Saturday, March 29, 2014

We're hiring


Seth Bordenstein ( is seeking a postdoctoral fellow in metagenomics, microbial ecology, or systems biology.  The ideal candidate will pursue innovative research that compliments ongoing work in the lab on evolution, genome-microbiome interactions, and phylosymbiosis. We particularly encourage applications in the following areas:

·      Host-associated microbiomes (including but not limited to 16S rRNA gene sequencing, metagenomics, metatranscriptomics, metabolomics, and bioinformatic analyses using animal, plant or microbial systems)
·      Systems Biology (including but not limited to novel approaches in the genesis and processing of multi-omic data and models to integrate these data)
·      Quantitative and Computational Biology (including but not limited to bioinformatics, comparative functional genomics, and population genetics of large data sets)

We welcome cross-disciplinary approaches to understand how animals develop, function, interact and evolve. All candidates must have demonstrated excellence and creativity in applying next-generation sequence data to quantitative community, evolutionary, or ecological themes.

To apply or ask questions, please send information to Seth Bordenstein ( Please submit a CV and 1-2 page research statement describing your research interests, background and your goals for your career and postdoc. Please also include the names and contact information for at least 3 references. Applications will be reviewed immediately until a suitable candidate is identified.

Monday, March 17, 2014

Is Natural Selection Not the Right Brand for Evolution?

Mutation, Not Natural Selection, Drives Evolution


I just read the above article in Discover (link: March 16, 2014) that captured my curiosity. Famed population geneticist Masatoshi Nei claims that evolutionary biology has overly relied on "natural selection" as the brand name for evolution, and he makes a fair argument. He suggests an alternative - mutation driven evolution - that can seem subtle in comparison to natural selection at first glance, but it is not subtle. Why would biologists revise their heavy use of natural selection in favor of evolution by mutation?
  • First, mutations come before natural selection. Without genetic variation, there can be no change in an organism that is directed by natural selection. Nei states:
Mutation means a change in DNA through, for example, substitution or insertion [of nucleotides]. First you have to have change, and then natural selection may operate or may not operate. I say mutation is the most important, driving force of evolution. Natural selection occurs sometimes, of course, because some types of variations are better than others, but mutation created the different types. Natural selection is secondary.
  • Second, evolution by natural selection ignores that some variation arises by neutral mutations (that have no effect on the organisms' function) and population size crashes can cause those mutations to spread. So why would biology want a universal brand name like Natural Selection that misses the "neutral" side of evolution?
  • Third, it is Nei's opinion that natural selection is a deterministic force that simply replaces the hand of God as that deterministic force. Herein lies something important to consider.
If you say evolution occurs by natural selection, it looks scientific compared with saying God created everything. Now they say natural selection created everything, but they don’t explain how. If it’s science, you have to explain every step. That’s why I was unhappy. Just a replacement of God with natural selection doesn’t change very much. You have to explain how.
Part of the crux of the theory of evolution is that random mutations arise in a manner that is inconsistent with a deterministic hand. Changes are not orchestrated by want of a higher power but by random genetic processes that cause errors in the DNA code. It's equivalent to the randomness of the universe. 

My favorite Nei quote is at the end. It is a message for all students of science:
But any time a scientific theory is treated like dogma, you have to question it. The dogma of natural selection has existed a long time. Most people have not questioned it. Most textbooks still state this is so. Most students are educated with these books. 
You have to question dogma. Use common sense. You have to think for yourself, without preconceptions. That is what’s important in science.

Monday, March 10, 2014

Al Gore on the Microbiome and Darwin

When former Vice President Al Gore preaches the MICROBIOME, it may be time to switch fields as the bubble of exponential growth has officially burst. Sorry folks, but tis true. He does give a shocking and swift shout out to Darwin though. In all seriousness, I applaud the former VP for preaching fairly accurate science. Every drop of science education counts in the U.S.A. 

Saturday, March 8, 2014

President Obama to introduce Fox's 'Cosmos' series on March 9

"We are made of star (microbe) stuff. We are the way for the (micro)COSMOS to know itself." - Carl Sagan (modified)

Tomorrow night, Science comes back to mainstream TV to reclaim its rightful entertainment and knowledge value. Join the journey and share the excitement about the new COSMOS show hosted by Neil Degrasse Tyson - the heir apparent to  Carl Sagan - who is serving the public's appetite for science and wonder. The mission of this TV show and what we all do as scientists are aligned in advancing science education and the beauty of discovery. 

Here is Neil Degrasse Tyson speaking at his usual best on scientific literacy.

Friday, February 7, 2014

Guest Blog Post on Helicobacter pylori: Friend or Foe?

We're not too far into 2014 and we already have a contender for "favorite paper of the year". This treat is the story behind that paper - one that remarkably interconnects phylosymbiosis with human health. 

Kodaman et al, PNAS 2014 

Contributed by Carrie L. Shaffer, PhD
Twitter @CLShafferPhD

Electron micrograph of H. pylori (Source)

Global dissemination of Helicobacter by modern humans

One of the most successful human pathogens in recorded history is Helicobacter pylori, a Gram-negative bacterium that has colonized the gastric niche of modern humans since our migration out of Africa approximately 60,000 years ago.  Since leaving Africa, H. pylori has diversified in parallel with its human host.  Because of the predominantly vertical transmission of H. pylori within family units and the chronic carriage of H. pylori for nearly the entire lifetime of an individual, we have the remarkable ability to trace human migrations by analyzing H. pylori genetic signatures.  Recent evidence suggests that H. pylori has colonized humans for at least 100,000 years, and points to a second exodus out of Africa 52,000 years ago that resulted in generation of a hybrid European lineage of H. pylori strains (Moodley et al.).

Today, H. pylori colonizes the gastric mucosa of at least 3 billion people worldwide. Gastric colonization by H. pylori results in the development of asymptomatic chronic non-atrophic gastritis in all cases.  However, in a small percentage of cases, severe gastric disease can manifest, including emergence of peptic ulcers and gastric adenocarcinoma, which is currently the second leading cause of all cancer-related deaths worldwide. In contrast to the United States, where the prevalence of gastric cancer is low, the incidence of gastric adenocarcinoma varies globally with the highest rates occurring in Japan, China, South America, and Eastern European nations.

Because of its diverse and segregated geographic and ethnic landscape, the South American country of Colombia serves as an ideal natural laboratory for the study of H. pylori-related disease and its association with gastric adenocarcinoma. Separated by only 200 kilometers, the Colombian towns of Tuquerres and Tumaco have sharply contrasting rates of gastric cancer.  Tuquerres, located in the altitude of the Andes Mountains, has one of the highest rates of gastric cancer in the world (approximately 150 cases/100,000 people), whereas the coastal town of Tumaco has a gastric cancer rate of just 6 cases per 100,000 people, despite a nearly universal rate of H. pylori colonization throughout Colombia.  

Health outcomes echoing a continued legacy of European colonization

A rich history of settlement by native Amerindians coupled with both colonization and conquest by Spanish invaders and the introduction of African slave trades led to racial and ethnic segregation within Colombia.  People residing in modern day Tuquerres are mainly of mestizo (Spanish and Amerindian) descent, while the residents of Tumaco are primarily of mulatto (African and Spanish) descent.  These observations led us to the central question of our recently published paper in PNAS (Kodaman et al.): Are the rates of gastric cancer in Colombia governed by human or Helicobacter ancestry? We reasoned that a 25-fold difference in the rate of stomach cancer between the two populations could be attributed to differences in the host genetic composition; differences in host immune responses to chronic infection; phylogeographic origin and/or virulence factors harbored by H. pylori; environmental factors such as diet and smoking status; or a combination thereof. 

Our previous work (de Sablet et al.) demonstrated that European H. pylori ancestry is strongly predictive of increased premalignant lesions and epithelial DNA damage in both Colombian populations, while African H. pylori phylogeographic origin is associated with reduced severity in histologic disease parameters.  These findings are significant because we were able to show that in this region, the genetic ancestry of H. pylori is both a risk factor for development of gastric disease and a determinant of gastric disease severity, irrespective of the presence of the major virulence factors CagA (an oncoprotein present in some strains of H. pylori) and VacA (a secreted toxin present in all strains of H. pylori).  However, this study was constrained to a small subset of our larger cohort, and thus, we wanted to further investigate how Helicobacter phylogeographic origin contributes to development of gastric cancer.

In our follow-up study, we expanded the number of patients analyzed to 242 (122 from Tumaco and 120 from Tuquerres), and focused our efforts on analyzing human ancestry in parallel with the phylogeographic origin of the H. pylori cultured from patient-matched gastric biopsies.  Using Immunochip analysis to genotype nearly 200,000 SNPs in each patient’s blood sample, we determined that human ancestry closely followed expected patterns based on historical events: the people of coastal Tumaco trace the majority of their ancestry to Africa (58%), while the mountain population of Tuquerres are largely of Amerindian (67%) and European (31%) descent. We used multilocus sequence typing (MLST) to determine the matched H. pylori phylogeographic origin from each patient, and classified each isolate into an ancestral haplotype based on analysis of housekeeping gene sequences using STRUCTURE.  Helicobacter phylogeography recapitulated our previous report indicating that the bacteria derived from ancestral European, African, and East Asian (Amerindian) lineages.  The matched human and Helicobacter ancestries were then correlated to histopathology scores from gastric biopsies taken from each patient in order to determine if either human or H. pylori genetic ancestry was associated with disease severity.

The answer surprised us: we found that perturbation of human-Helicobacter phylosymbiosis can shift a benign infection to a potentially catastrophic relationship that results in disease progression to gastric cancer.  Rather than either the human or the bacterial ancestry acting alone, the contribution of bacterial-host genetic interplay was found to be the most significant factor for predicting disease outcome.  This result was even more captivating when we analyzed the influence of the major carcinogenic virulence factor CagA on the progression of advanced gastric disease within this cohort – human-microbe incompatibility had a greater effect on the risk for developing severe disease than the bona fide Helicobacter oncoprotein.  We went on to show that disruption of human-Helicobacter phylosymbiosis accounts almost entirely for the differences we observe in stomach cancer risk between Tumaco and Tuquerres.  To our knowledge, this study was the first report of matched genetic analysis of the host and pathogen with subsequent correlation of human-microbe phylosymbiosis to clinical outcome.

Reflections of a distant past

So what do our results mean? One theory is that invasion of Colombia by the Spanish conquistadors introduced ancestral European H. pylori to the Amerindian populations, and these bacteria replaced the East Asian H. pylori strains naturally harbored by the Tuquerres population.  It is thought that H. pylori of European ancestral origin may be more virulent than some other lineages, including H. pylori of ancestral African and Amerindian haplogroups. Since many people are often co-infected by multiple H. pylori strains, it is reasonable to hypothesize that H. pylori of European lineage could have outcompeted strains of Amerindian lineage in native Colombians. Alternatively, co-infection with multiple H. pylori strains and the natural competence of the bacterium leads to a propensity of H. pylori to uptake DNA for recombination, resulting in generation of new strains that are entirely unique at the DNA level. Another possibility is that differences in virulence factors between H. pylori phylogenetic lineages could provide a competitive advantage during co-infection. In fact, analysis of the cag pathogenicity island (which encodes components of a molecular machine used by H. pylori to inject CagA into gastric epithelial cells) in several Amerindian H. pylori isolates revealed numerous changes, including gene rearrangements, indels of approximately 11.2 kb (one quarter the size of the entire pathogenicity island), and gene inversions (Olbermann et al.).  Despite these dramatic variations in macrodiversity, the Amerindian isolates retained functional secretion system machinery, suggesting that the changes are non-deleterious to pathogenicity island function, and are likely under neutral or positive selection.  Strikingly, our study reveled that patients with a high proportion of Amerindian ancestry who are infected with H. pylori strains that have a substantial percentage of African lineage (>20%) develop the most severe gastric lesions. Perhaps the frequent differences in macrodiversity found in Amerindian H. pylori isolates are essential for maintenance of host-microbe phylosymbiosis in the native Colombian population.

The results of our study provide insight into an ongoing debate in the field regarding classification of H. pylori as a pathogen rather than a commensal.  While it is true that H. pylori colonization is associated with a significantly increased risk for development of gastric disease, H. pylori may provide some benefits to its host.  For example, it has been suggested that H. pylori colonization is protective against development of esophageal reflux, cancer of the upper stomach, and cancer of the esophagus.  H. pylori may help to prevent Mycobacterium tuberculosis infection from progressing to active tuberculosis, and may play a role in providing protection from development of asthma and other allergic diseases.  The protective advantages of this fascinating microbe are intriguing, but nonetheless, additional investigation will be required to determine the mechanisms by which H. pylori provides such advantages to its host.  Our study points towards co-analysis of host and microbe genomic variation to identify those at highest gastric cancer risk so that we can selectively target H. pylori eradication.

Finally, our study brings new perspective to the so-called ‘African Enigma,’ a theory that describes the discordant prevalence of H. pylori infection and H. pylori-related disease in continental Africa.  Our findings suggest that maintenance of a harmonious host-microbe phylosymbiotic relationship can account for the low incidence of gastric disease throughout Africa in spite of H. pylori colonization rates estimated at greater than 90%.  In future investigations, it will be important to recapitulate our findings in cohorts from diverse sites including Africa, East Asia, and additional locations within Central and South America in order to determine the extent to which human-Helicobacter phylosymbiosis dictates disease outcome in global populations.

Monday, January 27, 2014

Announcement: Gordon Research Conference on Animal-Microbe Symbiosis | 2015

Very excited to see a 2015 Gordon Research Conference on animal-microbe symbiosis, in addition to the keystone meeting happening now (follow on twitter at #KSinvertebrate). These meetings indicate that the study of animal complexity is driving forward…that zoology requires microbiology.

Animal-Microbe Symbioses
Identifying the Common Language of Host-Microbe Associations
June 21-26, 2015
Waterville Valley Resort
Waterville Valley, NH

Application Deadline
Applications for this meeting must be submitted by May 24, 2015. Please apply early, as some meetings become oversubscribed (full) before this deadline. If the meeting is oversubscribed, it will be stated here. Note: Applications for oversubscribed meetings will only be considered by the Conference Chair if more seats become available due to cancellations.

Animals are intimately associated with a complex community of mutualistic microbes that are essential for their development, nutrition, and health. Research on animal ­microbe symbioses (we use the general term here to denote beneficial associations) has recently become highly active, after decades at the margins of mainstream biology. This renaissance has come from major advances in methods for studying uncultivable organisms such as molecular biological techniques (e.g., the ‘omics’) and imaging methods that can combine information about identity and function at the single-cell level. These and other new approaches are providing novel and unexpected insights into the biology, ecology, and evolution of mutualistic associations between animals and their microbiota. Correspondingly, there is considerable interest in and excitement about the animal microbiome, as visible in numerous papers in high-ranking journals and articles in the popular press. Remarkably, however, there is no regular meeting that focuses on the biology, ecology and evolution of animal - microbe symbioses.
The new Gordon Research Conference on Animal-Microbe Symbioses will provide a stimulating and international platform for understanding the current state of knowledge in this rapidly evolving and vibrant field. By bringing together scientists that work on symbiotic associations from a wide range of host and microbial groups, and are at the forefront of their fields, we will create a diverse and multidisciplinary forum for discussing the newest research directions, debating key questions, and identifying unresolved issues. We will invite researchers from other disciplines such as plant symbioses and pathogenic associations to expand our knowledge and discuss the commonalities and differences among host -microbe associations. Student and postdoctoral attendance will be encouraged by emphasizing the collegial nature of the conference, and the many opportunities for discussion during formal and informal meetings and the poster sessions. The meeting will not only contribute to a better understanding of basic biological research questions such as how prokaryotes and eukaryotes have evolved through mutualistic interactions, but will also be valuable for applied research. For example, pharmaceutical and biotechnological companies are investigating bioactive compounds produced by invertebrate symbionts as valuable, novel, antimicrobial and chemotherapeutic agents, and symbiotic microbes such as Wolbachia may help prevent the spread of human viral diseases such as dengue fever through insect hosts. We are thus confident that a diverse and multidisciplinary community of speakers, discussion leaders and attendees will provide the stimulus for a unique conference in the field of animal-microbe symbioses.

Preliminary Program
A list of preliminary session topics and speakers is currently being developed by the Conference Chair and will be available by December 1, 2014. Please check back for updates.

Wednesday, January 22, 2014

The Hologenome Facebook Page - Discover Your Symbiotic Complexity
I'm happy to announce a sister site on Facebook dedicated to understanding who we are as animal-microbe chimeras - who we are beyond the skin we're covered in. Come join us as we track the history and future of the science of the Hologenome - an "eyes up" view of the symbiotic complexity of organisms. The page starts with a 20 year old video on the topic.

A recent publication in PNAS by 26 luminaries in the life sciences echoes the inspiration for the site: 
"These new data are demanding a reexamination of the very concepts of what constitutes a genome, a population, an environment, and an organism. Similarly, features once considered exceptional, such as symbiosis, are now recognized as likely the rule, and novel models for research are emerging across biology. As a consequence, the New Synthesis of the 1930s and beyond must be reconsidered in terms of three areas in which it has proven weakest: symbiosis, development, and microbiology (115). One of these areas, microbiology, presents particular challenges both to the species concept, as formulated by Ernst Mayr in 1942, and to the concept that vertical transmission of genetic information is the only motor of selectable evolutionary change"
Where we go from here is up to us. This community site is one additional means to an end to see where the hologenome takes us. Looking forward to seeing you there.

Wednesday, December 4, 2013

Do Hosts Handpick Their Microbiome?

I found this microbiome talk from 2011 by John Rawls today and thought it would be good to share here. The work addresses the question of whether gut microbial communities are specific to their host species. Basically, he asks:


If you follow this blog, you'll know that we have discussed a series of studies that indicate microbiomes are uniquely qualified for their host species, sometimes in ways that the phylogeny of the animal yields the same relationships as the "phylosymbiosis" pattern (guest blog post) in the microbial community. These discoveries are important because they emerge out of an initial paradigm in which studies within species have shown variation in the microbiome upon changes in diet or disease. But comparative biologists who think in ecological/evolutionary ways have started to illuminate the rules of microbiome assembly across different species.

It's now safe to say that in the last few years, we have gained a clear understanding that under controlled laboratory studies, the crosstalk between microbiomes and host genomes is undoubtedly intimate, clear, and specific. The gut microbial community is strongly shaped by host selection, perhaps even independently of a phylosymbiosis pattern from 16S data (Oh et al 2010, ISME). If we understand the molecular signals between this conversation, then we can better understand superorganisms (our genes + microbial symbionts) in evolutionary and applied ways.

Human Microbiome Project - John F. Rawls, University of North Carolina at Chapel Hill from Kavli Frontiers of Science on Vimeo.

Wednesday, November 20, 2013

Microbiology Video: "We owe them our very lives!"

It is no secret that many readers of this blog are awestruck by the universality, diversity, and significance of microbes. Indeed, Earth is a “microbial planet” in the sense that the oldest (over 3.8 billion years ago) and most abundant forms of life are the ones too small to be seen by the unaided eye. Even more powerful is the quote in the video that "We owe them (bacteria) our very lives".

If you ever want to share those sentiments with friends, family, students, colleagues, or heck, politicians - then this new HD cinematic video is a perfectly simple introduction. Check it out….it is worth the four short minutes and then some.

By NIAID_Flickr [CC-BY-2.0]
via Wikimedia Commons

Related blog posts:
The Gravity of Symbiosis (Nov. 3, 2013)

Wednesday, November 13, 2013

Does the Federal Government Slow Innovation and Markets?

You think you know, but you have no idea.

This talk takes a sledge hammer to the idea that government funding of science and technology is a waste and slows innovation. At a time when everyone needs to heed the call that American science is broken, this talk single-handedly champions the idea that government IS the risk taker in the market, rather than the risk-fixer.

The internet, gps, Siri, touchscreen, etc - all stated below to be birthed with seed money from the Uncle Sam. Bottom line, if you like your cell phone, then you will like the next thing (federally-funded) scientists and engineers create too.

Stand up for congressional members and candidates that support science for they in turn will make funding decisions that will support future luxuries of a modern world, not to mention a growing stock market spurred by revolutionary products.

Thursday, November 7, 2013

Blow Your Mind Podcast on Da Hologenome

Most Recent Episode:

Into the Hologenome

1 day ago31 minutes

How can the bacterial fauna thriving inside our bodies influence evolution? Find out in this episode of Stuff to Blow Your Mind.

Sunday, November 3, 2013

The Gravity of Symbiosis

This post is lifted from my blog at the International Symbiosis Society's website, which just started a blog series by members of the community to foster dialogue and debate. I thought that I would post it here as well because it continues a stream of posts here on the fusion of the microbiome and evolutionary sciences from the vantage point of our laboratory's work. I think the last paragraph is perhaps the most salient, so either skip ahead or follow through.

View From 32,000 Feet

Darwin and the 20th century pioneers of biology would have been astonished to see the countless roles that microbes play in shaping eukaryotic life. From the origins of eukaryotic cells to pharmaceutical products, Life as we know it would be unrecognizable without microbes. Integrating microbes into all facets of the life sciences today is a vision that is not only driven by exciting questions at the perimeters of the biological disciplines, but one that seems more achievable today than ever before, at least from a our vantage point within the symbiosis field.

Let us briefly look backwards in order to look forwards. The fusion of evolutionary biology and Mendelian genetics spurred a modern synthesis in which the biologist sees the world through a refined set of filters: the genome is stably inherited, subject to natural selection, and defines who we are as individuals and how species arise from descent with genetic modification. Yet there is a transformation occurring today in our capacity to understand who we are beyond our nuclear genes.Indeed, biologists take the archetypal examples of mitochondria, chloroplasts, and endosymbionts for granted, but the science of the microbiome has emerged in the last decade to massively widen the recognition, if not scope, of Life's dependency on microbes. One luminary in our field lost to history, Prof. Ivan E. Wallin, remarked in 1927:

"It is a rather startling proposal that bacteria, the organisms which are popularly associated with disease, may represent the fundamental causative factor in the origin of species"

Below I will summarize our most recent foray into speciation by symbiosis. This post is far too small to give a full and fair treatment of the topic, and I apologize to my colleagues in advance for not citing their work.

From Many Genes and Microbes, One Species

Approaches to studying the gut microbiome in animals have largely been diet- and disease-centric. Relatively little is known about the comparative structure and evolution of bacterial communities among closely-related host species, but this knowledge gap is starting to change. For instance, as speciation events progress from incipient to complete stages, does divergence in the composition of the host-associated microbial communities parallel the divergence of the host's nuclear genes? (Brucker and Bordenstein 2012a link) We hypothesized that if host phylogenetic relationships, in part, structure gut microbial communities, then related species of animals reared on the same diet will not acquire the same microbiome, but instead host species-specific communities of microbes. We discovered that the gut microbiome was indeed different between closely related species of insects reared on the same diet, and the constituents and composition of the bacterial communities in each species changed in parallel with the genomic relationships of the host species (Brucker & Bordenstein 2012b, link) - a pattern we have since termed "phylosymbiosis" (Brucker and Bordenstein 2013 link, and Figure 1 below).The significance of phylosymbiosis is also evident in primates (Ochman et al. 2010, link) and hydra (Franzenburg et al. 2013, link).

Figure 1.Phylosymbiosis. Like phylogenomics, phylosymbiosis is a total microbiome metric that retains an ancestral signal of the host's evolution. (a) The central prediction is that divergence in host genes is positively correlated with differentiation of the microbiome. (b) Parallel dendrograms between the host phylogeny and the microbiome relationships is one test of phylosymbiosis (c) Schematic of a real data example from our model study system.

We recently tested the hypothesis that the gut microbiome assists animal speciation, even in the well-studied Nasonia genus where nuclear speciation QTLs were genetically mapped to chromosomes. First, we demonstrated that gut bacterial diversity in F2 hybrids goes markedly awry in comparison to that of pure species controls (Bordenstein and Brucker 2013, Science, link). Second, curing this altered gut microbiota eliminated hybrid lethality (Figure 2), the misexpression of immune genes associated with hybrid lethality, and marker ratio distortions away from Mendelian inheritance for speciation QTLs. Finally, we recapitulated hybrid lethality in germ-free hybrids by orally inoculating them with resident strains of the dominant bacteria within species. Thus, in a series of "gain" and "loss" microbiome experiments, we demonstrated that reproductive isolation in this genus is not dependent solely on genetic divergence, but also on the interactions between the host genome and gut microbiome. It is enticing to speculate that this phenomenon will be common in animals since they all have a gut microbiome that is increasingly seen to affect numerous aspects of fitness. Time and experimentation will tell. A simple experiment would be to test if hybrid inviability can be cured in diverse germ-free systems.

Speciation by symbiosis has been subject to healthy skepticism. For example, one interpretation of the data above is that the gut microbiome is just an environmentally conferred stress on the wasps’ fitness, and hybrids are hyper-susceptible to this stress. So the presumed stress of microbiome colonization on hybrid wasps can be compared to a predator eating hybrids more than the vigorous parentals that escape predator detection. However, in this argument, the microbiome is seen as purely extrinsic to the host. Like all metazoans, Nasonia's gut microbiome is inevitable and plays a large beneficial role in host fitness - survival and reproduction. Thus, removal or suppression of the microbiome in Nasonia is quite maladaptive, causing a ~15% decrease in survival from egg to pupal stages (Brucker and Bordenstein, 2012, link) and delayed development into adulthood by two to three days. Thus, in contrast to an extrinsic predator, the narrative here is that microbiome is essential for within-species fitness. Similar to a beneficial set of genes, the microbiome is also causal to reproductive isolation in hybrids, much like the way a classical geneticist studies speciation genes that are adaptive within species but break down in hybrids.

Figure 2. Hybrid lethality in Nasonia. Top: Non-hybrid 3rd instar larva. Bottom: Hybrid 3rd instar larva that is melanized and dead.

The Gravity of Symbiosis

The term "holobiont" is used to define the host and its collection of beneficial symbionts. It does not differentiate intracellular or extracellular symbionts as it is a lens to view the individual as an engineered collection of organisms. Therefore, the term "hologenome" naturally follows as a definition of the total genetic material of the holobiont. The hologenome emphasizes that the animal’s genome, mitochondria and beneficial microbiome are an aggregate of genes that together form a unit of natural selection (Zilber-Rosenberg and Rosenberg, 2008, link). To be historically accurate, the term hologenome was originally and independently proposed in 1994 by Richard Jefferson in a seminar on PCR technology (YouTube link). The evidence motivating these terms spans the essential roles of the microbiome in eukaryotic fitness (McFall-Ngai et al, 2013, link), including digestion, immunity, olfaction, organ and neuronal development, etc.

However, the hologenome concept is controversial, perhaps more so than the holobiont. These terms are gaining attention but are still rather new to biology and should be subject to questions. Some view the individual solely through the refined filter of the nuclear genome. In this case, the microbiome is purely extrinsic to the host animal and therefore unable to co-evolve sensu stricto with the host genome. In order for the microbiome to change in parallel with the host genome, stability of the two genomic units by vertical transmission or host selectivity in microbiome community structure is required. Current evidence specifies multiple paths for stability that we must delve much further into.  For example, maternal microbial transmission may be universal in animals for some fraction of the microbiome (Funkhouser and Bordenstein, 2013, link) and specificity provided by the host immune system can further cement the essential foundation for host-microbiome stability and co-cladogenesis (as evident in phylosymbiosis).

In Nasonia, the phylosymbiotic associations of parental host genes and microbes are both required for fitness within species, but are in negative epistasis in hybrids undefined comparable to nuclear-nuclear and cytonuclear gene interactions that function normally within species but cause hybrid incompatibilities.  In this light, the discovery of the phylosymbiotic gut microbiome can be understood as part of a co-adapted unit, which functions normally within species, but breaks down in hybrids between species.

Of particular relevance is that the vital fitness traits conferred by the gut microbiome within species blurs the lines between what biologists conventionally define as the environment or the organism. And perhaps this point is the most salient. Intrinsic and extrinsic views of the microbiome are largely semantic filters placed on our definition of the individual. Nature may not care about this linguistic argument. What matters is stability of the associations, no matter if we define them as intrinsic genome-by-genome or extrinsic gene-by-environment interactions. Today, it is convention that mitochondria represent anciently acquired bacteria that have a fully integrated partnership with the animal genome. The continuum of symbiosis stretches from these obligate relationships of endosymbionts to the host farming the microbiome.

I extend my thanks to the ISS board for asking me to write this blog post and for you reading it. I look forward to reading your future posts and extending this social medium to the symbiosis community.

Warmest regards,