find that UTR introns are longer than coding-region introns, and that first introns are substantially longer than subsequent introns, suggesting heterogeneous distribution of constrained functional sequence and/or selective pressures on intron size within genes. In contrast to Drosophila, we find a positive correlation between dN and first intron or last intron length, and a negative correlation between dN and internal intron length. This contrasting pattern may indicate that terminal introns and internal introns are differentially subject to hypothesized selection pressures modulating intron size, and provides further evidence of widespread selective constraints on noncoding sequences.

Key Words: introns • size • natural selection • Cryptococcus • deletion

1 Present address: Department of Biology, Jackson State University, 1400 J.R. Lynch St., Jackson, MS 39217


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