In metazoans, the nuclear lamina is thought to play an important role in the 
spatial organization of interphase chromosomes, by providing anchoring sites for 
large genomic segments named lamina-associated domains (LADs). Some of these 
LADs are cell-type specific, while many others appear constitutively associated 
with the lamina. Constitutive LADs (cLADs) may contribute to a basal chromosome 
architecture. By comparison of mouse and human lamina interaction maps, we find 
that the sizes and genomic positions of cLADs are strongly conserved. Moreover, 
cLADs are depleted of synteny breakpoints, pointing to evolutionary selective 
pressure to keep cLADs intact. Paradoxically, the overall sequence conservation 
is low for cLADs. Instead, cLADs are universally characterized by long stretches 
of DNA of high A/T content. Cell-type specific LADs also tend to adhere to this 
"A/T rule" in embryonic stem cells, but not in differentiated cells. This 
suggests that the A/T rule represents a default positioning mechanism that is 
locally overruled during lineage commitment. Analysis of paralogs suggests that 
during evolution changes in A/T content have driven the relocation of genes to 
and from the nuclear lamina, in tight association with changes in expression 
level. Taken together, these results reveal that the spatial organization of 
mammalian genomes is highly conserved and tightly linked to local nucleotide 
composition.