AI Article Synopsis
- Combined genetic mapping and sequencing identified 60 essential genes linked to 104 lethal mutations across two regions of chromosomes III and V, with some genes previously unassociated with lethality.
- Analysis revealed four potential new protein domains and showed that most essential genes encode for enzymes, particularly involved in nucleic acid binding and fundamental cellular processes like DNA replication and translation.
- The study highlights that essential genes exhibit traits similar to human disease genes, with a significant overlap (90%) in human orthologs, emphasizing their relevance for understanding human diseases.
Article Abstract
Using combined genetic mapping, Illumina sequencing, bioinformatics analyses, and experimental validation, we identified 60 essential genes from 104 lethal mutations in two genomic regions of totaling ∼14 Mb on chromosome III(mid) and chromosome V(left). Five of the 60 genes had not previously been shown to have lethal phenotypes by RNA interference depletion. By analyzing the regions around the lethal missense mutations, we identified four putative new protein functional domains. Furthermore, functional characterization of the identified essential genes shows that most are enzymes, including helicases, tRNA synthetases, and kinases in addition to ribosomal proteins. Gene Ontology analysis indicated that essential genes often encode for enzymes that conduct nucleic acid binding activities during fundamental processes, such as intracellular DNA replication, transcription, and translation. Analysis of essential gene shows that they have fewer paralogs, encode proteins that are in protein interaction hubs, and are highly expressed relative to nonessential genes. All these essential gene traits in are consistent with those of human disease genes. Most human orthologs (90%) of the essential genes in this study are related to human diseases. Therefore, functional characterization of essential genes underlines their importance as proxies for understanding the biological functions of human disease genes.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844317 | PMC |
| http://dx.doi.org/10.1534/g3.117.300338 | DOI Listing |
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