Of microbes and men: Testing the neutral theory with the human microbiome

There is no doubt that one of the hottest current topics in microbiology revolves around the human microbiome. There have been a suite of recent studies we’ve highlighted, on organisms ranging from bees and mice, to humans. A quick google scholar search identifies over 12,000 studies on the human microbiome from 2016 alone.

Figure 2. Human Microbiome Project Consortium, 2012


There are various efforts to characterize the human microbiome, such as the one run by the NIH, established in 2008, with various ambitious goals including determining how disease affects our microbial fauna and the development of a microbial reference genome data set. They also published a nice summary back in the day on the structure and diversity of a healthy human microbiome.

Figure 4. Human Microbiome Project Consortium, 2012.


Although, interestingly enough – it’s not just scientific journals that are focusing on these bacterial communities. I finally ordered my copy of I Contain Multitudes, by Ed Yong (which you’ve likely either read, plan to read, or heard about), that discusses how our microbiome is a big part of who we are.
Microbiomes associated with select organisms represent model systems that will allow us to ultimately unravel the complex interactions among microbes in the environment. If you’re interested in keeping up with the Joneses concerning microbiome studies, you might want to check out Elisabeth Bik’s blog on the topic. It has proven to be (quite understandably) interesting and difficult to figure out how microbes interact in their natural habitats, understanding microbial community ecology is important, but definitely not easy.
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How Molecular Ecologists Work: Sarah Hird on resenting Adobe, letting yourself off the hook, and starting with the hard work

Hird_coffee

Welcome to the next installment of How Molecular Ecologists Work! This entry is from Dr. Sarah Hird, postdoc at the University of California, Davis Genome Center and (new!) assistant professor at the University of Connecticut come this fall. Sarah has worked on phylogeography, microbial genomics, and the development of bioinformatics tools.

Sarah was the winner of the 2014 best presentation at the Festival of Bad Ad Hoc Hypotheses (BAHFest), proving that you can be a productive scientist and a funny person at the same time.

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Microbes can rapidly evolve host-protective traits

One of the coolest studies I’ve come across so far this year is the fascinating story about microbe-mediated protection in worms by Kayla King et al.
The bacterium Enterococcus faecalis normally causes mild disease in worms (Caenorhabditis elegans). After a week with this bacterial infection, fewer than one in a hundred worms dies. In contrast, Staphylococcus aureus is a highly dangerous bacteria, killing over half of the worms within a day. Interestingly, when you mix the two pathogenic bacteria together, E. faecalis protects the worms from the more virulent competitor, reducing the worms’ mortality rate from 52% to only 18%.
King et al. wanted to investigate if it was possible to select for this mutualistic defensive trait exhibited by E. faecalis, so they continually harvested the bacterium from the worms for 15 worm-generations. The worms and the virulent S. aureus, however, were derived every time from the same genetically identical stock to make sure only E. faecalis could evolve.
King et al.
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Understanding the pieces of all those meeces: characterizing mice gut microbiota

tom and jerry

Image from Google image commons


In an age where a tremendous amount of data is generated, this week has seen some moves towards providing open access to extensive data sets. These attempts have been in the realm of chemistry as well as microbiology, where in a recent paper by Lagkouvardos and colleagues, access was provided to a set of isolates and their respective genomes, characterizing the microbial diversity of mice intestines.
It’s evident that human microbiomes are linked to both physical and mental health, and it’s also essential to understand how gut fauna might also affect mice. Since mice models are used extensively to predict how drugs might impact humans, it’s only logical we characterize the diversity and overlap humans share with the microbiomes of our furry little friends.
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Phenotypes in Comparative Phylogeography

Earlier this week, The Molecular Ecologist contributor Bryan McLean posted about the current state of comparative phylogeography (Riddle 2016). He listed several exciting directions that comparative phylogeography is heading, including more research that includes trait data.
As a followup to Bryan’s post, I looked into a few ways that recent studies are bringing together phenotype and comparative phylogeography, and what the field might gain from it. 
The problem

For most comparative phylogeographic studies, concordance is the null hypothesis. By including trait data, we can generate more refined phylogeographic hypotheses. Figure from Papadopoulou and Knowles 2016.

Concordance is the null hypothesis in most comparative phylogeographic studies. By including trait data, we can generate more refined phylogeographic hypotheses. Figure from Papadopoulou and Knowles 2016.


The standard approach to comparative phylogeography assumes concordance (i.e., that a biogeographic barrier will cause the same spatial and temporal divergence patterns in multiple species). Discordance is generally regarded as uninteresting or stochastic (Papadoloudou and Knowles 2016).
But disregarding discordance may not always be beneficial or appropriate. A biogeographic barrier may influence multiple species, but to varying degrees depending on phenotype. Phenotypes related to locomotion, physiological tolerance, and body size, for example, can either promote or constrain population divergence (Zamudio et al. 2016).
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How Molecular Ecologists Work: David Toews on the joy of making figures, reading in the field, and the magic track pad

Welcome to the next installment of How Molecular Ecologists Work! This entry is from Dr. David Toews, Banting Postdoctoral Researcher at Cornell University. David’s uses genomic data in combination with phenotypic, geographic, and behavioral data to ask questions about the evolution of birds.

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A Comparative View of Comparative Phylogeography

A recent issue of PNAS includes papers from a Sackler Colloquium on comparative phylogeography. As stated by the organizers, a major purpose of that gathering “was to bring together leading scientists to address the current state of phylogeography as the discipline enters its fourth decade” (Avise et al. 2016).

Four decades?!?

Time flies when the collective goal is identifying evolutionary processes that generated the spatial genetic patterns of (ideally) every species on Earth. Even comparative phylogeography, which synthesizes across single-species phylogeographies to understand how evolution and environment interact at the community scale, is a ripe old age of 30.

Comparative phylogeography occupies an intermediate position between landscape-level investigations and evolutionary biogeographic studies at higher taxonomic levels.

Comparative phylogeography occupies an intermediate position between landscape-level investigations and evolutionary biogeographic studies at higher taxonomic levels. (Figure 7 from Riddle (2016)).

As a contribution to that PNAS issue, Brett Riddle writes a timely review of the field of comparative phylogeography (“CP”). His review is focused specifically on continental systems, and it uses a database of 455 studies to assess trends and biases in the field to date. I talk about a few highlights below (hopefully inspiring you to read the paper in full).

Of course, dataset size and scope exhibit major trends in CP over the past 15 years. Not unexpectedly, Riddle finds that the size and genomic scope of phylogeographic datasets has increased across this period. However, it is also clear that few CP studies are using nuclear data to the exclusion of organelle genomes. This is because:

…organelle DNA, particularly mitochondrial DNA in animals, still likely delivers a very strong and heuristically valuable first approximation of geographic genetic architecture. (Riddle 2016)

Riddle (rightly) points out that organellar DNA is heuristically valuable as well; it can be used to generate hypotheses of past or present secondary contact and introgression. Those hypotheses can then be robustly tested with larger, potentially genomic-scale datasets.

Another trend is in the geographic focus of CP studies. We should celebrate the notable increases in the proportion of studies focused on the Southern Hemisphere. Riddle also recovers a near-global distribution of CP ‘hotspots’ – regions where studies are proliferating and might shed a particularly bright light on community-level evolution.

Yet, there are conspicuous directions in which CP could profitably expand – but hasn’t. For example, incorporation of biological or ecological relationships into CP studies is rare. That is an important direction to pursue because phylogeographic patterns of codistributed taxa are more richly compared and contrasted in light of basic natural history data. Another gap is the focus on trait evolution. If biological or ecological factors are indeed suspected to be driving evolution below the species level, then quantifying traits relevant to these factors may help to explain phylogeographic patterns. Finally, a few regions continue to be underrepresented in CP in general (Middle East, India, Tibetan Plateau).

Each of Riddle’s proposed ways forward for CP is sound; an overarching theme is that there is much to gain by interfacing with other disciplines. Yes, genomic-scale data will continue to help resolve fine-scale phylogeographic patterns and reveal cryptic instances of past contact. But equally auspicious for CP will be advances outside the field of molecular evolution: improved distribution modeling, more precise and higher-resolution trait data, new fossil discoveries, and continued refinement of existing geological and climatic hypotheses.

Cited:

Avise, J. C., Bowen, B. W., and Ayala, F. J.. 2016. In the light of evolution X: Comparative phylogeography. Proceedings of the National Academy of Sciences 113: 7957-7961.

Riddle, B. R. 2016. Comparative phylogeography clarifies the complexity and problems of continental distribution that drove AR Wallace to favor islands. Proceedings of the National Academy of Sciences 113: 7970-7977.

Posted in Coevolution, community, comparative phylogeography, phylogeography, population genetics | 1 Comment

On (mis)interpreting STRUCTURE/ADMIXTURE results

STRUCTURE, ADMIXTURE and other similar software are among the most cited programs in modern population genomics. They are algorithms that estimate allele frequencies and admixture proportions under the premise that sampled genotypes are derived from one of “K” ancestral populations, and have been widely used to (1) detect and estimate population structure, (2) quantify ancestral admixture, and (3) build the basis for complex evolutionary hypotheses about population evolution.

However, interpreting the results of these methods has often been contentious (see Gilbert et al. 2012, Lawson et al. 2012), mostly around interpretation of “K” ancestral populations. Additionally, alternate evolutionary scenarios can also produce similar observable patterns using STRUCTURE/ADMIXTURE. For e.g. three alternate scenarios – one of recent admixture, one of admixture with unsampled/unobservable “ghost” populations, and a third with a recent bottleneck are described in Falush et al. 2016 (also see the interesting Twitter conversations here and here).

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A tale of mammoths and a disappearing lake

A Herd of Mammoths. Source: WikimediaCommons/Kira Sokolovskaia

A Herd of Mammoths. Source: WikimediaCommons/Kira Sokolovskaia


A wonderful study revealed a sad story of the St. Paul Island population of woolly mammoths. Using a creative and diverse set of analytical approaches, scientists identified freshwater shortage as the likely cause of their extinction.
A cross-disciplinary collaboration of scientists from The Pennsylvania State University, University of Alaska, and University of California, Santa Cruz, yielded five different types of evidence suggesting that the last mammoth disappeared from St. Paul Island at the same time as the main (or only) freshwater source evaporated.

What goes around, comes around – even extinction

St. Paul Island is a rather small island of 110 km2. It was originally part of the Bering Land Bridge, but became isolated due to rising sea levels at the end of the Ice Age. A population of mammoths was trapped on the island, which strangely saved them from extinction.
When the St. Paul mammoths finally went extinct 5,600 years ago, there was only one other population of mammoths – their distant relatives also struggling for survival about 1,500 kilometers from there, on the much larger but mountainous Wrangel Island.
While we still don’t know what exactly happened to the very last mammoths on Wrangel Island, climate is probably to blame for the St. Paul extinction. The rising sea “consumed” coastal lakes and the increasingly arid conditions between 8,000 and 5,300 years ago led to freshwater shortage. Continue reading

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How Molecular Ecologists Work: Aaron Shafer on the perfect sentence, making phone calls, and German hip-hop

Aaron_goat_hair_resize

Welcome to the next installment of the How Molecular Ecologists Work series! For this entry, we have Dr. Aaron Shafer, who is currently transitioning from a postdoc position at Uppsala University to an assistant professor position at Trent University. Aaron uses molecular tools to understand the history and future of wild mammal populations (mountain goats, deer, even walrus!). His approach has produced multiple projects with both conservation applications and insights into the evolution of wildlife populations.

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