We're all the same colour with the lights off. This sentiment is literal for many animals that live in constant darkness because the loss of the skin pigment, melanin, is commonplace. For example, certain populations of the Mexican tetra fish, Astyanax mexicanus, live in isolated underground caves that never see the light of day and have evolved to have little to no pigment in a very short time. But other populations of A. mexicanus living in sun-lit surface pools still produce normal amounts of melanin. In fact, albinism is an extremely rare condition because it leads to a host of health complications beyond a sunburn. There must be some advantage, then, to shutting off melanin synthesis in a lightless world. One intriguing explanation is the melanin–catecholamine trade-off hypothesis. Catecholamines are neurotransmitters that play a key role in brain function. Because both of these molecules are synthesized from the same amino acid, l-tyrosine, less melanin production leaves more l-tyrosine available for catecholamine synthesis. But why are cavefish willing to sacrifice melanin for a boost in catecholamines? That's what a group of researchers headed by William Jeffery from the University of Maryland, USA, wanted to find out.
Jeffery and his colleagues had a hunch that if cavefish brains had more of the catecholamine noradrenaline (norepinephrine), it might help the fish stay alert longer to seek out food and mates, both of which are in scarce supply deep underground. Noradrenaline is a stimulating neurotransmitter best known for heightening an animal's senses during stress. Jeffery already knew that it takes a lot longer for an albino laboratory mouse to succumb to anaesthesia than a regular mouse, and he faced similar challenges with his albino cavefish compared with the fully pigmented surface fish. So, the researchers used the length of time it takes a fish to reach unconsciousness under anaesthetic as a proxy for alertness and set about testing the trade-off hypothesis.
The team began by measuring noradrenaline in A. mexicanus brains and confirmed that albino cavefish brains do have more of this catecholamine than the brains of surface fish, as predicted by the trade-off hypothesis. When the team gave albino cavefish a drug to block noradrenaline receptors, they found that the cavefish's tolerance for anaesthesia decreased, meaning the cavefish struggled to stay alert without noradrenaline signalling in the brain. In contrast, when the team supplemented the pigmented surface fish with an extra dose of noradrenaline, these fish resisted the anaesthetic longer, becoming more like their albino relatives.
Jeffery's team now needed to link decreased melanin production with their observations of heightened alertness in noradrenaline-loaded brains. Albinism is caused by a mutation in a gene called oca2, which encodes a protein that regulates l-tyrosine delivery to melanin-producing cells. So, the scientists used a molecular tool to knockout the oca2 gene in surface fish, making them albino. When the researchers presented these mutated surface fish with anaesthetic, they found that it took these fish a long time to reach unconsciousness, just like in the naturally albino cavefish.
So Jeffery's group has confirmed that decreasing melanin synthesis in cavefish enables the fish's brain to make more noradrenaline from l-tyrosine, and this additional noradrenaline helps them fight off drowsiness, a great advantage for cave life. Unfortunately, we surface dwellers will have to settle for a double espresso to eke out a few more hours from the day!