| Abstract: | Comparative genomics has identified regions of chromosomes susceptible to participate in rearrangements that modify gene order and genome architecture. Additionally, despite the high levels of genome rearrangement, unusually large regions that remain unaffected have also been uncovered. Functional constraints, such as long-range enhancers or local coregulation of neighboring genes, are thought to explain the maintenance of gene order (i.e., collinearity conservation) among distantly related species since the disruption of these protected regions would cause detrimental misregulation of gene expression. Local enrichment of certain genetic elements in regions of conserved collinearity has been used to support the existence of regulatory-based constraints, although the evidence is largely circumstantial. Indeed, a mechanism of chromosome evolution based only on the existence of fragile regions (i.e., those more susceptible to breaks) can also give rise to extended collinearity conservation, making it difficult to determine whether conserved gene organization is actually caused by functional constraints. Chromosome engineering coupled with genome wide expression profiling and phenotypic assays can provide unambiguous evidence for the presence of functional constraints acting on particular genomic regions. We have recently used this integrated approach to evaluate the presence and nature of putative constraints acting on one of the largest chromosomal regions conserved across nine species of Drosophila. We propose that regulatory-based constraints might not suffice to explain the maintenance of gene organization of some chromosome domains over evolutionary time. |
