DAPI-stained Drosophila polytene chromosomes. Courtesy of Wen Wang and Manyuan Long, University of Chicago, USA.

In the fast-moving field of Drosophila genetics and genomics (see the reviews on pages 176 and 189 of this issue), chromosome 4, the smallest of the three autosomes, has often kept a rather low profile. Looking no bigger than a dot on metaphase spreads and with only ∼80 genes to its name, not to mention the lack of crossing over during meiosis, most labs have shunned this dull and invariable chromosome. And with good reason, right? Wrong, say Wen Wang et al., who have just published work showing that the fruitfly's fourth chromosome leads a happening life: not only does it recombine, but also it consists of blocks of highly polymorphic regions interspersed with less variable domains. Both findings suggest that, contrary to theoretical and empirical evidence, this chromosome has been evolving, albeit at different rates in different regions.

Only ∼25% of chromosome 4 is euchromatic, and it is in this portion of the chromosome that Wang and colleagues decided to look for nucleotide variation, by sequencing a 5-kb chromosome 4 region from 33 individuals taken from either worldwide or local (Israeli) fly populations. Surprisingly, in both samples, nucleotide variation was far in excess of that seen before on a chromosome 4 gene (cubitus interruptus, ci ), but was comparable with that seen on autosomes. What's more, the segregating nucleotides are organized into two haplotypes. The fact that the dimorphism occurs at all and that the frequency of each haplotype is more or less equal in local and worldwide populations probably points to the influence of balancing selection — a force that actively maintains genetic variation. Intrigued by the difference in variation at ci compared with their sample region, the authors sequenced an additional 15 regions. Their survey found that chromosome 4 is made up of three distinct domains: the region organized into haplotypes was flanked, on one side, by a variable region with no haplotype organization and, on the other, by a very homogeneous region.

What could account for the different evolutionary histories of the three domains? The authors estimate that at least six recombination events have occurred along the chromosome; if recombination were taking place at the boundaries between different domains — which is suggested by the presence of repetitive sequences — then this could be a contributing factor. However, the specific forces that give each region its characteristic variability have yet to be discovered.

Whether this revised view of the fourth chromosome will be enough to bring it out from the shadows is debatable; after all, its recombination rate might be several hundred times lower than that of autosomes. Then again, it could be a hunting ground for some more surprises.