Molecular cytogenetic dissection of human chromosomes 3 and 21 evolution

Chromosome painting in placental mammalians illustrates that genome evoluti on is marked by chromosomal synteny conservation and that the association o f chromosomes 3 and 21 may be the largest widely conserved syntenic block k nown for mammals, We studied intrachromosomal rearrangements of the synteni c block 3/21 by using probes derived from chromosomal subregions with a res olution of up to 10-15 Mbp, We demonstrate that the rearrangements visualiz ed by chromosome painting, mostly translocations, are only a fraction of th e actual chromosomal changes that have occurred during evolution. The ances tral segment order for both primates and carnivores is still found in some species in both orders. From the ancestral primate/carnivore condition an i nversion is needed to derive the pig homolog, and a fission of chromosome 2 1 and a pericentric inversion is needed to derive the Bornean orangutan con dition. Two overlapping inversions in the chromosome 3 homolog then would l ead to the chromosome form found in humans and African apes, This reconstru ction of the origin of human chromosome 3 contrasts with the generally acce pted scenario derived from chromosome banding in which it was proposed that only one pericentric inversion was needed. From the ancestral form for Old World primates (now found in the Bornean orangutan) a pericentric inversio n and centromere shift leads to the chromosome ancestral for all Old World monkeys. Intrachromosomal rearrangements, as shown here, make up a set of p otentially plentiful and informative markers that can be used for phylogene tic reconstruction and a more refined comparative mapping of the genome.