Genomic Identification And Functional Analysis Of Essential Genes In Caenorhabditis Elegans

Background: Essential genes are required for an organism's viability,and the ability to identify these genes in pathogens is crucial to directed drug development.The functions of essential genes vary greatly and spread across many pathways.Due to the importance of essential genes,large scale efforts have been undertaken to identify the complete set of essential genes and to understand their function.In C.elegans,RNAi knock-down phenotypes were examined for roughly 92% of the C.elegans genes,while it is limited to only knock-down gene expression instead of fully knock-out gene expression.An effectively way to screen and maintain lethal mutations is to use genetic balancer systems.Studying genome architecture and organization found that genes are not randomly disturbed in the genome.Results: Using combined genetic mapping,Illumina sequencing,and bioinformatics analyses approaches,we successfully identified 104 essential genes with 265 lethal mutations in genomic regions of C.elegans of around 22.5 Mb from Chromosome ?(left),Chromosome ?(mid)and Chromosome ?(left).Examine essential genes with Hi-C data shows that essential genes tend to cluster within topologically associating domains units rather near topologically associating domain boundaries.We have shown that essential genes in the left half of chromosome ? in C.elegans function in enzyme and nucleic acid binding activities during fundamental processes,such as DNA replication,transcription,and translation.Furthermore,we found that essential genes exhibit more protein connectivity than non-essential genes in the genome,suggests that essential genes tend to engage in protein interaction hubs.Also,many of the essential genes show strong expression in embryos or early larvae stages,indicating that they are important to early development.Conclusions: We comprehensively analyzing genomic mutations in 265 mutants of C.elegans and successfully identified 104 essential genes with high confidence.Highthroughput sequencing of balanced lethal mutations has proved that it is more efficient and cost-effective than the traditional method,which undertakes dozens of Sanger sequencing of genes in a particular genetic mapping zone.Our result confirmed that this work provided a more comprehensive picture of the essential gene and their functional characterization.These genetic resources will provide as important tools for further health and disease research.