Analysis of gene evolution and metabolic pathways using the Candida Gene Order Browser

Abstract

Background: Candida species are the most common cause of opportunistic fungal infection worldwide. Recent sequencing efforts have provided a wealth of Candida genomic data. We have developed the Candida Gene Order Browser (CGOB), an online tool that aids comparative syntenic analyses of Candida species. CGOB incorporates all available Candida clade genome sequences including two Candida albicans isolates (SC5314 and WO-1) and 8 closely related species (Candida dubliniensis, Candida tropicalis, Candida parapsilosis, Lodderomyces elongisporus, Debaryomyces hansenii, Pichia stipitis, Candida guilliermondii and Candida lusitaniae). Saccharomyces cerevisiae is also included as a reference genome.

Results: CGOB assignments of homology were manually curated based on sequence similarity and synteny. In total CGOB includes 65617 genes arranged into 13625 homology columns. We have also generated improved Candida gene sets by merging/removing partial genes in each genome. Interrogation of CGOB revealed that the majority of tandemly duplicated genes are under strong purifying selection in all Candida species. We identified clusters of adjacent genes involved in the same metabolic pathways (such as catabolism of biotin, galactose and N-acetyl glucosamine) and we showed that some clusters are species or lineage-specific. We also identified one example of intron gain in C. albicans.

Conclusions: Our analysis provides an important resource that is now available for the Candida community. CGOB is available at http://cgob.ucd.ie.

Figure 1

Phylogenetic supertree of Candida species represented in CGOB. Candida glabrata and Saccharomyces cerevisiae have been selected as outgroups. Numbers on branches represent tandem duplications gained along each lineage.

Figure 2

Candida Gene Order Browser (CGOB) screenshot for tandem cluster 32. Each box represents a gene and each color a chromosome (horizontal tracks). The gene in focus is highlighted with an orange border. Gene identifiers in the center of each box relate to annotations from the relevant sequencing centers. The "b" button performs a BLASTP search against CGOB's sequence database. The "S" button displays all the protein sequences in a vertical pillar. The "+" button outputs CGOB pillar data in a tabulated format. The "T" button reconstructs phylogenies on the fly. The "i" button retrieves functional data for C. albicans SC5314 and S. cerevisiae via the Candida Genome Database and the Saccharomyces genome database respectively. Non-syntenic genes are colored in grey. Genes lying in close proximity are joined by connectors: a solid bar for adjacent genes, two narrow bars connect genes up to 5 genes apart (not shown) and one narrow bar connects genes up to 20 genes apart (not shown). Inversions are denoted by orange connectors.

Figure 3

Gene order around tandem clusters 5, 144 and 61 (A, B, C respectively). The diagram is re-drawn from CGOB with some species omitted for clarity. Homologs are organized in pillars. Intron containing genes are indicated with a tail. A) Cluster 5. D. hansenii does not contain an ortholog of FMA1. B) Cluster 144 is represented by a broken red line. GTT1 (orf19.6998) and Cd36_85600 from C. albicans and C. dubliniensis are not part of this cluster, and are located elsewhere in the genome. Diagonal lines indicate a gap of 2 and 4 genes in C. albicans and C. dubliniensis respectively. C) Cluster 61. Diagonal lines indicate a gap of 23 genes in P. stipitis. D) Partial alignment around the C. albicans HGT13 intron. The position of the intron in C. albicans is indicated with an inverted triangle.

Figure 4

Gene order around the biotin cluster. The diagram is re-drawn from CGOB with some genes and species omitted for clarity. Blocks of color represent chromosomes. Homologs are organized in pillars. Changes in color indicate breaks in synteny. The grey triangles indicate an inversion between the C. albicans SC5314 and WO-1 isolates. Diagonal lines indicate local inversions. Genes shown in grey boxes are not adjacent to any other gene shown.

Figure 5

Gene order around the N-acetylglucosamine (NAG) cluster. The diagram is re-drawn from CGOB. Blocks of color represent chromosomes, homologs are organized in pillars and genes shown in grey boxes are not adjacent to any other gene shown. Synteny of NAG enzymes is observed in all species except for C. lusitaniae, which has 5 intervening genes displayed as an insertion loop.

Figure 6

Gene order around the Galactose (GAL) cluster. The diagram is re-drawn from CGOB. Blocks of color represent chromosomes and homologs are organized in pillars. Diagonal lines indicate local inversions. Genes shown in grey boxes are not adjacent to any other gene shown. Dubious genes (orf19.3671 and CLUG_02293) from C. albicans and C. lusitaniae are not displayed.