Banner by Sarah Lindley

Now You See It: A Brief History of Evo-Devo

By Sarah Lindley

Every day is the same: I sit down, flip a switch, and crank the rubbery red valve until I hear mechanical whirring from the lightbox and sizzling from the carbon dioxide pad. Tap the fruit flies to the bottom of the vial and dump them on the pad in one swift arc—the ones that didn’t drown in their media, that is. Hold them there until they’re still, then push the flies around with a paintbrush to my heart’s content.  

I sort through hundreds of fruit flies a day as part of my research, but I never tire of seeing Drosophila eyes under the microscope. Bright, cherry red eyes—or sometimes white, or orange, or pink—staring back at me.  

Undeniably eyes, but so different from my own. I can stand in front of a mirror and watch my pupils contract or expand in response to light levels. In photographs, I can see my irises take on an amber overtone in the sun. They’re nothing like these absurdly colored fly eyes, which are really just hundreds of tiny eyes honeycombed together.  

Yet people and fruit flies, and basically all animals except some jellyfish and weird jellyfish-adjacent creatures, share the same key gene for the development of eyes and other neural tissues, pax6. But unlike many genes, pax6 has changed very little since these animals last shared a common ancestor. In fact, the protein sequence is identical in humans and mice. 

So when my human eyes and my fruit flies’ eyes meet each other, my mind occasionally wanders to questions larger than why don’t I work with a model organism that isn’t notorious for drowning in its own food?—How can the same gene result in such different eyes in different animals? How do developing cells “know” to eventually become a human eye, and not Drosophila eye cells? For that matter, how does any cell “know” to become anything? 

These are the questions evolutionary developmental biology works to solve. “Evo-devo” combines the study of evolutionary biology (how do structures evolve in organisms?) and developmental biology (how do structures form in developing embryos?). The field technically celebrates its official 25th anniversary this year, but really has a much longer and richer history.  

Evo-devo research suggests that the similarities in body patterning and morphological structures across the animal kingdom are in large part due to an evolutionarily conserved genetic toolkit. The toolkit consists of families of “master” regulatory genes, functioning in contexts of larger genetic regulatory networks, whose protein products essentially dictate when and where to produce certain parts of the body.  

The importance of this toolkit is underscored by several classical evo-devo experiments, which resulted in some arguably creepy yet fascinating observations. For instance, 30 years ago, researchers were able to induce growth of eyes in fruit flies by driving pax6 expression in tissues where eyes do not naturally grow. They could do this using both the fruit fly pax6 gene and the mouse pax6 gene, yet in both cases, the result was undoubtedly a fruit fly eye.  

This experiment highlights an important idea about the genetic toolkit: it just determines what, where, and when structures are created, not how. That part is left up to other genes, many of which may likely be more unique to particular organisms. This, and the differences between the particular details of when and how the toolkit is activated, can help explain why other organisms are so different from us, yet so recognizably familiar. In the card game of development, we may have different decks, but we’re following the same house rules.  

Besides Pax genes, the gene family that contains pax6 and was named after domains in their protein structures called paired boxes, another major player in the toolkit and a regular headliner in evo-devo research is the Hox family of genes. Named for their homeobox domains, Hox genes are conserved among almost all animals and are often considered master regulators of body patterning.  

Mutations in Hox genes can cause body parts to be built in the wrong places in a developing embryo. For instance, a mutation in a Hox gene called antennapedia causes an extra pair of legs to grow where fruit flies’ antennas usually form. Another mutation called bithorax causes fruit flies to grow two pairs of wings instead of just one.  Studying bithorax led to the discovery of Hox genes by Edward B. Lewis, who went on to share the 1995 Nobel Prize in physiology or medicine with Christiane Nüsslein-Volhard and Eric F. Wieschaus for the discovery of genes involved in embryonic development.  

Something unique about Hox genes is their orientation on chromosomes. Many genes’ locations appear to have no rhyme or reason; genes in related pathways are often located on completely separate chromosomes from each other. Yet in many animals, Hox genes are laid out in a row right next to each other—blueprinted in the reverse order as they are expressed in a developing embryo. Hox genes that are “downstream” on the chromosome are expressed in the head, and “upstream” genes in the abdomen, creating a polar gradient of body segments. Though there are many solid theories about this, the evolutionary reasons for this blueprint still remain unclear.    

But while I find all of these discoveries captivating, they are all at least some twenty-odd years old. Has the field of evo-devo now run its course, having told all the interesting stories it can about our evolutionary camaraderie? Does it now lay as dead as my flies when they sense a singular water molecule in their environment?  

Maybe I’m not really one to know—after all, it’s not for evo-devo purposes that I’ve spent enough days hunkered down in front of a microscope that I sometimes see flies on the back of my eyelids as I’m falling asleep. But contrary to the beliefs of some friends and family members I’ve deeply confused with slightly crazed rants about my flies, none of us “drosophilists” would do what we do if we didn’t think there was more that the flies could teach us, and that what we learn might matter outside our esoteric little circle.  

For one, the more we know about developmental biology, the more we can explore its clinical relevance for developmental disorders, such as limb formation disorders that can be caused by Hox mutations. It’s also important to know what could happen if genes that are supposed to be inactive after development stay active. For instance, gene regulation dysfunction is highly intertwined not only with developmental problems but also with cancer. Hox and Pax genes can either be oncogenic or tumor-suppressing. Lastly, the idea of conserved gene regulation networks is not limited to embryonic development, but is also hinted at in other fields, such as behavioral biology; some research suggests the possibility of a genetic toolkit underlying similar behavioral responses found in different animals.  

The evidence is overwhelming; if today you become the lord of the flies, tomorrow you may reign over the animal kingdom.  

Next time you swat some pesky fruit flies away from your ripe bananas, take a moment to appreciate your evolutionarily long, long-lost cousins, and the fact that you follow the same rules to grow, from top to bottom. (Then set up an apple cider vinegar trap, and send them on their way.)