The bithorax complex in the fruit fly, Drosophila melanogaster, controls the development of 10 or more segments comprising the posterior half of the fly. The genes of the bithorax complex cause these segments to differ one from another. Animals which lack the bithorax complex develop with these segments appearing identical, all like the middle segment of the thorax. The complex is large, spanning over 300 kb, but it has only three protein coding regions. The bulk of the DNA apparently regulates the patterns of these proteins. The patterns are intricate, and they differ in each segment. The regulatory regions affecting any one segmental unit are clustered on the chromosome, and successive regulatory domains are lined up on the chromosomes in the order of the segments which they affect. The proposed experiments focus on these regulatory domains. DNA fragments from the bithorax complex have been placed next to a promoter driving the bacterial beta-galactosidase gene, and these constructs have been transformed into flies, using a P element vector. Some constructs produce beta-galactosidase in the appropriate segments, and maintain that pattern throughout embryonic development. Other constructs turn on beta-galactosidase in the correct segments, but the patterns soon spread through all the segments. Further dissection of these fragments should help us understand how a regulatory region is activated in a particular segmental unit, and how the active (or inactive) state is fixed. Recently, several labs have isolated genes homologous to those of the bithorax complex from many other organisms, from nematodes to people. The mammalian homologs are highly conserved in parts of their protein coding regions, they are expressed in comparable segmental regions of the organism, and they are arranged on the mammalian chromosomes with the same linear order. The basic body plan must be very ancient. The organism makes an array of repeated units, and then modifies them, unit by unit. The regulatory machinery to accomplish this might also be ancient so that the mechanisms discovered in Drosophila could apply to many other animals.
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