Regional Variation in the Density of Essential Genes in Mice

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Abstract
In most species, and particularly in vertebrates, the percentage of genes absolutely required for survival, the essential genes, has not been estimated. To obtain this estimation, we used the mouse as an experimental model to carry out high-efficiency N-ethyl-N-nitrosourea (ENU) mutagenesis screens in two balancer chromosome regions, and compared our results to a third previously published screen. The number of essential genes in each region was predicted based on allele frequencies. We determined that the density of essential genes differs by up to an order of magnitude among genomic regions. This indicates that extrapolating from regional estimates to genome-wide estimates of essential genes has a huge variance. A particularly high density of essential genes on mouse Chromosome 11 coincides with a high degree of regional linkage conservation, providing a possible causal explanation for the density variation. This is the first demonstration of regional variation in essential gene density in the mouse genome. The genome sequences of many organisms are now complete. However, speculation remains regarding the function of many newly discovered genes. There is also debate about the percentage of genes that are required to build an organism. These genes, which are necessary for the development of the organism, are essential genes. We have performed mutagenesis screens that allow the identification of mutations in essential genes from specific regions of the mouse genome. From these data we have predicted the number of essential genes in three regions of the mouse genome. When we compared these predictions, we found that the density of essential genes varies in different regions of the mouse genome. We then analyzed these regions of the genome to identify similar regions in other mammals. We found that regions of the mouse genome with a high density of essential genes are more similar to other species than those regions with fewer essential genes, suggesting that throughout evolution genomic regions with many essential genes remain intact.