Can Fruit Flies Help Us Predict the Course of Evolution?

In popular culture, we often think of a single gene being responsible for a single physical trait. For example, in the X-Men movies, all of the X-Men have their superpowers because of a single mutant “X Gene”. In reality, the relationship between an organism’s genotype (all of its genetic information) and phenotype (what its body is actually like) is much more complex. Often individual traits are determined by a whole host of genes working together as part of a gene regulatory network (GRN). In a GRN, a single gene might act like a switch that activates a number of other genes responsible for creating a particular feature of an organism. It is thought that convergent evolution (when different species go through similar evolutionary changes) is caused by mutations at key “hotspots” in GRNs. These mutations have very specific effects and are thus less likely to have other harmful consequences for the organism. In a recent study, Kittelmann et al. tested this “hotspot” hypothesis by looking at the development of fruit flies (Drosophila melanogaster).

Flies of the genus Drosophila grow hair-like structures called trichomes on their undersides as larvae and on their legs as adults. However, some species possess a “naked valley” on the underside of their legs where trichomes do not grow. This trait has appeared independently and repeatedly in different Drosophila species. The growth of trichomes is thought to be the responsibility of the hotspot gene shavenbaby (svb; as you might guess, Drosophila gene names are often whimsical). The svb gene acts as a switch that can turn the trichome-forming GRN on or off. Sure enough, by blocking svb from functioning in larval cells, Kittelmann et al. were able to stop the formation of trichomes. However, when they tried to make adult flies grow trichomes in the naked valley of their legs by expressing svb, nothing happened. In fact, they observed that cells in the area were already producing svb, yet were still naked. Upon further examination, they noticed that the cells were expressing an unusually high amount of a microRNA (miRNAs act as ‘dimmer switches’ for gene expression) called miR-92a, which is known to block the shavenoid (sha) gene, another important trichome-forming gene activated by svb. The researchers found that by expressing miR-92a in leg cells outside of the naked valley, they were able to inhibit the formation of trichomes. This is consistent with other findings that species that have a mutant version of miR-92a, which is unable to block sha, have smaller naked valleys on their legs.

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Figure 1. A) svb is a key gene in the network responsible for forming trichomes in Drosophila larvae. B) While svb is still an important gene in the formation of leg trichomes, miR-92a also plays a key role by inhibiting sha and possibly other important genes activated by svb, halting trichome growth. Figure from Kittelmann et al. article.

So, what does this tell us about evolution?  First, it tells us that certain hotspot genes in GRNs are likely to be sites for mutation across similar species, as miR-92a is responsible for the loss of trichomes in legs across the Drosophila genus. On the other hand, it shows that GRNs act differently at different stages of development: svb is the hotspot gene for trichome formation or non-formation in larvae, but miR-92a is the hotspot on adult legs. This indicates that by studying GRNs in different organisms and identifying key genes, scientists may be able to predict evolutionary changes that are likely to occur in any species with the same GRN. This would advance our knowledge of how evolution works, and help us better understand how life came to be the way it is today.

Summary written by: Nathanael Willms

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