Variations discovered in fourth chromosome of fruit fly

Researchers in Ecology & Evolution overturned a classic belief that has been published in both genetics and evolution textbooks since the 1930s, when they reported in the Jan. 4 issue of Science that the tiny fourth chromosome of the fruit fly, believed to be identical in every member of the species, actually has several regions that vary.

Manyuan Long, Assistant Professor in Ecology & Evolution, directed the study. “This classic conviction of genetics and evolution, this rock-bottom-solid conclusion, which has become a textbook example of natural selection’s propensity to eliminate variation from closely linked genes, just doesn’t hold up.”

Since 1906, Drosophila melanogaster, the common fruit fly, has been at the center of genetic research. The proof that genes exist on chromosomes like beads on a string, that they are linked together, that they can be mapped, even the method of naming genes, comes from early research on fruit flies.

The synthesis of Darwin’s theories about evolution and Mendel’s discoveries about genetics was made using fruit flies. And the discovery of recombination, in which paired chromosomes can exchange genes as they form egg or sperm cells and thus increase genetic diversity, derived from early work on the four chromosomes of the fruit fly.

Despite the fly’s century in the laboratory limelight, its tiny fourth chromosome––which contains only 1 percent of the insect’s coding DNA––has been comparatively neglected. Based on limited evidence available at the time, the pioneers, including Calvin Bridges and Nobel Prize winner Hermann Muller, determined that there were no genetic crossovers, meaning no exchange of hereditary information, on this tiny chromosome.

This belief helped to inspire elaborate theories about the consequences of a non-recombinant chromosome, introducing the concepts of “selective sweeps” and “genetic hitchhiking.” If a mutated gene on Chromosome 4 conferred a sufficient survival advantage, the experts posited, the entire advantageous chromosome, rather than the single gene, would sweep through a population, carrying along the founder’s version of every gene on that chromosome, thus eliminating all variation.

In 1991, as a graduate student in the laboratory of Martin Kreitman, Professor in Ecology & Evolution, one of the authors of the current Science paper tested the theory. Kreitman’s student, Andrew Berry (now a researcher at Harvard’s Museum of Comparative Zoology), sequenced the cubitus interruptus gene on Chromosome 4 from 10 natural lines of Drosophila melanogaster. All 10 were identical.

Long’s research team, including postdoctoral fellow Wen Wang and genetics graduate student Kevin Thornton, became suspicious, however, when Wang identified sphinx, a new gene with several variations. Sphinx was on Chromosome 4. So they analyzed the sphinx gene from Drosophila melanogaster populations from all over the world.

They found high levels of variation within this gene and in other scattered sites on Chromosome 4. The level of variation was similar to genes in regions on other chromosomes with normal levels of recombination. At least six sites on the chromosome were found to have recombination.

After looking at multiple sites from many populations, Long and his colleagues determined that Chromosome 4 could be divided into three discrete domains, a central region (including the cubitus interruptus gene) with no variation, a region farther out with low variation and the central region around sphinx, nearly 20 percent of the chromosome, with normal levels of variation.

“This indicates that the fourth chromosome is not evolving as a single unit,” note the authors. “Different regions appear to have different evolutionary histories.”

Another surprise was an unusual distribution pattern for the highly variable region. The researchers found two very different versions of this region. The ratio between the versions was consistent for fly populations from all over the world: evidence that fruit flies “must embrace diversity, even on Chromosome 4, to survive,”