Sunday, July 31, 2016

Welcome to the Microbiome: the fascinating hidden world of microbes in, on, and around us

In case you haven't heard, you are hosting a very large and diverse population of microbes   from the top of your head to the soles of your feet and everything in between. The term used for these collections of microbes is microbiome or microbiota. This is a very hot topic of scientific research aiming to understand how the microbes around us and within us may be affecting our physiology.

We recently visited the American Museum of Natural History. I was disappointed that we forgot to purchase tickets for The Secret World Inside You exhibit. Luckily, I came across a review on CrossTalk for the new book by Susan Perkins (the curator of the exhibit) and Rob DeSalle. Welcome to the Microbiome: Getting to Know the Trillions of Bacteria and Other Microbes In, On, and Around You turned out to be a good substitute.

The book is very well written and easy to read. It is an excellent introduction to the microbiome for even the non-science type. The book covers the major topics
starting with the basics of defining life and classifying bacteria as well as the concept of the microbiome. The book describes some of the latest research that investigates the microbes that live around us and inside us and how these collections of organisms are linked with human health and disease. Finally, they discuss what a healthy microbiome is and whether or not this is even a meaningful idea.

Description of metagenomic sequencing from Teach the Microbiome
The microbiome research that makes headlines typically focuses on the microbiomes of everyday places and things (e.g., subways, bathrooms, kitchens) or the human microbiome and how these microbes can be linked to disease. One critical point the authors highlight is how the revolution in genome sequencing and the advent of next-generation sequencing techniques has made these types of studies possible. The scale of microbiome studies can be astounding. Researchers collect hundreds of samples and these samples can contain hundreds of different species of microbes. Using advance genome sequencing techniques, researchers can sequence and analyze these complex samples and detect even small differences in populations between the samples.

I wanted to discuss a few of the studies that the authors highlighted in their section on the microbes on and around us. My favorite was published in 2013 by Meadow et al. (coverage in outlets like Wired and The New Yorker), where the researchers examined the skin microbiomes of the players involved in a roller derby tournament. By comparing the skin microbes present on  players before and after two games of this high-contact sport, they learned that the different teams started with distinct microbe populations with some variety based on the geography of the team (i.e., the team from Boston had similar microbes to the team from New York, but not San Francisco). After a jam, the teams had swapped skin microbes. The lead author on the study was a former derby skater, who thought that the sport offered a unique chance to study how microbes spread through human contact. 

Another fascinating and ambitious research endeavor is the PathoMap project , which aims to categorize the microbiome in a variety of human-made environments in New York City. They started in the subway system, where they took samples from all 468 stations in NYC. They sampled ticket kiosks, turnstiles, benches, trashcans, and at places within the train itself. The first results from this study were published in Cell Systems. The results revealed an abundance of human skin bacteria as well as a rather disturbing (but frankly not surprising) number of fecal bacteria. A more recently published study examined the microbiome of the Boston subway system (original research and coverage), which showed little variation in the different subway lines even though they serve different populations. In addition, most of the microbes found were exactly what you would expect
the bugs that typically inhabit our skin, gut, and mouths; occasionally samples from seats contained microbes usually found in the human vagina. The researchers plan to expand their study to investigate the microbial changes during cold and flu season. In addition to helping us to understand how microbes spread, these types of studies can have important implications for designing human environments to help prevent the spread of disease.
Descriptions of sampling methods in Hsu et al., 2016 (

The study of microbiota is still in its infancy, so it is an exciting time to follow the research here. If you want to learn more about the microbiome, the AMNH exhibit is probably a great place to start, but if you can't get to NYC, Welcome to the Microbiome is a great alternative.

Wednesday, July 13, 2016

The trouble with A Troublesome Inheritance by Nicholas Wade

I started to worry about my choice to read A Troublesome Inheritance by Nicholas Wade as soon as I began the preface, which detailed the controversies surrounding the book. Despite my hesitation, I soldiered on.

Wade sets out to challenge the idea that race is solely a social construct, and he aims to show that there are genetic differences between different races (geographical groups or clines) of humans. The author argues that humans are still evolving and have done so since the time humans started to separate geographically. I think most biologists would agree with this premise; a recent story in Science confirms that humans are still evolving in an observable way. If this idea is true, then there should be genetic differences between the human populations that resulted from this geographical separation. What makes this topic "troublesome", of course, is that the history of scientists attempting to understand race in a biological context has been fraught with prejudice, to say the least. Wade acknowledges these concerns and says that he thinks that any genetic differences between races cannot and should not be the basis for a judgment about the worth of one group over another. However, he then proceeds to speculate on why European populations have fared so much better in economics and history than Asian and African populations; he concludes that Europeans simply have higher IQs and stronger work ethics. These conclusion led many scientists to criticize his work as scientifically inaccurate (some of the best examples are herehere, and here). In a style typical of James Watson, Wade essentially dismissed his critics as PC police.

I expected the book to detail what exact genes are found to differ between human populations. I figured these genes would be interesting, but biologically unimportant. Unfortunately, Wade gives only a few specific examples, which I will discuss here with more detail. He starts with the genes MC1R and SLC24A5; variations in these genes are linked to changes in skin and hair color and affect the ability to absorb vitamin D from the sun. I discussed MC1R extensively in my post about red hair; MC1R essentially initiates a cascade of cellular events that turns on the production of pigment synthesizing genes. Likewise, SLC24A5 also affects melanin pigment production (Science 2005). Single nucleotide polymorphisms (SNPs), such as the A111T allele, are found in 98-100% of the SLC24A5 genes sequenced in European populations.

Graphical Abstract from Kamberov et al., 2012 (Cell)
Another gene that shows population-based differences is EDAR; SNPs in EDAR in East Asian populations are linked with thicker hair and changes in tooth structure. A recent study in Cell showed that mice with the East Asian EDAR variant (V370A) had thicker hair as well as smaller mammary glands and fewer sweat glands. It is unclear how this variant arose; some scientists speculate that smaller breasts were chosen via sexual selection, while others argue that the decrease in sweat glands would have been an advantage in the cold environment of Asia when the variant appeared (additional coverage of this cool paper in the NY Times).

A surprising phenotypic difference in East Asian populations is the presence of dry ear wax, which is caused by variants in the ABCC11 gene, which encodes a protein transporter that helps the cell transport various substances across cellular membranes. SNPs in ABCC11 are also linked with decreased body odor (find out more on the Discover Magazine Gene Expression blog). In this case, scientists argue that changes in ABCC11 were caused either by the advantage of lacking body odor in sexual selection or the advantage of decreased body odor in a cold environment; the ear wax phenotype was merely a hitchhiker.

In the end, I was disappointed that the book discussed so few genetic variants and did not detail these genes very well. There is a definitely an interesting topic here; unfortunately, A Troublesome Inheritance is not the place to read about it. Perhaps if Wade (a science writer for the New York Times and Nature) had enlisted the assistance of a anthropologist or a population geneticist, the book would be more successful.  I have started writing a follow-up post on this topic; in particular, I
want to address these genetic differences in light of advances in genome sequencing and personal genomics.