Nobel in Chemistry for an Evolutionary Revolution

The Nobel Prize awarded to Dr. Arnold, Dr. Smith, and Dr. Winters

Evolution, the process of gradual changes to genetic information in each generation over millions of years, proposed by Charles Darwin in the 19th century is being revolutionized by modern science. Unexpectedly, the revolution is driven not by evolutionary biologists or ecologists, but rather centered around the methodologies of chemists and enzymologists.

Accumulation of mutations is a slow and random process. However, scientists were able to harness the power of evolution to identify and select for specific mutations that improve the ability of molecules of interest. This year’s Nobel Prize in Chemistry was awarded to Dr. Frances Arnold “for the directed evolution of enzymes” and to Dr. George Smith and Dr. Gregory Winters “for the phage display of peptides and antibodies.”

Dr. Arnold was able to develop a methodology to enhance enzyme activity and give existing enzymes new functionality, a feat that was realized in unprecedented amount of time. She was able to accomplish this by simply using error prone PCR to cause mutations in enzymes and then selecting one with favorable ability compared to the many enzymes produced. Repeating the cycles hundreds of times enhancing the functionality of the enzyme each time, allowed her to develop P450 with novel function.

Dr. Smith was also able to apply the concepts of evolution by using bacteriophages, viruses that normally infect bacteria. Dr. Smith developed the process of phage display, a means to study protein-protein interactions by encoding genetic information into bacteriophages. By using E. coli cells infected with bacteriophages and then infecting with another virus, Dr. Smith was able to encode genetic information of a protein on to the viral coat of bacteriophages. This allowed the new protein to be displayed on the viral coat and able to be recognized with an antibody.

Dr. Winters then incorporated the antibody gene rather than a specific protein into the viral coat. This allowed him to scavenge for antibodies with a specific binding site via interactions with different antigens. Using a similar method to Dr. Arnold, he caused mutations in the antibody, and selected for the antibody with highest affinity to the antigen. The results were highly efficient antibodies and a mechanism that is used to produce 11 out the 15 most-sold drugs on the planet.

Peer edited by Rachel Battaglia.

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A World Without Cheese

Imagine a world without pizza, nachos, cheeseburgers, mozzarella sticks, macaroni and cheese; a world without cheese.

The significance cheese goes well beyond its delicious taste.
From: Leon Brocard.

Living in a world with thousands of cheeses from many countries and cultures, it is difficult to imagine there was a time in human history when cheese did not exist. Some of us cheese lovers might even feel a little faint thinking about the so-called cheese-less time. Thankfully, new research suggests the dark time before cheese may be shorter than originally thought. Remnants of cheese fats were found in pottery in Croatia that date back to between 6000 and 5000 B.C. Previous studies suggested cheese did not arrive in the Mediterranean until 3000-1200 B.C.; about 3000 years later! The development of cheese making in these ancient villages may have decreased mortality rates in children and aided in the evolution of dairy tolerance, so we can eat our favorite cheeses today.

You might be wondering, how do you identify cheese remnants that are over 7000 years old? The secret lies in fat. Most foods (whether from plants or animals) contain fat, and anyone who has tried to lose weight can tell you fats are difficult to make disappear, allowing them to withstand the test of time. Fats are made up of chains of carbon, an element that is found in all life on Earth. There are three types of carbon that occur in nature, collectively called carbon isotypes. In fats, carbons are attached in chains that can vary in their length. By looking at variations in chain length and the carbon isotype found in the fat, scientists can determine where the fat came from; meat, vegetables/plants, or dairy. Furthermore, scientists can even determine if the fats are from fermented dairy products, such as cheese. Using this technology, the scientists identified fats in ancient pottery discovered in Croatia that are likely from cheese. A similar technology that looks at what makes up proteins, instead of fat, was used to identify the oldest solid cheese, which was found in an Egyptian tomb earlier this year.

The ability of an individual to eat cheese and increase their chance of survival to adulthood could lead to a population with more people who are able to eat cheese over multiple generations. This diagram assumes everyone who lives to adulthood has three children with the same “cheese-eating status” as their parent.

While many of us might think the significance of cheese lies in the ability to enhance our food with its melty, cheesy goodness, the impact of cheese-making on ancient peoples was likely more significant. Cheese would have provided vital protein, calories, and fat for people in ancient villages, especially during winter or times of famine and disease. Scientists also think the high protein and calorie content in cheese would have been a great source of nutrition for children and likely aided in their survival to adulthood. Furthermore, the advent of cheese-making in these ancient villages probably aided in the evolution of humanity’s ability to eat dairy. People living in ancient times were lactose intolerant. Because cheese contains less lactose than milk or other dairy products, it is likely people in 5000 B.C. could tolerate small amounts of cheese. However, if children who could eat more cheese were more likely to survive to adulthood and then have children who could also consume larger amounts of cheese, over time the people in these villages would become able to eat more and more cheese (see diagram above). Over the course of thousands of years, the human population would evolve to be able to eat food with more lactose, such as milk or ice cream.

A world without cheese would surely be a less tasty one, but the more we learn about the origins of cheese, the more it seems that a world without cheese would not be the world we know today.

Peer edited by Rita Meganck.

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Are female túngara frogs better at learning than males because of how they breed?

Image from Alexander T. Baugh (Encyclopedia of Life)

A female (above) túngara frog chooses a male (below) to mate with based on his call. Although it is difficult to tell, these frogs are small enough to fit on a quarter!










As Charles Darwin was the first to document, the behavior, physical features and sexual activities of species. These observations can frequently be understood through the lens of thousands or even millions of years of natural selection. Random genetic changes arise and organisms become “mutated,” so to speak. In turn, organisms with the best-suited characteristics for their environment (which of course, can also change and set things back to square one!) are more likely to survive and continue to reproduce and populate their current environment.

Most people tend to associate these adapted characteristics with the famous beaks of Darwin’s finches, or maybe the hilariously long necks of giraffes. But one often overlooked feature is the brain. The control center of behavior, albeit quite enigmatic in how it operates, functions due to the coordinated firing of many small units known as neurons. The characteristics of the brain that are most interesting to me are cognitive abilities, specifically, the abilities of learning and memory. Superior learning and memory abilities may be selected for within a species for various reasons. For instance, the black-capped chickadee (Poecile atricapilla) can be found all over North America, from Alaska to Colorado. When birds from these areas were behaviorally assessed and their brains were compared, it turned out that birds from Alaska were more efficient at hiding and finding food, in addition to having larger hippocampi – the area of the brain responsible for long-term memory (Pravosudov & Clayton, 2002, Croston et al. 2015). What’s the proposed reason for this? Alaskan birds needed to be better than Coloradan birds at saving food during the summers then finding it later to survive their longer winters (Pravosudov & Clayton, 2002, Croston et al. 2015).

These differences in brainpower aren’t just explained by food hoarding habits though! They can also be observed in the polygamous meadow voles (Microtus pennsylvanicus). Males exhibit an increased ability for spatial memory over females likely due to their breeding behavior. The promiscuous males greatly expand their home ranges in order to seek out and breed with a multitude of females (Gaulin & FitzGerald, 1989). As expected, male voles have comparatively larger hippocampi than female voles (Jacobs et al., 1990) and perform better on spatial memory tasks (Gaulin, FitzGerald & Wartell, 1990).

As these natural ecological differences within species are recognized, it continues to provide credence to the idea that learning and memory skills can adapt within species while most other characteristics remain the same. This idea led to the túngara frog (Physalaemus pustulosus), whose mating behaviors rely solely on the female’s assessment and choice of males. While males remain stationary in a breeding pond and produce breeding calls, females visit multiple males before ultimately deciding on a mate (Ryan, 1985). In turn, females that are able to better recall the locations of particular males in a pond will be more successful in finding the best possible male (Ryan, Akre, & Kirkpatrick, 2009). These frogs have had to mate for millions of years and certain characteristics have become selected for within the species. It makes sense that female túngara frogs have adapted to have greater spatial memory and cognitive abilities than males. But do carefully controlled learning experiments justify this claim?

Since we can’t go back and observe this process happening over the many millions of years, the next best option is to attempt to gauge for ourselves whether or not this theory may be valid. Unsurprisingly, it is not a simple task to assess memory and cognitive abilities in animals with brains that are smaller than a pea. The first experiments done to test this utilized the simplest possible method in order to see if frogs could distinguish between two colors to learn how to escape a two-arm maze (Liu & Burmeister, 2017).

The purpose of this experiment was to train frogs to associate the reward of exiting a bright and arid maze (not an idea environment for a nocturnal rainforest habitat!) with the red door that allowed them to exit the maze and return to their shaded enclosure. Results showed that although female frogs learned to exit the maze using the red door, male frogs didn’t respond to the color of the door at all, instead preferring to rely on turning either right or left, and performing as well as females when they were able to use these turning cues to turn the same direction in consecutive trials.

Image from Liu & Burmeister, 2017.

A schematic diagram of the two-choice maze used in these experiments.


That’s confusing – males can only remember how to turn left or right but ignore colors? Does this mean that females can learn better after all? Seeking to explain that question, I replicated this original experiment for my thesis research, using twice as many frogs and removing the ability to use turn cues at all. Instead, frogs were released in a random orientation for every single trial. As expected, the frogs learned to exit the maze, but unexpectedly, both males and females alike learned the maze at the same rate of success. It seemed that male frogs were in fact not ignoring the colors at all, but perhaps simply reluctant to pay attention to colors if they were able to simply turn left or right and remember their last turn direction.

Although I saw that males and females could demonstrate their ability to learn a simple color association, a strange pattern emerged in my experiment. In training half of my frogs to use the red door and the other half to use the yellow door, it seemed that the frogs trained to the red door were more successful than their yellow door brethren. I sought to address this bias in a follow up experiment by removing colors entirely and instead utilizing monochromatic patterns. Although frogs are known to be able to see black and white, it seemed that the chosen patterns were not distinct enough for the frogs, and they failed to show evidence of learning.

Something that a lot of people don’t realize about science is how many failures could possibly be hiding behind the triumphant headline of a successful result. Despite the questions of whether or not there is a sex difference in the ability to learn in túngara frogs, it is clear at this point that the distinction is not as cut and dry as it was once thought to be. Follow up experiments will aim to elucidate the differences between male and female túngara frogs, by continuing to seek possible answers (or maybe produce more questions…) using improved black and white cues, auditory cues, and removing all cues but turning cues. Although our understanding of how evolutionary mechanisms can alter the attributes and abilities of the brain is still in need of significant contributions, these experiments show that even without access to a DeLorean, it is still possible to work towards elucidating our evolutionary past.

Peer edited by Emma Hinkle.

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