Functional clues for hypothetical proteins based on genomic context analysis in prokaryotes

Doerks, Tobias; Mering, Christian von; Bork, Peer

doi:10.1093/nar/gkh973

Cited by 61 publications

(57 citation statements)

References 34 publications

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“…Even for simple organisms with small genomes, such as prokaryotes, the proportion of genes of unknown function is higher than 35% (Doerks et al, 2004). Some of these uncharacterized proteins are highly conserved among distant organisms, suggesting that they play important roles.…”

Section: Introductionmentioning

confidence: 99%

Functional genomics inDictyostelium: MidA, a new conserved protein, is required for mitochondrial function and development

Torija

Vicente

Rodrigues

et al. 2006

Journal of Cell Science

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Genomic sequencing has revealed a large number of evolutionary conserved genes of unknown function. In the absence of characterized functional domains, the discovery of the role of these genes must rely on experimental approaches. We have selected 30 Dictyostelium discoideum genes of unknown function that showed high similarity to uncharacterized human genes and were absent in the complete proteomes from Saccharomyces cerevisiae and S. pombe. No putative functional motifs were found in their predicted encoded proteins. Eighteen genes were successfully knocked-out and three of them showed obvious phenotypes. A detailed analysis of one of them, midA, is presented in this report. Disruption of midA in Dictyostelium leads to pleiotropic defects. Cell size, growth rate, phagocytosis and macropinocytosis were affected in the mutant. During development, midA- cells showed an enhanced tendency to remain at the slug stage, and spore viability was compromised. The expression of MidA fused to GFP in midA- strain rescued the phenotype and the fused protein was located in the mitochondria. Although cellular oxygen consumption, mitochondrial content and mitochondrial membrane potential were similar to wild type, the amount of ATP was significantly reduced in the mutant suggesting a mitochondrial dysfunction. Metabolomic analysis by natural-abundance 13C-nuclear magnetic resonance has shown the lack of glycogen accumulation during growth. During starvation, mutant cells accumulated higher levels of ammonia, which inhibited normal development. We hypothesize that the lack of MidA reduces mitochondrial ATP synthetic capacity and this has an impact in some but not all energy-dependent cellular processes. This work exemplifies the potential of Dictyostelium as a model system for functional genomic studies.

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Section: Introductionmentioning

confidence: 99%

Functional genomics inDictyostelium: MidA, a new conserved protein, is required for mitochondrial function and development

Torija

Vicente

Rodrigues

et al. 2006

Journal of Cell Science

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“…Majority of proteins has shown approximate similar function on the basis of sequence similarity to proteins with known functions [22][23][24]. Here, in our current study, we Transcription factor A (DTEEC) gene encodes a mitochondrial transcription factor protein which is a prime activator of mitochondrial transcription process as well as it participates in mitochondrial genome replication and repair.…”

Section: Discussionmentioning

confidence: 95%

Identification of Bioactive Peptides in Goat Milk and Their Health Application

Sharma¹,

Rout²,

Kaushik³

et al. 2017

J Adv Dairy Res

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We have identified the bioactive peptides in goat milk using two dimensional gel electrophoresis and mass spectrometry. The milk samples were collected from three healthy breeds of goats at CIRG farms. The milk proteins were isolated using simple centrifugation and were evaluated on the basis of presence of other proteins variants using SDS PAGE and two dimensional gel electrophoresis. The protein profiles of all the milk proteins were same showing the presence of all the major caseins proteins and whey proteins whereas the two dimensional gel electrophoresis resulted gels has shown the presence of various protein spots. These protein spots were analysed under mass spectrometry and found biologically active peptides dipeptidyl peptidase, transcription factor A, Interleukin 12 subunit, oligodendrocyte transcription factor 2. In our study we have reported the biological significance of these peptides identified and their role in human health such as mitochondrial disease, brain malignancies, signaling processes of cytokines and help in generating cytotoxic lymphocyte helps enhance immunity.

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“…The need for both classes would then persist, and hence the theory provides roles for the many proteins that have unknown functions. More than 35% of proteins in prokaryotes 8 and 40% of proteins in eukaryotes 9 have unknown functions. The functional characterization of these proteins has been called "one of the main challenges of modern biology" 9 .…”

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confidence: 99%

A network theory of the origin of life

Gw¹

2016

Preprint

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The origin of life may have been a low probability event that involved both RNA and polypeptides. While such an event would occur with low probability, the probability is not too low in the context of the number of nucleation opportunities on the primitive Earth. The probability for the nucleation event is too small if needed components occur as frequently as disruptive components do, without specific interactions between the two classes. However, if many of the needed components contribute by inhibiting otherwise disruptive components, a high probability for a complex nucleation as the beginning of life event emerges.RNA interference and long non-coding RNAs are ascribed roles in inhibiting components that would otherwise be disruptive in the context of a nucleation event. The theory likewise provides an inhibitory role for the large fraction of proteins (35% to 40%) that have no known function in both prokaryotes and eukaryotes. It is suggested that volcanic ash could provide the large number of random shapes needed as the basis for the nucleation event. Experiments based on that hypothesis are proposed. KeywordsNumber of opportunities, needed components, disruptive components, RNA interference, long non-coding RNA, proteins with unknown function, volcanic ash . CC-BY 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

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Functional clues for hypothetical proteins based on genomic context analysis in prokaryotes

Cited by 61 publications

References 34 publications

Functional genomics inDictyostelium: MidA, a new conserved protein, is required for mitochondrial function and development

Functional genomics inDictyostelium: MidA, a new conserved protein, is required for mitochondrial function and development

Identification of Bioactive Peptides in Goat Milk and Their Health Application

A network theory of the origin of life

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