Sunday, February 19, 2017

The great asparagus experiment: investigating the genetic basis for asparagus anosmia

After the great success of the cilantro experiment, we decided to undertake a similar approach with asparagus. As you probably know, some people find that asparagus makes their urine smell funny, while others experience no effect. In fact, observations on the effect of asparagus have been made as early as the 1700s. Ben Franklin included some negative comments about asparagus ("A few Stems of Asparagus eaten, shall give our Urine a disagreable Odour") in his essay on flatulence (I think my son's budding interest in Franklin will increase greatly knowing that Ben was equally interested in lightning and farts!)

In contrast to the cilantro experiment, where I dislike the taste of the test food, I have no idea what the big deal is with asparagus, but my husband tells me of the foul smell that is the result of enjoying this verdant spring vegetable. Depending on the study, 33-60% of people cannot detect the smell. In our experiment, we all enjoyed a side of asparagus that was lightly pan seared with olive oil. Our son was not too excited by the taste of the vegetable, but he ate it for the sake of science. Frankly, I think he was curious what the outcome would be. After our next bladder evacuations, we compared notes on the smell. It seems my son has inherited his father's perception of asparagus smell. Unfortunately for us, this fun experiment did not encourage our boy to eat more asparagus. Rather, he can now use the smell as an excuse to avoid it.

Next came the moment in the experiment to explain what happened and why. The first question is what it is about asparagus that makes urine smell different. Luckily, that one is firmly based in chemistry, so it is relatively straightforward to answer. The odor is the result of the metabolism of a chemical unique to asparagus: asparagusic acid. The infographic below from Compound Interest on the Chemistry of Asparagus includes the specifics on the chemical structures if you are curious. Asparagusic acid breaks down into four other sulfur-containing compounds, which happen to be volatile, evaporating quite readily and giving up their pungent odors in the process. Methanethiol and dimethyl sulfide are thought to be the culprits for the smell; this was determined by giving people purified forms of either compound, which can induce the smell without eating asparagus. It is thought that asparagusic acid helps asparagus keep pests away in the wild; the compound can prevent the growth of fungi as well as parasitic nematodes; consistent with this, the concentration of asparagusic acid is highest in the emerging shoots and other parts of the plant that are likely to be infected.

The second question is why only some people experience the smell while others don't. The answer to this question is based in genetics and sense perception, so it is a bit more complicated. As with so many phenotypes, there is not one simple genetic explanation. There are two main physiological issues here: the metabolism of the asparagus and the perception of the smell of those metabolic byproducts. For some time, scientists thought that everyone was an excreter (meaning they could produce the smell in their urine), but that some people could not perceive the smell (the scientific term is anosmia). As more scientists started to ask people about their experience with asparagus, the story became murkier. There is variation in how people perceive the smell (from strong to mild) and there is also a small population of people that that do not metabolize asparagus the same way. 

There have been a number of papers looking at the genetic connection between anosmia and asparagus. A 2010 PLOS Genetics paper published by the personal genomics service 23andme seems to be the first paper linking asparagus anosmia to a particular genetic variation. The paper showed that several single nucleotide polymorphisms (SNPs) occurring near genes encoding for odor receptors were correlated with asparagusic acid anosmia. The most significant association was seen in a gene encoding olfactory receptor 2 (OR2M7), where the variation acted in a dominant fashion to decrease the likelihood of anosmia.

genome-wide association study (GWAS) published in the journal BMJ in 2016 looked at a group of nearly 7000 Europeans. Their results suggest that a majority of this group (60%) had anosmia, with it being slightly more common in women than in men. Consistent with the results from 23andme, they found several SNPs in the olfactory receptor 2 gene. Thus, there is good evidence for the genetic basis for asparagus anosmia.What is still unknown is what SNPs (if any) are associated with the inability to excrete aspargusic acid. In addition, it is unclear if the ability to detect this smell has any evolutionary basis or if it is just a random mutation.

These experiments taught me a lot about the science of food and taste perception. There are lots of opportunities to experiments with food in the future, While most of my previous experiments with food involve baking, there are lots of opportunities to experiment with food in the future. For example, this post from Discover Blogs talks about the large variety in how humans perceive tastes and the opportunity for citizen science to unravel that. I will be sure to post an update about our next foray into human genetics and food.