Evolutionary coupling between the deleteriousness of gene mutations and the amount of non-coding sequences

The phenotypic effects of random mutations depend on both the architecture of the genome and the gene–trait relationships. Both levels thus play a key role in the mutational variability of the phenotype, and hence in the long-term evolutionary success of the lineage. Here, by simulating the evolution of organisms with flexible genomes, we show that the need for an appropriate phenotypic variability induces a relationship between the deleteriousness of gene mutations and the quantity of non-coding sequences maintained in the genome. The more deleterious the gene mutations, the shorter the intergenic sequences. Indeed, in a shorter genome, fewer genes are affected by rearrangements (duplications, deletions, inversions, translocations) at each replication, which compensates for the higher impact of each gene mutation. This spontaneous adjustment of genome structure allows the organisms to retain the same average fitness loss per replication, despite the higher impact of single gene mutations. These results show how evolution can generate unexpected couplings between distinct organization levels.