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CRISPR-mediated Genome Editing of the Human Fungal Pathogen Candida albicans
Published on: November 14, 2018
Computational and experimental approaches double the number of known introns in the pathogenic yeast Candida albicans
Quinn M Mitrovich1, Brian B Tuch, Christine Guthrie
1Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143-2200, USA. quinn.mitrovich@ucsf.edu
Abstract:
Candida albicans is the most common fungal pathogen of humans. Frequently found as a commensal within the digestive tracts of healthy individuals, C. albicans is an opportunistic pathogen that causes a wide variety of clinical syndromes in immuno-compromised individuals. A comprehensive annotation of the C. albicans genome sequence was recently published. Because many C. albicans coding sequences are interrupted by introns, proper intron annotation is essential for the accurate definition of genes in this pathogen. Intron annotation is also important for identifying potential targets of splicing regulation, a common mechanism of gene control in eukaryotes. In this study, we report an improved annotation of C. albicans introns. In addition to correcting the existing intron annotations, 25% of which were incorrect, we have used novel computational and experimental approaches to identify new introns, bringing the total to 415, almost double the number previously known. Our identification methods focus primarily on intron features rather than protein-coding features, overcoming biases of traditional intron annotation methods. Introns are not randomly distributed in C. albicans, and are over-represented in genes involved in specific cellular processes, such as splicing, translation, and mitochondrial respiration. This nonrandom distribution suggests functional roles for these introns, and we demonstrate that splicing of two transcripts whose introns have unusual sequence features is responsive to environmental factors.
Insights
Improved annotation of Candida albicans introns reveals nearly double the known number. These fungal pathogen introns are crucial for gene definition and show non-random distribution, suggesting functional roles.
Area of Science:
- Mycology
- Genomics
- Molecular Biology
Background:
- Candida albicans is a common human fungal pathogen and opportunistic pathogen.
- Accurate intron annotation is crucial for defining genes and understanding gene regulation in C. albicans.
- Existing intron annotations in C. albicans were found to be significantly inaccurate.
Purpose of the Study:
- To improve the annotation of introns in the Candida albicans genome.
- To identify novel introns using computational and experimental approaches.
- To investigate the distribution and potential functions of C. albicans introns.
Main Methods:
- Developed novel computational and experimental methods for intron identification.
- Focused on intron features rather than protein-coding features to overcome annotation biases.
- Analyzed the distribution of introns across C. albicans genes and pathways.
Main Results:
- Successfully corrected existing intron annotations, with 25% found to be inaccurate.
- Identified 415 introns in C. albicans, nearly doubling the previously known number.
- Discovered that introns are over-represented in genes related to splicing, translation, and mitochondrial respiration.
- Demonstrated that splicing of certain transcripts with unusual introns is environmentally responsive.
Conclusions:
- The improved intron annotation provides a more accurate genomic framework for C. albicans research.
- The non-random distribution and environmental responsiveness suggest functional significance for C. albicans introns.
- This work enhances our understanding of gene regulation and pathogenicity in this important fungal pathogen.
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