Chapter 9

The Cryptococcus Genomes: Tools for Comparative Genomics and Expression Analysis

James W. Kronstad

James W. Kronstad

The Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4

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Brendan J. Loftus

Brendan J. Loftus

Conway Institute, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4 Ireland

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Jennifer K. Lodge

Jennifer K. Lodge

Washington University School of Medicine, Dept. of Molecular Microbiology, St. Louis, MO, 63110

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First published: 12 November 2010

Summary

This chapter describes the genomic resources available for Cryptococcus neoformans and C. gattii and discusses selected examples of the application of the resources to address questions relevant to virulence. It appears that in C. neoformans, natural selection is gradually lengthening short introns and shortening longer introns toward a modal size, which presumably provides an increased level of evolutionary fitness. The current picture, however, may be refined in light of future sequencing of related genomes. Although several studies employed subtractive hybridization methods and differential display to identify genes with specific patterns of regulation, the chapter focuses on experiments with microarrays and serial analysis of gene expression (SAGE) methods. The influence of temperature on gene expression with a shotgun genomic DNA microarray containing 6,274 elements is described in the chapter. The shotgun microarray was used in additional transcriptome profiling experiments to identify targets of Mga2, and these included genes for fatty acid biosynthesis. This study serves to focus attention on fatty acid and sterol metabolism as important aspects of the response to temperature and other stresses. The genome sequences have enabled a series of transcriptome analyses with oligonucleotide microarrays and serial analysis of gene expression. The studies on genome sequences are becoming standard in the analysis of complex traits and the impact of mutations and drug treatments. There is a clear need for a central, curated database for the cryptococcal genome sequences and related resources such as mutant phenotypes, transcriptome and proteome data, protein interaction data, literature, and community information.

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