One Large Plague Against Humanity, One Small Step Towards Immunity

By: Linda Huang, Shivani Seth, Shawn Kripalani, Anasua Bandyopadhyay and Nikita Maddineni

Imagine you’re living in the middle ages welding steel swords, leading your mundane life. Suddenly, your child is overcome with a horrid fever. Distraught, you also start to notice your child developing shockingly large lumps all over his body. What is going on? Soon, you learn that this nightmare is not only endangering your son’s life, but also the communities around you. Two weeks later, everyone around you has passed away, but for some reason you managed to survive. Why?

This so-called curse was actually known as the Black Plague that spread throughout Europe. The black death killed 75 to 200 million people and it peaked in Europe between the years of 1346 and 1353. It began with a rat infected with the bacterium Yersinia pestis. The bacteria infect humans by attacking the lymph nodes. They then begin to rapidly replicate, causing the lymph nodes to swell and become buboes. These buboes cause the immune system to go into septic shock, which is multiple-organ failure. This was one of the darkest points of European history, as 30-60% of Europe’s total population was killed. The methods of treatment ranged from visiting witch doctors to bathing in urine to turning to the church. Communities even started to live in the sewage systems after they became aware that it could be airborne. However, there was a small percentage of the population that was able to survive the plague.  In the population that survived, researchers found that there was a mutation in the gene for the CCR5 cell membrane receptor called CCR5-∆32.

This is an example of natural selection, where the bubonic plague acted as the selection pressure for individuals with the mutation. These individuals with the delta-32 mutation had a higher fitness because they were able to survive and reproduce better compared to individuals who were susceptible to the black plague.

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Figure 1: Top map shows regions of Europe during the black plague where the CCR5-∆32 mutation was present vs. regions where it was not present. Bottom map shows regions of Europe that were affected by the Black Plague vs regions that were not.

Coincidentally, research has shown that this mutation can also provide protection against HIV infection. In order for HIV to enter cells, the CCR5 receptor must be present on the surface of the cell. However, in individuals with the CCR5-∆32 mutation, the CCR5 receptor is not present on the cell membrane. Due to this mutation, individuals are resistant to HIV. This relationship between HIV and the CCR5-∆32 mutation is a way to debunk the misconception that all mutations are detrimental. In this case, having the mutation leads to increased fitness.

The protective effects of the CCR5 delta32 mutation against HIV infection are also being investigated as a potential long-term treatment option. Currently, antiretroviral therapy (ART) is the most widely used treatment for HIV, consisting of a combination of drugs that suppress progression of the disease and for reduce rates of transmission. However, ART is not a cure and individuals must rely on daily drug regimens for the entirety of their lives. Furthermore, the virus can eventually develop resistance to ART, leading to a need for more long-term treatment options.

In 2009, Hutter and other researchers identified an innovative approach using stem-cell transplantation. In a case study, a patient had HIV infection for ten years and acute myeloid leukemia. Researchers performed a stem-cell transplantation from bone marrow from an immune-compatible donor whose cells lacked expression of CCR5. The donor, who was homozygous for the CCR5 delta32 mutation, was resistant to the HIV infection. Researchers hoped that transplanting these cells with the mutation to the HIV-infected patient would confer resistance. After two transplantations, there was no recurrence of leukemia or detectable HIV in the bloodstream. The CD4+ T-cells in this patient have returned to the normal range and all carry the donor’s CCR5 gene. This patient has remained without any evidence of HIV infection for more than 8 years after discontinuation of ART, providing encouragement for stem cell transplantation as a more long-term treatment for HIV.

Normal cell that has the CCR5 receptor. HIV can enter and infect the cell.

Figure 2A: Normal cell that has the CCR5 receptor. HIV can enter and infect the cell.

Figure 2B: Mutated cell without the CCR5 receptor. HIV is not able to enter and infect the cell, thus making the individual immune to the virus.

Figure 2B: Mutated cell without the CCR5 receptor. HIV is not able to enter and infect the cell, thus making the individual immune to the virus.

To learn more:

Petz, L.D., et al. 2015. Progress toward curing HIV infection with hematopoietic cell transplantation. Stem Cells Cloning 8: 109-116.

Cohn, S.K., & Weaver, L.T. 2006. The Black Death and AIDS: CCR5-Δ32 in genetics and history. Q J Med 99: 497-503.

Allers, K., et al. 2011. Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation. Blood 117(10): 2791-99.

Galvani, A.P., & Slatkin, M. 2003. Evaluating plague and smallpox as historical selective pressures for the CCR5-Δ32 HIV-resistance allele. PNAS 100(25): 15276-79.

Shariff, Mohammed. “10 Crazy Cures for the Black Death- Listverse.” List verse. N.p., 21 Jan. 2013. Web. 06 Dec. 2015.

Libert, F., et al. 1998. The CCR5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe. Human Molecular Genetics 7(3): 399-406.

Stumpf, M.P., & Wilkinson-Herbots, H.M. 2004. Allelic histories: positive selection on a HIV-resistance allele. Trends in Ecology and Evolution 19(4): 166-8.

Hutter, G., et al. 2009. Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation. New England Journal of Medicine 360: 692-698.

Evolution of Photsynthetic Sea Slugs

Contributed by Alexandria Albert and Gavon Broomfield

Bright green sea slugs that behave like plants!                                                                 Sea slugs are a diverse family of marine gastropod mollusks characterized by their soft bodies and lack of external shell. Approximately 2,300 species have been documented, all with different physical colorations that allow them to better interact with other organisms and underwater conditions. Sacoglossan sea slugs have mastered the art of kleptoplasty by extracting chloroplasts from various algal food sources and preserving them in digestive tissue, thus creating the kleptoplast. Exploring this symbiotic interaction has provided insight into multiple evolutionary processes. For example horizontal gene transfer, the transfer of genes from one species to another, in this case from the algal nucleus to sea slug cells, has facilitated the long-term use of the kleptoplasts (Cruz et al. 2013). There are still questions about the maintenance of kleptoplasts living in animal tissue, but benefits from this form of energy production have been documented.  

 E.crispate NEWE.viridis NEW

So how is it possible that sea slugs have chloroplasts? Aren’t chloroplasts only in plants?  The key to photosynthetic capable sea slugs is symbiosis. Algal nuclear genes in the sea slug digestive cells encode for chlorophyll synthesis, giving slugs green coloring, and chloroplast proteins, which later become incorporated into the slug’s DNA to get passed onto offspring. For some species of Sacoglossa, these internal or endosymbiotic chloroplasts can be maintained long-term if the slug possesses the nuclear DNA required for photosynthesis. For other species, continual feeding on algae is necessary for long-term, sustained kleptoplastic ability. Cool, right? Since the chloroplast is not native to the sea slug, important behavioral, morphological, and biochemical adaptations have evolved to maintain this symbiosis and kleptoplasty (Schwartz, Curtis, and Pierce 2014, Schmitt, Valerie, et al. 2014). 

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So how do these photosynthetic sea slugs use these chloroplasts?                               Sea slugs adjust their parapodial lobes, lateral fleshy protrusions on their bodies used for movement, to manage light harvesting. When the parapodial lobes are extended, chloroplasts are exposed to direct sunlight which is then used as an energy source, a process known as phototrophy, as seen in plants. When doing this, sea slugs often resemble leaves. This leaf-like appearance aids in camouflage and avoidance of ocean-floor predators like crab, lobster, and fish (Schmitt and Wägele 2011). This unique behavioral adaptation has evolved to retain endosymbiotic chloroplasts.


Does this really work?                                                                                                   Studies have shown high levels of fitness benefits to kleptoplasty in Sacoglossa when measuring growth efficiency with trade-offs dependent upon algae diet and light exposure (Baumgartner, Pavia, and Toth 2015).  This adaptation has some limitations and may depend upon sunlight exposure and the species of algae. Too much sun exposure could cause photo-oxidative stress on kleptoplasts and decrease the rate of energy production over time (Serôdio, João et al. 2014).

For more information about the photosynthetic qualities of sea slugs, consult these sources:

  1. Baumgartner, Finn A., Henrik Pavia, and Gunilla B. Toth. “Acquired Phototrophy through Retention of Functional Chloroplasts Increases Growth Efficiency of the Sea Slug Elysia Viridis.” Ed. Erik Sotka. PLoS ONE 10.4 (2015): e0120874. PMC. Web. 6 Nov. 2015.
  2. Goodheart, J. A., Bazinet, A. L., Collins, A. G., & Cummings, M. P. (2015). Relationships within Cladobranchia (Gastropoda: Nudibranchia) based on RNA-Seq data: an initial investigation. Royal Society Open Science, 2(9), 150196.
  3. Schmitt, Valerie, and Heike Waegele. “Behavioral adaptations in relation to long-term retention of endosymbiotic chloroplasts in the sea slug Elysia timida (Opisthobranchia, Sacoglossa).” Thalassas 27.2 (2011): 226-238.
  4. Schwartz, Julie A., Nicholas E. Curtis, and Sidney K. Pierce. “FISH labeling reveals a horizontally transferred algal (Vaucheria litorea) nuclear gene on a sea slug (Elysia chlorotica) chromosome.” The Biological Bulletin 227.3 (2014): 300-312.
  5. Schmitt, Valerie, et al. “Chloroplast incorporation and long-term photosynthetic performance through the life cycle in laboratory cultures of Elysia timida (Sacoglossa, Heterobranchia).” Frontiers in zoology 11.1 (2014): 5.  
  6. Serôdio, João et al. “Photophysiology of Kleptoplasts: Photosynthetic Use of Light by Chloroplasts Living in Animal Cells.” Philosophical Transactions of the Royal Society B: Biological Sciences 369.1640 (2014): 20130242. PMC. Web. 6 Nov. 2015.

Systematic Penguin Evolution

Contributed by: Oceana Hopkins, Arooj Khalid, Kevin Lu

The core idea of modern evolutionary theory is that all life is descended from a common ancestor. Though the theory garners much scrutiny and skepticism, it can be explained in part through the simple mechanism of natural selection. Natural selection takes advantage of the variability that exists within the genome. Random mutations that occur in the genome are behind these variations and sometimes change the fitness of an organism. Natural selection dictates that those with higher fitness survive and reproduce; thus, certain traits are selected for within the species. This process explains how gradual change occurs and how complex organisms arise from simplistic ancestors. A common misconception regarding evolution is that life evolved randomly, or by chance. This misconception could arise because of the random nature of mutations that promote variability. Though randomness is an important component to evolutionary theory, natural selection and survival of those who are more biologically fit make sure that the process is non-random.

Known for their characteristic black and white “tuxedos”, penguins are an aquatic, flightless bird found in both warm and cold climates. Because such a large part of their lives are spent in the water, certain species of penguins will only exit the water to shed their feathers or to mate. Spending nearly 75% of their lives in the water foraging for food, penguins have developed very specific traits optimized for swimming.  Utilizing their strong forelimbs to propel their large bodies through the water, penguins have undergone very specific evolutionary changes that allow this mechanism to run smoothly. As discussed in Michael Habib’s paper on structural evolution, the strength of the bones in the forelimbs are significantly greater than that of birds who do not exhibit aqua-flying behavior (2009). In conjunction with increased bone density, more muscle mass also developed and aided in keeping the penguins warm in their cold feeding environment.

Closer inspection of the features that aid water-feeding behavior provides more evidence that disputes the misconception that evolution is random. As seen in 2006 by Slack and colleagues, macroevolution within penguins based on their fossils and mitochondrial genes was tracked and recorded. The evidence showed that the penguins’ bodies gradually adapted to the cold feeding environment over many generations. Additionally, researchers Thomas and colleagues observed in 2010 that cold water penguins have a flow of heat along their wings that originates from the brachial artery called the humeral plexus.  This vascular countercurrent heat exchanger (CCHE) provides penguins the opportunity to forage in cold water by limiting heat loss through the flippers. Scientists identified this adaptation through fossil evidence and, upon further research, learned it evolved after penguins lost the ability of aerial flight. Researchers have proposed the CCHE evolved to help balance the energy costs of longer foraging times, since the oceans were significantly cooler than penguin body temperature. Ultimately, researchers have concluded that the humeral plexus was instrumental in allowing penguins to be water feeders in subaquatic environments.


To learn more:

Clarke, J. A., D. T. Ksepka, R. Salas-Gismondi, A. J. Altamirano, M. D. Shawkey, L. D’alba, J. Vinther, T. J. Devries, and P. Baby. “Fossil Evidence for Evolution of the Shape and Color of Penguin Feathers.”Science 330 (2010): 954-57. Print

Fordyce, R. E. and Jones, C. M. 1990. The history of penguins, and new fossil penguin material from New Zealand. Pages 419-446 in Davis, L. S. and Darby, J. D. (editors), Penguin biology. Academic Press, San Diego. 467 p.

Habib, Michael. “The Structural Mechanics And Evolution Of Aquaflying Birds.” Biological Journal of the Linnean Society 99 (2009): 687-98. Print.

Stack, Kerryn E., Craig M. Jones, Tatsuro Ando, G. L. Harrison, R. Ewan Fordyce, Ulfur Arnason, and David Penny. “Molecular Biology and Evolution.” Early Penguin Fossils, Plus Mitochondrial Genomes, Calibrate Avian Evolution. Oxford Journals, Mar. 2006. Web. 13 Nov. 2015.

Subramanian S, Beans-Pico´n G, Swaminathan SK, Millar CD, Lambert DM. 2013 Evidence for a recent origin of penguins. Biol Lett 9: 20130748.

Thomas, D. B., D. T. Ksepka, and R. E. Fordyce. “Penguin Heat-retention Structures Evolved in a Greenhouse Earth.” Biology Letters 7 (2010): 461-64. Print.

Cancer: Evolutionary Fact or Fiction?

Contributed by Nicholas Eyrich, Jordan Feltes, Eric Ni, Somnath Das, Noah Steigelfest, and Evan Dackowski.

Cancer Heredity

Misconception: It is commonly perceived that cancer is hereditary, and one can either not have cancer in their family, thinking they are fine or have family members diagnosed and think it is a matter of time before they contract the disease.

Truth: Both of these notions grossly overlook the fact that most cancers are sporadic, meaning their onset is not due to family history, but rather due to gen1etic mutations and environmental exposures during one’s lifetime. Cancer is not heritable, but a predisposition to the disease can be (Peltomaki, 2012). For example, in our DNA we have two copies of each tumor suppressor gene, one from each parent. These genes keep cells from growing uncontrollably. So to lose function, one has to have mutations in both copies. Unfortunately, one can be born with a mutation in one copy, such as in Retinoblastoma (Rb). This means the gene is still expressed using the normal copy, but this confers a 50% increased predisposition for the disease bringing cells halfway closer to being cancer cells (Price et al., 2014).

Evolutionary Cancer Mutations

Misconception: It takes one bad mutation in one cell to get cancer, and cancer is one disease with all of cells in a tumor being equal.

Truth: Population biology is used to describe tumor growth and spread (metastasis), rather than arising from a single “bad” cell. Actually, it takes on average six to seven cumulative mutations (less in pediatric cancers) to confer disease, each one having been selected for during the previous cell generation. When mutations happen and build upon each other, the combination of changes can lead to cancer. (Yamamoto, Nakamura, & Haeno, 2015). Illustrated below. This supports cancer mostly being a disease of old age, as mutations take time to accumulate. Cancer essentially consists of many diseases that continue to harass the brains of researchers. Essentially, doctors have been able to treat for certain mutations, but once one important mutation is treated, another one can take over to drive relapse (Landau et al., 2015). Also, in tumors there ar2e different environments around cells fostering different mutations in various areas of the same tumor (Hardiman et al., 2015). Cancer is adapting to therapies that target mutations, making it so difficult to control.

DNA Damage

Misconception: DNA damage is rare, and we have little protection against it. Most cancer-causing agents (carcinogens) are processed chemicals not naturally found in nature.

Truth: DNA damage happens many times per day and our bodies have also evolved repair mechanisms in response to the need to correct such damage. In addition, the vast majority of cancer causin3g agents are naturally occurring substances we encounter on a daily basis (Bauer, Corbett, & Doetsch, 2015). The human body has evolved ways to counteract DNA-damaging events, for example during sunlight exposure, using molecular machinery and likewise other naturally occurring compounds (Nishisgori, 2015).



Bauer, Nicholas C., Anita H. Corbett, and Paul W. Doetsch. “The Current State of Eukaryotic DNA Base Damage and Repair.” Nucleic Acids Res Nucleic Acids Research (2015): n. pag. Web.

Hardiman, Karin M., Peter J. Ulintz, Rork D. Kuick, Daniel H. Hovelson, Christopher M. Gates, Ashwini Bhasi, Ana Rodrigues Grant, Jianhua Liu, Andi K. Cani, Joel K. Greenson, Scott A. Tomlins, and Eric R. Fearon. “Intra-tumor Genetic Heterogeneity in Rectal Cancer.” Lab Invest Laboratory Investigation (2015): n. pag. Web.

Landau, Dan A., Eugen Tausch, Amaro N. Taylor-Weiner, Chip Stewart, Johannes G. Reiter, Jasmin Bahlo, Sandra Kluth, Ivana Bozic, Mike Lawrence, Sebastian Böttcher, Scott L. Carter, Kristian Cibulskis, Daniel Mertens, Carrie L. Sougnez, Mara Rosenberg, Julian M. Hess, Jennifer Edelmann, Sabrina Kless, Michael Kneba, Matthias Ritgen, Anna Fink, Kirsten Fischer, Stacey Gabriel, Eric S. Lander, Martin A. Nowak, Hartmut Döhner, Michael Hallek, Donna Neuberg, Gad Getz, Stephan Stilgenbauer, and Catherine J. Wu. “Mutations Driving CLL and Their Evolution in Progression and Relapse.” Nature 526.7574 (2015): 525-30. Web.

Nishisgori, Chikako. “Current Concept of Photocarcinogenesis.” Photochem. Photobiol. Sci. 14.9 (2015): 1713-721. Web.

Peltomäki, Päivi. “Mutations and Epimutations in the Origin of Cancer.” Experimental Cell Research 318.4 (2012): 299-310. Web.

Price, E. A., K. Price, K. Kolkiewicz, S. Hack, M. A. Reddy, J. L. Hungerford, J. E. Kingston, and Z. Onadim. “Spectrum of RB1 Mutations Identified in 403 Retinoblastoma Patients.” Journal of Medical Genetics 51.3 (2013): 208-14. Web.

Weinberg, Robert A. The Biology of Cancer. New York: Garland Science, 2007. Print.

Yamamoto, Kimiyo N., Akira Nakamura, and Hiroshi Haeno. “The Evolution of Tumor Metastasis during Clonal Expansion with Alterations in Metastasis Driver Genes.” Sci. Rep. Scientific Reports5 (2015): 15886. Web.


Helicobacter pylori and you.

Contributed by Thomas Partin and Austin Piccolo

Species do not live in a world separate from each other. Organisms interact with other organisms everyday, and over time adapt to each other accordingly. Often, the evolution of two species can become strongly linked to each other, for better or worse. Heliobacter pylori is a bacteria that thrives in the acidic conditions of the human stomach. It causes stomach ulcers and is strongly correlated with gastric cancer. As recently as the 1980’s, the idea of a bacteria being able to survive in the stomach’s harsh conditions and being responsible for this disease was so controversial that it took one doctor intentionally infecting himself to prove its role in stomach ulcers. That doctor later won the Nobel prize in medicine for his work.

H. pylori did not first start infecting humans in the 80’s though. H. pylori and humans have been living (and battling) together for millennia. The earliest humans also played host to H. pylori. One way this can be shown is a creative use of a phylogenetic tree. Scientists sampled many different strains of H. pylori, and used them to create an ancestral tree of the different strains. They then compared the tree they made to geographic locations of their samples. What they found was that lineages of H. pylori matched perfectly with the migration patterns of ancient humans as they moved out of Africa. Newer strains of H. pylori are found where humans migrated to most recently. The strains were carried and dispersed based on how early humans moved around the globe.

This intimate relation between H. pylori and humans provides a great opportunity to explore coevolution. Humans and H. pylori have been locked in an arms race for thousands of years. H. pylori colonization poses serious health consequences to the host, which creates a selective pressure for humans that can prevent H. pylori infection. Likewise, the human body is an incredibly hostile environment towards foreign invaders like H. pylori, which creates a strong selective environment for H. pylori cells that can overcome human defenses. There is evidence this selective pressure is so strong that H. pylori begins adapting specifically to the host after initial colonization. Although not an innate aspect of human biology, antibiotics are another human defense against H. pylori. Antibiotic use creates a selective pressure for H. pylori that is so strong that resistant strains can develop remarkably quickly after attempted treatment.

Please watch the below video to learn more!;

For further information see:

Linz, B., Ballouxm, F., Moodley, Y., Manica, A., Liu, H., Roumagnac, P., Falush, D., Stamer, C., Prugnolle, F., van der Mer, S.W., Yamaoka, Y., Graham, D.Y., Perez-Trallero, E., Wadstrom, T., Suerbaum, S., Achtman, M. 2007. An African origin for the intimate association between humans and Helicobacter pylori. Nature 445: 915-918

Gao, W., Cheng, H., Hu, F., Li, J., Wang, L., Yang, G., Xu, L., Zheng, X. 2010. The Evolution of Helicobacter pylori Antibiotics Resistance Over 10 Years in Beijing, China. Helicobacter. 15: 460-466.

Oh, J.D., Kling-Bäckhed, H., Giannakis, M., Xu, J., Fulton, R.S., Fulton, L.A., Cordum, H.S., Wang, C., Elliott, Glendoria., Edwards, J., Mardis, E.R., Engstrand, L.G., Gordon, J.I. 2006. The complete genome sequence of a chronic atrophic gastritis Helicobacter pylori strain: Evolution during disease progression. PNAS. 103: 9999-10004.

Blecker, U., Landers, S., Keppens, E., Vandenplas, Y. 1994. Evolution of Helicobacter pylori Positivity in Infants Born From Positive Mothers. Journal of Pediatric Gastroenterology and Nutrition. 19: 87-90

Kennemann, L., Didelot, X., Aebischer, T., Khun, S., Drescher, B., Droge, M., Reinhardt, R., Correa, P., Meyer, T.F., Josenhan, C., Falush, D., Suerbaum S. 2011. Helicobacter pylori genome evolution during human infection. PNAS. 108: 5033-5038.

Marshall, B.J., Warren, J.R. 1984. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulcers. The Lancet. 323: 1311-131.

Avasthi, T.S., Devi, S.H., Taylor, T.D., Kumar, N., Baddam, R., Kondo, S., Suzuki, Y., Lamouliatte, H., Mégraud, F., Ahmed, N. 2011. Genomes of Two Chronological Isolates (Helicobacter pylori 2017 and 2018) of the West African Helicobacter pylori Strain 908 Obtained from a Single Patient. Journal of Bacteriology. 193: 3385-3386.

The Evolution of Bitter Taste

Contributed by Jonathan Adcock, Hana Ahmed, Robert Bruner, Farhan Momin, Andrew Shibata

How Bitter Taste Works

Specialized bitter taste receptors are concentrated at the back of the tongue. Upon eating a bitter food, these receptors are activated, and and a signal is sent to to the brain that leads to the perception of a bitter taste. Bitter taste receptors are encoded by the TAS2R gene family. This family includes nearly 25 genes and psuedogenes (genes that are no longer functioning) that are concentrated in bundles on chromosomes 3, 5, and 7. Extensive studies have been performed in order to determine which molecules in bitter foods can activate these receptors. Scientists have found that many of the compounds that activate the bitter taste receptors are chemicals produced by plants. Many of these compounds were also found to be toxic and if consumed could lead to illness or death.

How Bitter Taste Evolved

Our ancestors and other animals have not always been able to taste bitter foods. The bitterness sensation is thought to have evolved 200 million years ago. The prevalent hypothesis is that bitter taste evolved by random gene mutation events which caused the formation of the TAS2R gene family and the bitter taste receptors on the tongue that could bind to toxic chemicals. Animals possessing these mutations were able to  taste toxins in their food. These toxins would have tasted bad to the animal, and thus, the animal would learn to avoid the toxic food in the future. Animals with the mutations that produce the TAS2R gene family would be be better adapted to their environment because they can avoid toxic and poisonous foods that could cause sickness or death in the animal. Animals not possessing these mutations would still be susceptible to ingesting naturally occurring poisonous chemicals. Because these animals have improved survivability in comparison to other animals without the TAS2R genes, animals that could taste bitter foods would be better able to reproduce and pass the functional TAS2R genes to their offspring, who in turn would have increased survivability, be better able to reproduce and pas the TAS2R genes to their offspring. Organisms possessing the TAS2R genes have a higher fitness than organisms that do not posses this gene family. Thus, the TAS2R gene family would have been selected for via natural selection and became the ability to taste bitter foods would have become dominant in the population.

This is especially true in the case of the thyroid-inhibiting toxin, PTC. PTC is known to decrease thyroid hormone, which regulates metabolic function. PTC can also lead to liver damage and a host of other medical problems that would eventually lead to death. Being able to taste the PTC toxin would have allowed our ancestors to to avoid toxic foods that if ingested would ultimately lead to their death. Because of this, the ability to taste the PTC toxin would be passed on to the next generation and contribute to the increased fitness of the following generation. In this way, the bitter taste genes would become selected for and would become prevalent in the population.

How the Evolution of Bitter Taste Affects Me Today

Although variation in taste facilitated the evolution of primates and other animals, in modern human society it can be detrimental. With the advent of agriculture, there is less need for tasting of bitter food. Highly nutritious vegetables are known to activate the bitter taste receptors. Instead of doing their intended evolutionary job of protecting from toxic materials, the bitter taste receptors are preventing some people from getting an adequate daily amount of nutritious vegetables due to their aversive taste.

Additionally, some individuals have extremely high sensitivity to bitter tastes resulting from higher rates of expression of the TAS2R gene. These individuals are known as “supertasters”.  Supertasters can be found in the highest frequency in parts of Asia, Africa, and South America. This may be because these areas originally possessed a higher concentration of toxic plants and animals in comparison to other areas. In order to compensate for the increase in potential toxins, the individuals living in this area might have benefited more from bitter taste receptors. Today, many supertasters dislike a wide variety of vegetables such as cabbage and soy, and favor sweet items over bitter vegetables. This not only leads to increased chance of obesity and diabetes, but because of the avoidance of vegetables there is increased risk for GI diseases such as colon cancer. Not all side effects are bad though. Supertasters have a higher dislike for alcohol, carbonated beverages, and smoking. Avoidance of these items is actually quite beneficial in boosting heath.

Next time you don’t feel like eating your vegetables, you can blame it on evolution!

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More Reading…

Campbell, M. C., P. A. S. Breslin, A. Ranciaro, S. A. Tishkoff, D. Drayna, D. Zinshteyn, G. Lema, T. Nyambo, J.-M. Bodo, S. Omar, J. Hirbo, and A. Froment. “Evolution of Functionally Diverse Alleles Associated with PTC Bitter Taste Sensitivity in Africa.” Molecular Biology and Evolution 29.4 (2012): 1141-1153.

Wooding, Stephen. “Evolution: A Study in Bad Taste?.” Current Biology 15.19 (2005): R805-R807.

Evolution in Influenza

Contributed by Runako Aranha-Minnis

Evolution is not only limited to the organisms we are able to see with the naked eye. Viruses like influenza are able to evolve, and this can be very dangerous to human populations. Though it is true that influenza is not the danger that it once was, it still can not be ignored. Viral resistance to treatment can lead to many deaths globally, especially during flu seasons. During these times, doctors usually see a rise in cases of viruses resistant to the treatments available at the time. One type of resistance that influenza can develop is Oseltamivir resistance. Oseltamivir is an important antiviral defense against the flu. It is found in drugs like Tamiflu, and can be rendered ineffective if resistance is developed.

Influenza and its neuraminidase

The DNA change that in the virus that occurs is related to the neuraminidase enzyme activity. The enzyme cleaves salicylic acid moieties that can be bound by the viral hemagglutinin. In essence the enzyme’s job is to help release newly formed viral particles. Imagine the enzyme as little Pac-Men just going about and eating the connections of new virus particles to let them spread. Oseltamivir works by inhibiting the activity of the neuraminidase enzyme. This limits the infectiousness of the virus.

Resistance requires changes in the DNA of the virus. Mutations, changes in the DNA, can change genes, often leading to changes in the organism. For Oseltamivir resistance, a point mutation, the change of a single base of DNA, is all that is necessary. A change in the genes leads to a change in the amino acids produced. This change in the amino acids is just one amino acid at the 274th spot in the chain leads to a change in the activity of the virus. This line of reasoning is why the mutation is called H274Y.

The H274Y mutation that gives influenza resistance usually does not spread through the population.  In early clinical tests, the mutation meant the virus was unaffected by oseltamivir, but had associated decreased viral fitness. So even though viruses with resistance would be selected for, their lower chance of survivability because of the mutation meant it did not matter. The influenza virus is able to evolve with Oseltamivir only when an associated mutation occurs. These associated mutations that allow oseltamivir resistance to keep going are permissive mutations. More recently, permissive mutations have arisen that allow influenza to be resistant to Oseltamivir without losing any fitness. Imagine a population of influenza like a game of “Where is Waldo?”:

No permissive mutations. In the absence of permissive mutations, all viruses, including Waldo, die. 

With permissive mutations. If Waldo has a permissive mutation, he survives to reproduce and the whole populations becomes Waldos because all other viruses died. 

Waldo in the first cartoon has H274Y with no permissive mutations. Without permissive mutations, there is no evolution under treatment. After treatment, the viruses are killed. There are no viruses left so the picture goes black. In the second cartoon, With permissive mutations, there is evolution for Waldo and a new viral population arises. This population only has Waldo because only Waldo has the H274Y mutation that conferred resistance.

For Further Reading:

Jesse D. Bloom, Lizhi Ian Gong, David Baltimore. 2010. Permissive Secondary Mutations Enable the Evolution of Influenza Oseltamivir Resistance Science. 328: 1272-1275

Nicholas Renzette, Daniel R. Caffrey, Konstantin B. Zeldovich, Ping Liu, Glen R. Gallagher, Daniel Aiello, Alyssa J. Porter, Evelyn A. Kurt-Jones, Daniel N. Bolon, Yu-Ping Poh, Jeffrey D. Jensen, Celia A. Schiffer, Timothy F. Kowalik, Robert W. Finberg, Jennifer P. Wang. 2013. Evolution of the Influenza A Virus Genome during Development of Oseltamivir Resistance In Vitro 88: 272-281

The Sad History of HIV and its Persistence against Drug Therapy

Contributed by Oliver Ting, Jackson Fritz and Milan Patel

According to a report from the World Health Organization, human immunodeficiency virus (HIV) infected about 2.7 million new people in 2010 alone. Broken down, HIV destroys the immune system in humans, allowing opportunistic diseases to come in and kill the patient. HIV spreads through bodily fluid from person to person. Once inside a patient, HIV targets certain cells within the immune system called T-cells. HIV forces these cells to create new copies of the virus and destroys the T-cells in the process. As the virus grows exponentially, the immune system loses its ability to fight other diseases, leading to acquired immune deficiency virus (AIDS).

HIV cannot be cured. The main problem in creating a drug that treats HIV is that the virus is constantly changing. HIV is a retrovirus, meaning it uses RNA and then converts that into DNA when it infects cells. Retroviruses use an enzyme called reverse transcriptase to do this. However, unlike DNA enzymes, this enzyme cannot proofread itself, allowing more mutations (changes in the genetic code) to occur. This causes the virus to produce a base mismatch roughly every 10, 000–30, 000 bases during the replication. This differs significantly from regular viruses that typically have a range of one base mismatch per one million to one billion base pairs. When these base mutations occur in specific regions of the HIV DNA, new types or subtypes of the virus can be created. HIV builds up drug resistance because a drug that was effective for a previous variation of HIV may not be effective against a new variant of the virus. In addition, the virus builds cross-resistance, and becomes resistant to multiple types of HIV drugs within the same class. This further limits the number of drugs that can be used to treat the virus.

HIV is a prime example of evolution in action. HIV’s high rate of DNA mutation creates many variants. When HIV is selected against through antiviral drugs, certain variants survive that are resistant to the drug. These drug-resistant strains of HIV survive to reproduce and can be transmitted to other individuals. This constantly changing HIV population produces a substantial obstacle in trying to treat and eradicate the virus. Continued research is required to combat this evolving virus and improve the quality of life of those affected by HIV and AIDS.

Inspired by Radiolab “Patient Zero”, a fascinating tale about how HIV began, where it came from, and who “Patient 0” may have been. The podcast further reinforces how the virus has been able to combat so many challenges to its existence as well as it has.

Further Reading:

Bao, Yi, et al. “Characteristics Of HIV-1 Natural Drug Resistance-Associated Mutations In Former Paid Blood Donors In Henan Province, China.” Plos ONE 9.2 (2014): 1-9.

Bennett, Diane E . et al. “Drug Resistance Mutations for Surveillance of Transmitted HIV-1 Drug-Resistance: 2009 Update.” Ed. Douglas F. Nixon. PLoS ONE 4.3 (2009): E4724.

Sanjuan, R. et al. “Viral Mutation Rates.” Journal of Virology 84.19 (2010): 9733-748.

Shilts, Randy. And the Band Played On: Politics, People, and the AIDS Epidemic. New York: St. Martin’s, 1987.

A Jurassic Park for Real?

Contributed by Tianai Sun and Weili Qu

The mysterious dinosaurs in movies or museums must have amazed you. But have you ever thought about keeping a real pet dinosaur? Good news: it could happen! One of the major misconceptions about evolution is that since evolution occurs slowly, humans cannot influence it. However, modern genetic tools enable humans to accelerate, decelerate, or redirect evolution. To aid the study of evolution, some scientists long to study living dinosaurs. Unfortunately, they went extinct 66 million years ago. To bring back dinosaurs would require abundant dinosaur DNA, which is rare, and more advanced genetic tools than are currently available. Lacking the crucial raw materials, is it possible that we can transform current animals into dinosaurs? Believe it or not, scientists may answer, “chickens!”

It is hard to imagine the transition from chicken to dinosaur, for they are drastically different in both size and appearance. However, a decade ago, Dr. Vargas from Universidad de Chile and his colleagues found that chicken embryos follow the same pattern of digit development as dinosaurs, even though they differ morphologically. This provides strong evidence that dinosaurs are authentic ancestors of chickens. As a result, chickens are an ideal model to be modified into dinosaurs.

Although chickens are closely related to dinosaurs, their major differences, including the “beak” shape and tail length, still induce difficulties in the process of transformation. How exactly could scientists solve these issues?

Chickens and birds have beaks with vestigial snouts, while alligators possess well developed snouts on their upper jaw. They, however, share similar developmental processes. Recently, by manipulating chicken embryos, Dr. Arhat Abzhanov successfully generated a modified chicken whose beak was similar to an alligator’s snout. Given that the snouts of alligators are morphologically similar to that of dinosaurs, this groundbreaking achievement brings us one step closer. Similarly, scientists are endeavoring to identify genes that control tail development in order to extend the tail of chickens, mimicking the tail of a dinosaur. If this goal is achieved, the creation of “chickenosaurus” as well as the realization of the Jurassic Park could be within reach in the future. Regardless of whether this happens, we will gain fundamental insights into how developmental patterns evolve.

More broadly, advanced scientific developments provide humans with the ability to explore the world. Genetic tools are widely used in biological research and are surprisingly effective in bringing about novel knowledge. While evolution often occurs slowly, the idea that humans cannot impact evolution due to its slow rate is incorrect, exemplified by the attempt to recreate features of extinct dinosaurs through genetic approaches. So, don’t be disappointed if scientists are unable to bring the amazing dinosaurs back to you, for even simply recreating specific phenotypes of dinosaurs in model systems enlightens our understanding of dinosaur evolution.

To see how a chicken could be transformed to have a dinosaur-like snout, claw and tail, check out the video below:

For More Information…

1.Ted Talk: Jack Horner: Building a dinosaur from a chicken

2.Horner, J. R. 2001. Dinosaurs under the big sky (p. 195). Missoula: Mountain Press Publishing Company.

3.Grossi, B., Iriarte-Díaz, J., Larach, O., Canals, M., & Vásquez, R. A. 2014. Walking Like Dinosaurs: Chickens with Artificial Tails Provide Clues about Non-Avian Theropod Locomotion. PloS ONE, 9(2), e88458.

4.Carrano, M.T., Biewener, A.A. 1999. Experimental Alteration of Limb Posture in the Chicken (Gallus gallus) and Its Bearing on the Use of Birds as Analogs for Dinosaur Locomotion. JOURNAL OF MORPHOLOGY, 240:237–249.

5.Vargas, A.O., Fallon, J.F. 2005. Birds Have Dinosaur Wings: The Molecular Evidence. JOURNAL OF EXPERIMENTAL ZOOLOGY (MOL DEV EVOL) 304B:86–90.

6.Carrano, M. T. 1998. Locomotion in non-avian dinosaurs: integrating data from hindlimb kinematics, in vivo strains, and bone morphology. Paleobiology Vol.24, No. 4, pp. 450-469.

7.Padian, K., Horner, J. R. 2011. The evolution of ‘bizarre structures’ in dinosaurs: biomechanics, sexual selection, social selection or species recognition?. Journal of Zoology, 283: 3–17.

Got Lactase?

Contributed by Seth Appiah-Opoku, Judy Chen, and Steven Sun

Do you know anybody who is lactose intolerant? Today, about one-third of people in the world are unable to digest lactose, milk sugar. It is likely that before the agricultural revolution, most people were lactose intolerant. After populations began to raise cattle rather than search for their food on a daily basis, people had more access to milk, a luxury that was previously only consumed when they were infants. On the chance that food became rare, individuals who were able to digest lactose—lactose persistent individuals—were more likely to survive because they could consume milk instead. Because they were more likely to survive, these people were also more likely to have children, passing on their ability to digest lactose, and therefore increasing the presence of this ability in the population.

According to current research on the topic, the genetic mutation that causes lactose persistence appeared first in the Arabian Peninsula and Middle East around 6,000 to 2,000 years ago before spreading to northern Africa. Around that similar time, the domestication of cattle was already established in northern Africa. Within Africa, cattle domestication further spread from the Sahara to Sudan and northern Kenya about 4,500 years ago. Then, about 3,300 years ago, cattle domestication continued to spread into southern Kenya and northern Tanzania. Following a similar time scheme, the Arab expansion led to an increased mixing of different populations, and the lactose persistence gene was introduced into eastern Africa within the last 1,400 years. Ultimately, lactose persistence spread to southern Africa within the last 1,000 years.

Further research is being conducted; however there is strong evidence that because lactose persistence and the domestication of cattle arose around the same time in similar areas, it is likely that the development of lactose persistence was a result of cattle domestication.

To read the paper behind this information, check out:

Ranciaro, A., Campbell, M. C., Hirbo, J. B., Ko, W., Froment, A., Anagnostou, P., … Tishkoff, S. A. (2013). Genetic origins of lactase persistence and the spread of pastoralism in africa. American Journal of Human Genetics, 94, 1-15.