Selection upon genome architecture: conservation of functional neighborhoods with changing genes

Abstract

An increasing number of evidences show that genes are not distributed randomly across eukaryotic chromosomes, but rather in functional neighborhoods. Nevertheless, the driving force that originated and maintains such neighborhoods is still a matter of controversy. We present the first detailed multispecies cartography of genome regions enriched in genes with related functions and study the evolutionary implications of such clustering. Our results indicate that the chromosomes of higher eukaryotic genomes contain up to 12% of genes arranged in functional neighborhoods, with a high level of gene co-expression, which are consistently distributed in phylogenies. Unexpectedly, neighborhoods with homologous functions are formed by different (non-orthologous) genes in different species. Actually, instead of being conserved, functional neighborhoods present a higher degree of synteny breaks than the genome average. This scenario is compatible with the existence of selective pressures optimizing the coordinated transcription of blocks of functionally related genes. If these neighborhoods were broken by chromosomal rearrangements, selection would favor further rearrangements reconstructing other neighborhoods of similar function. The picture arising from this study is a dynamic genomic landscape with a high level of functional organization.

Figure 1. Distribution of functions present in functional neighborhoods along the phylogeny.

The point at which a function makes up a functional neighborhood has been deduced from the species sharing functional clusters with this particular GO term. Boxes in yellow contain GO terms unique to taxa, boxes in blue contain GO terms common to clades and boxes in pink contain GO terms lost in these lineages. In the figure, terms labeled with P were not found in ape, with G: were not found in chicken, with R were not found in rat and with F were not found in fish.