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.

This work is supported by grants BIO2008-04212, BFU2009-13409-C02-02, and BFU2006-15413-C02-01 from the Spanish Ministry of Science and Innovation, and PROMETEO/2010/001 from the GVA-FEDER. The National Institute of Bioinformatics (www.inab.org) and The CIBER de Enfermedades Raras are initiatives of the ISCIII. This work is also partially supported by a grant (RD06/0020/1019) from Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Instituto de Salud Carlos III (ISCIII), and the Spanish Ministry of Science and Innovation. The funders had no role in study design, data collection and analysis,decision to publish, or preparation of the manuscript