Coexpression of linked genes in Mammalian genomes is generally disadvantageous.

Similarity in gene expression pattern between closely linked genes is known in several eukaryotes. Two models have been proposed to explain the presence of such coexpression patterns. The adaptive model assumes that coexpression is advantageous and is established by relocation of initially unlinked but coexpressed genes, whereas the neutral model asserts that coexpression is a type of leaky expression due to similar expressional environments of linked genes, but is neither advantageous nor detrimental. However, these models are incompatible with several empirical observations. Here, we propose that coexpression of linked genes is a form of transcriptional interference that is disadvantageous to the organism. We show that even distantly linked genes that are tens of megabases away exhibit significant coexpression in the human genome. However, the linkage is more likely to be broken during evolution between genes of high coexpression than those of low coexpression and the breakage of linkage reduces gene coexpression. These results support our hypothesis that coexpression of linked genes in mammalian genomes is generally disadvantageous, implying that many mammalian genes may never reach their optimal expression pattern due to the interference of their genomic environment and that such transcriptional interference may be a force promoting recurrent relocation of genes in the genome.