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Evolutionary Conservation: How Tiny Life Forms Tell Us About Ourselves

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Right now there are thousands of laboratories across the globe conducting biomedical research, or that which pertains to advancing our understanding of human health and medicine. Yet despite the ultimate goal of learning more about the parameters surrounding the fitness of our fine species, much of our current knowledge comes from studying organisms that do not fall under the Homo sapiens umbrella.

In some cases, at least characteristically speaking, it's not even close. Humans are eukaryotic, multicellular organisms with advanced organ systems, but still, evolutionary conservation has made it such that a majority of cellular processes are virtually identical in many species. For instance, the basic tenet of cellular respiration (the process by which energy, in the form of adenosine triosphosphate (ATP), is created) is conserved across nearly every living thing on this planet. This, along with the enormous ethical concerns associated with using human research subjects, has allowed driven scientists to figure out the wonders of our biology using organisms such as rats, mice, fish, worms, flies, yeast, and even bacteria.

A fantastic example of how model organisms can tell us more about us comes from the laboratory of Ethan O. Perstein, a Lewis-Sigler research scholar at Princeton University. Dr. Perlstein is an evolutionary pharmacologist, which is basically a fancy way of saying that he studies how chemicals interact with cells. This is particularly relevant when discussing commonly prescribed drugs, because there are people who either do not respond to or experience unwanted side effects to these treatments.

To try to tease out some of the underlying factors involved in this response (or lack thereof) in humans, Dr. Perstein has turned to baker's yeast as a model system. Officially known as Saccharomoyces cerevisiae, baker's yeast is a commonly used unicellular organism -- and not just in a lab. Because it can live as a facultative anaerobe, meaning that it can generate energy through the process of fermentation when oxygen becomes scarce, we have been able to harness the culinary powers of yeast for the production of bread, wine, and my favorite, beer. However, because the yeast genome is quite similar to our own (they are an evolutionary predecessor), as well as the ease with which yeast can be maintained and manipulated in the laboratory, yeast has become the model organism of choice for researchers interested in discovering specific aspects of human genetics and metabolism.

For instance, in Dr. Perlstein's latest study, yeast were used to help shed light on how our cells adapt to chronic exposure to a commonly prescribed antidepressant, Zoloft. While scientists know that the modus operandi of most antidepressants occurs through some manipulation of serotonin levels, the brain chemical associated with feelings of happiness, exactly how antidepressants work is largely unknown.

Scientists hypothesize that antidepressants like Zoloft block the receptors for serotonin in the brain, which is the basis for classifying drugs like Zoloft as selective serotonin-reuptake inhibitors (SSRIs). In theory, SSRIs work by allowing more serotonin to be active in the brain, thus providing the prescribed recipient with relief from depression. However, as with everything pertaining to human biology, things are not always that straightforward.

Based on what we know from studies done in rodents and from reports from humans taking Zoloft or other SSRIs, it is clear that these antidepressants take some time to kick in. Furthermore, Zoloft appears to affect cells in a way that is completely independent of its ability to block serotonin receptors. More specifically, Zoloft has been shown to accumulate in the membranes of animal cells, which could effect nerve transmission. From these observations, some scientists have hypothesized that antidepressants like Zoloft can affect cells in multiple ways, and that these effects go beyond the transport of serotonin.

By using yeast, which do not have receptors for serotonin, Dr. Perlstein and his team were able to examine the effects of Zoloft that are unrelated to the traditionally hypothesized mechanism of SSRIs. They showed that Zoloft affects yeast membranes and turns on a pathway that helps protect cells by recycling excess or damaged membranes. According to Dr. Perlstein, "[this] work provides some grounding for the neurotrophic hypothesis of depression, which states that the loss of neural connectivity in specific brain regions such as the hippocampus may actually be the root of depression." In other words, depression may involve an actual disruption of nerve cell networks and not just low activity levels of brain chemicals like serotonin.

This research is helping to redefine the biological basis of depression in humans, which, in turn, will help scientists develop new and more effective treatments. And it was done using yeast.

There are countless examples of this sort of thing, and if I tried to list them all, I'd be here all day. But I will take this opportunity to say a few quick thank-yous nonetheless: Thanks to worms (Caenorhabditis elegans) for giving us insight into the molecular mechanisms surrounding our longevity. Thanks to fish (Danio rerio) for letting us study the process of embryonic development. A solid muchas gracias to flies (Drosophila melanogaster), which are the most widely used model in biology, for helping us figure out human genetics. And of course, big up to yeast for their multiple contributions, including that which gave Sir Paul Nurse his 2001 Nobel Prize in physiology and medicine.

This is an extremely short list highlighting how we can look to other organisms to learn more about ourselves. If this genetic relatedness and conservation of basic biological processes isn't evidence for evolution, I don't know what is!

So the next time you pop a pill to help you find relief from some ailment, the person to thank might not actually be a person, and to me, that's just incredible.