Year-end Sale % OFF 
Abstract
In this report, we identify the human DL-methylmalonyl-CoA racemase gene by analyzing prokaryotic gene arrangements and extrapolating the information obtained to human genes by homology searches. Sequence similarity searches were used to identify two groups of homologues that were frequently arranged with prokaryotic methylmalonyl-CoA mutase genes, and that were of unknown function. Both gene groups had homologues in the human genome. Because methylmalonyl-CoA mutases are involved in the metabolism of propionyl-CoA, we inferred that conserved neighbors of methylmalonyl-CoA mutase genes and their human homologues were also involved in this process. Subsequent biochemical studies confirmed this inference by showing that the prokaryotic gene PH0272 and its human homologue both encode DL-methylmalonyl-CoA racemases. To our knowledge this is the first report in which the function of a eukaryotic gene was determined based on the analysis of prokaryotic gene arrangements. Importantly, such analyses are rapid and may be generally applicable for the identification of human genes that lack homologues of known function or that have been misidentified on the basis of sequence similarity searches.
Highlights
Lead to methylmalonyl aciduria, a rare but severe inherited disease [7]
Because methylmalonylCoA mutases are involved in the metabolism of propionyl-CoA, we inferred that conserved neighbors of methylmalonyl-CoA mutase genes and their human homologues were involved in this process
To identify additional genes involved in propionyl-CoA metabolism, we searched for genes that frequently cluster with prokaryotic mcm genes (Fig. 1)
Summary
Lead to methylmalonyl aciduria, a rare but severe inherited disease [7]. Defects in the CblABCDF complementation groups lead to this disease [7]. Knowledge of a gene’s metabolic role can lead to rapid assignment of specific function by focusing biochemical studies Such analyses appear inapplicable to eukaryotes (gene clustering is rare in these organisms), it should be possible to extrapolate the functional information obtained from the analysis of prokaryotic gene arrangements to eukaryotes by homology searches (Fig. 1). To determine whether such analysis can be used to rapidly determine the function of human genes, we investigated genes involved in propionyl-CoA metabolism. Inborn errors in the methylmalonyl-CoA mutase (mcm) gene
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
