Patterns of Evolutionary Conservation of Essential Genes Correlate with Their Compensability

Abstract

Essential genes code for fundamental cellular functions required for the viability of an organism. For this reason, essential genes are often highly conserved across organisms. However, this is not always the case: orthologues of genes that are essential in one organism are sometimes not essential in other organisms or are absent from their genomes. This suggests that, in the course of evolution, essential genes can be rendered nonessential. How can a gene become non-essential? Here we used genetic manipulation to deplete the products of 26 different essential genes in Escherichia coli. This depletion results in a lethal phenotype, which could often be rescued by the overexpression of a non-homologous, non-essential gene, most likely through replacement of the essential function. We also show that, in a smaller number of cases, the essential genes can be fully deleted from the genome, suggesting that complete functional replacement is possible. Finally, we show that essential genes whose function can be replaced in the laboratory are more likely to be non-essential or not present in other taxa. These results are consistent with the notion that patterns of evolutionary conservation of essential genes are influenced by their compensability—that is, by how easily they can be functionally replaced, for example through increased expression of other genes.

Author Summary

In any given organism, a fraction of all genes in the genome are required for viability; if they are experimentally deleted, the organism dies. Interestingly, the set of essential genes is usually not identical even for closely related organisms. Genes that are essential in one organism are sometimes nonessential in sister taxa or even missing from their genomes. This suggests that, in the course of evolution, some genes can be rendered non-essential and consequently can be lost. How can genes become non-essential? It is possible that changes in an organism's living conditions render previously essential functions unessential. Alternatively, it is possible that, during evolution, the function of an essential gene can be taken over by another gene, so that the essential gene becomes dispensable. Here, we tested the second hypothesis experimentally in the laboratory. We tried to replace the functions of essential genes in the bacterium Escherichia coli. We find that the genes that can easily be replaced in the laboratory are also more likely to be lost in the course of evolution. This suggests that differences in the evolutionary fate between essential genes can be partially explained by how easily their functions can be taken over by other genes.