Project description:The diploid fungal pathogen Candida albicans is a highly heterozygous organism, with numerous non-synonymous substitutions often seen within two alleles. RNA-sequencing of the wild-type strain SC5314 has revealed 233 genes with significant levels of allelic expression imbalance. Overall percentage protein identity comparisons were significantly lower in these differentially expressed alleles. This suggests that two different, perhaps functionally divergent, proteins are being expressed at significantly different quantities by the two alleles of a single gene. Previously, gene expression levels have been correlated with structural factors such as GC content, ORF length and codon usage. Here, these factors were first correlated with overall gene expression data to decipher the relationship they have with gene expression in Candida albicans. These relationships were then used to assess the contribution of these factors to allelic expression imbalance. GC content and codon usage did not differ significantly in differentially expressed alleles whereas ORF length was found to be significantly lower in the allele with lowest expression. This surprising result goes against the overall trend observed between length and gene expression. Differences in GC content and ORF length between alleles correlated strongly with percentage protein identity, suggesting an indirect link between these factors and allelic expression imbalance. One sample (SC5314: wild-type strain) assessed in triplicate and compared to the reference diploid genome
Project description:The diploid fungal pathogen Candida albicans is a highly heterozygous organism, with numerous non-synonymous substitutions often seen within two alleles. RNA-sequencing of the wild-type strain SC5314 has revealed 233 genes with significant levels of allelic expression imbalance. Overall percentage protein identity comparisons were significantly lower in these differentially expressed alleles. This suggests that two different, perhaps functionally divergent, proteins are being expressed at significantly different quantities by the two alleles of a single gene. Previously, gene expression levels have been correlated with structural factors such as GC content, ORF length and codon usage. Here, these factors were first correlated with overall gene expression data to decipher the relationship they have with gene expression in Candida albicans. These relationships were then used to assess the contribution of these factors to allelic expression imbalance. GC content and codon usage did not differ significantly in differentially expressed alleles whereas ORF length was found to be significantly lower in the allele with lowest expression. This surprising result goes against the overall trend observed between length and gene expression. Differences in GC content and ORF length between alleles correlated strongly with percentage protein identity, suggesting an indirect link between these factors and allelic expression imbalance.
Project description:Differential expression between monosoic derivative and parental strain of Candida albicans. The important human pathogen Candida albicans possesses an unusual form of gene regulation, in which the copy number of an entire specific chromosome or a large portion of a specific chromosome changes in response to a specific adverse environment, thus, assuring survival. In the absence of the adverse environment, the altered portion of the genome can be restored to its normal condition. One major question is how C. albicans copes with gene imbalance arising by transitory aneuploid states. Here, we compared transcriptomes from two copies of chromosome 5 (Ch5) in a normal diploid strain 3153A and from a single copy of Ch5 in representative derivative Sor55. Statistical analysis revealed that at least 40% of transcripts from the monosomic Ch5 are fully compensated to a disomic level, thus, indicating the existence of a genome-wide mechanism maintaining cell homeostasis. However, a minor portion of transcripts diminished twofold in accordance with what would be expected for Ch5 monosomy. Another minor portion of transcripts, unexpectedly, increased up to twofold and higher then the disomic level, demonstrating indirect control by monosomy. We suggest that C. albicans unusual regulation of gene expression by the loss and gain of entire chromosomes is coupled with widespread compensation of gene dosage at the transcriptional level.
Project description:Though sequence differences between alleles are often limited to a few polymorphisms, these differences can cause large and widespread allelic variation at the expression level. Such allele-specific expression (ASE) has been extensively explored at the level of transcription but not translation. Here we measured ASE in the diploid yeast Candida albicans at both the transcriptional and translational levels using RNA-seq and ribosome profiling, respectively. Since C. albicans is an obligate diploid, our analysis isolates ASE arising from cis elements in a natural, non-hybrid organism, where allelic effects reflect evolutionary forces. Importantly, we find that ASE arising from translation is of a similar magnitude as transcriptional ASE, both in terms of the number of genes affected and the magnitude of the bias. We further observe coordination between ASE at the levels of transcription and translation for single genes. Specifically, reinforcing relationshipsM-bM-^@M-^Twhere transcription and translation favor the same alleleM-bM-^@M-^Tare more frequent than expected by chance, consistent with selective pressure tuning ASE at multiple regulatory steps. Finally, we parameterize alleles based on a range of properties and find that SNP location and predicted mRNA-structure stability are associated with translational ASE in cis. Since this analysis probes more than 4,000 allelic pairs spanning a broad range of variations, our data provide a genome-wide view into the relative impacts of cis elements that regulate translation. Two biological replicates of WT Candida albicans ribosome profiling and RNA-seq
Project description:This data was generated to compare genome-wide expression differences between a major fungal pathogen of humans, Candida albicans and its less pathogenic relative, Candida dubliniensis, using interspecies hybrids to systematically identify cis-regulatory adaptations.
Project description:The fungal pathogen Candida albicans produces dark-pigmented melanin when grown in a basal medium containing 1 mM l-DOPA as melanin substrate. In the widely used C. albicans strain SC5314, melanin appeared after 3-4 days of incubation in l-DOPA medium. The experiment was designed to reveal cadidate genes associated with melanin biosynthesis by expression profiling at different times of growth with and without L-DOPA added to the medium. Expression profiling of C. albicans revealed very few genes significantly up- or down-regulated by growth in l-DOPA.
Project description:Though sequence differences between alleles are often limited to a few polymorphisms, these differences can cause large and widespread allelic variation at the expression level. Such allele-specific expression (ASE) has been extensively explored at the level of transcription but not translation. Here we measured ASE in the diploid yeast Candida albicans at both the transcriptional and translational levels using RNA-seq and ribosome profiling, respectively. Since C. albicans is an obligate diploid, our analysis isolates ASE arising from cis elements in a natural, non-hybrid organism, where allelic effects reflect evolutionary forces. Importantly, we find that ASE arising from translation is of a similar magnitude as transcriptional ASE, both in terms of the number of genes affected and the magnitude of the bias. We further observe coordination between ASE at the levels of transcription and translation for single genes. Specifically, reinforcing relationships—where transcription and translation favor the same allele—are more frequent than expected by chance, consistent with selective pressure tuning ASE at multiple regulatory steps. Finally, we parameterize alleles based on a range of properties and find that SNP location and predicted mRNA-structure stability are associated with translational ASE in cis. Since this analysis probes more than 4,000 allelic pairs spanning a broad range of variations, our data provide a genome-wide view into the relative impacts of cis elements that regulate translation.
Project description:Transcriptome profiling to identify Cap2/Hap43 regulons in the human fungal pathogen Candida albicans: Wild type vs. cap2D grown in iron-depleted medium