Functional annotation of Candida albicans hypothetical proteins: a bioinformatics approach.

Candida albicans is a member of the ascomycetes class of fungi and it is an opportunistic pathogen species responsible for a wide range of fungal infections in humans. Bioinformatics and sequencing analysis of Candida proteomics has disclosed that around 69% proteome is still uncharacterized which needs to be annotated with functions. The NCBI-Genome has termed them as hypothetical proteins (HPs) in the whole proteome of Candida. Interpretation of this substantial portion of the proteome can reveal novel pharmacological targets for markers, drug development, and other therapeutics and so on. In this article, we have assigned functional annotation to these hypothetical proteins using bioinformatics methodologies. The advanced and robust computational models have been used to assign the preliminary functions to these putative HPs with high level of confidence. The findings of this study unveil some novel pharmacological targets for drug therapy and vaccines and it would help to identify novel molecular mechanisms underlying the fungal pathogenesis.

Reverse genetic analysis of yeast YPR099C/MRPL51 reveals a critical role of both overlapping ORFs in respiratory growth and MRPL51 in mitochondrial DNA maintenance.

The Saccharomyces cerevisiae genome contains 6572 ORFs, of which 680 ORFs are classified as dubious ORFs. A dubious ORF is a small, noncoding, nonconserved ORF that overlaps with another ORF of the complementary strand. Our study characterizes a dubious/nondubious ORF pair, YPR099C/MRPL51, and shows the transcript and protein level expression of YPR099C. Its subcellular localization was observed in the mitochondria. The overlapping ORF, MRPL51, encodes a mitochondrial ribosomal protein of large subunit. Deletion of any ORF from YPR099C/MRPL51 pair induces common phenotypes, i.e. loss of mtDNA, lack of mitochondrial fusion and lack of respiratory growth, due to the double deletion (ypr099cΔ/Δmrpl51Δ/Δ) caused by sequence overlap. Hence, we created the single deletions of each ORF of the YPR099C/MRPL51 pair by an alternative approach to distinguish their phenotypes and identify the specific functions. Both the ORFs were found essential for the functional mitochondria and respiratory growth, but MRPL51 showed its specific requirement in mtDNA stability. The mechanism of mtDNA maintenance by Mrpl51 is probably Mhr1 dependent that physically interacts with Mrpl51 and also regulates mtDNA repair. Overall, our study provides strong evidence for the protein level expression of a dubious ORF YPR099C and the bifunctional role of Mrpl51 in mtDNA maintenance.