Should Evolution Treat Our Microbes as Part of Us?
How does evolution select the
fittest “individuals” when they are ecosystems made up of hosts and their
microbiomes? Biologists debate the need to revise theories.
Microbiome science has revealed
the deep interdependencies of animals and plants on their microbial partners,
prompting calls for an expansion of evolutionary theory.
Andrew
Rae for Quanta Magazine
November 20, 2018
Twilight falls on the Tanzanian
plain. As the sky turns a deeper purple, a solitary spotted hyena awakens. She
trots along the border of her clan’s territory, marking the boundary with a
sour paste from under her tail. She sniffs a passing breeze for hints of
itinerant males interested in mating, giving little attention to her stomach’s
rumbling over the remnants of the previous night’s hunt or the itch on her
flank. The lone hyena chooses what she will do next to make her living.
Except she is not alone. That
paste she secretes is produced not by her own cells but by billions of bacteria
housed within her scent glands. The scents on the breeze from potential mates
also come from unique microbial concoctions. A diverse array of bacteria that
line her gut are helping to break down her meal. Others assist her immune
system in fending off the hordes of parasites and pathogens trying to invade
her skin and other tissues.
Who precisely is it, then, trying
to survive on the Tanzanian plain? Can we consider the fates of the hyena and
the microbes within her independently? Or does their interaction form something
new, greater than each part alone?
“We’ve underestimated the
potential contribution of microbes to traits we’ve been studying for decades or
centuries,” said Kevin Theis, a microbiologist at Wayne State
University who studies the paste-making microbes of the hyena. “If the genes
for these important traits are actually in the microbiome and not the animal
itself, then we need to take a systems-level approach and look at the
host-microbe system as a whole.”
Kevin
Theis, a microbiologist at Wayne State University, believes that evolutionary
science needs to look at host-microbe systems as a whole.
Courtesy of Kevin Theis
Look closely enough at any plant
or animal and you will discover a riot of bacteria, fungi and viruses forming a
complex and interconnected ecosystem. A recent explosion of research reveals
how deeply we rely on our microbial patterns to keep our bodies functioning,
raising profound questions about what it means to be an individual.
Vital functions like digestion
and immunity were long assumed to be under the purview of individual organisms,
as capabilities developed and were refined through evolution by natural
selection — the differential survival and reproduction of individuals. But if
our bodies are less an autocracy of identical cells and more a coalition of
multitudes, how can we explain their evolution?
Some biologists are calling
for a radical upgrade of evolutionary theory, arguing
that prevailing ideas, developed from the study of bigger, more easily
understood organisms, don’t fit nicely into this new world. Others contend that
existing theory just needs to be applied more carefully. All agree that the
micro and macro worlds are inescapably interdependent, and that biologists must
explore the frontier of their interconnections.
Never Alone
“We have never been individuals,” proclaimed a
2012 paper in The Quarterly Review of Biology by Scott Gilbert, a developmental biologist at
Swarthmore College, and his colleagues. This bold assertion echoed previous
calls for a reconceptualization of complex organisms as new kinds of
individuals — holobionts. The term holobiont encompasses a host animal or plant
and all its constituent microbes. All genes within a holobiont, belonging to
host or microbes, constitute the “hologenome.”
Holobionts and hologenomes are
“incontrovertible realities of nature,” wrote Theis and his colleagues in the
journal mSystems. Hologenomes contain vastly more genes than the
host genome alone, and since at least a fraction of the microbial genes have
significant bearing on the survival and reproduction of the host, we need to
consider the hologenome as a possible unit of selection if we want to
understand the evolution of the holobiont.
“First and foremost, I think of
the holobiont and hologenome as structural definitions,” said Seth Bordenstein, an evolutionary biologist at
Vanderbilt University. Along with other researchers, Bordenstein argues that
fresh language is needed to refer to this entity, given the ubiquity of
host-associated microbes in nature. “We accept the chromosome or the genome as
structures. The next level up is the hologenome,” he said.
Seth
Bordenstein, an evolutionary biologist at Vanderbilt University, argues that
the ubiquity of host-associated microbes in nature suggests that “holobionts”
need to be recognized as meaningful units.
Courtesy of Seth
Bordenstein/Vanderbilt University
“The secondary question is: Does
the hologenome matter?” he continued. No one knows what proportion of the
microbiome will influence host fitness; many are surely just along for the ride.
But if there is some degree of cooperation — for instance, if the host provides
shelter or nutrients for some microbes that in return metabolize products the
host can’t make on its own — then they are more than just two organisms
occupying the same space. They are, to a degree, functionally integrated. And
that raises the question of whether the hologenome might also matter
evolutionarily.
The tighter the integration, the
more closely intertwined the fates of host and microbe become. For such
holobionts, Bordenstein says, you can’t understand the evolution of either the
host genome or the microbial genomes in isolation because the community of
organisms as a whole shapes the traits of the individual. “We need to
understand what the microbes make, what the host makes and potentially how
those products work together,” he said. The holobiont, he argues, adds up to
more than the sum of the host and microbes. Out of their interaction emerges a
coherent entity that natural selection might act on alongside other units of
selection, like the individual or a gene.
Proponents of this hologenomic
concept of evolution argue that if there is a fidelity across generations
between hosts and microbes, then the holobiont embodies a coming together of
numerous, disparate evolutionary lineages into a singular being, a coalition of
many that contributes to the functional integrity of the whole. Only when
considering the holobiont as a single entity capable of being shaped as a unit
by natural selection can we make sense of its complexities.
Variation and Heritability
What might it mean for a
holobiont to evolve through natural selection? How can traits emerging from the
holobiont as a whole rather than from any individual line of cells in it be
“chosen” by nature and spread in the population? The classic recipe for
evolution by natural selection begins with a population of individuals with
varying characteristics that affect the number of viable offspring they are
likely to have. Those characteristics must be inheritable — that is, passed on
with some fidelity from generation to generation. A trait could hypothetically
double some lucky individual’s lifespan and number of offspring, but unless
that trait gets passed on, it’s an evolutionary dead end.
Lucy Reading-Ikkanda/Quanta
Magazine
Do holobionts meet those criteria
for evolving entities? Microbes and host genomes can interact in ways that
profoundly affect host fitness. But whether we inherit our microbiome in
something like the way we inherit our genome remains a point of contention.
Parents do pass along microbes to
their offspring. For example, females of some species of stink bug nestle a
fecal pellet near freshly laid eggs to serve as the larvae’s first meal,
thereby inoculating them with their mother’s gut microbiome. Typically, human
babies not born by cesarean section acquire their mother’s vaginal microbes en
route to the outside world. Mom’s microbes also rub off on a baby through close
contact and breastfeeding. Although eventually the microbial community changes
as the child moves more freely through the world, these early microbes play an
outsize role in immune system development.
Not all of the microbiome is
transferred from parent to offspring, but according to Bordenstein, it doesn’t
have to be. “Nobody I know expects the microbiome to be inherited in its
entirety, faithfully,” said Bordenstein. But if a significant portion of it is,
he and others argue that those interactions and their evolution might be
understood as a unit of selection.
Poking Holes in Hologenomes
Other researchers think the
hologenome concept of evolution stretches the notion of a selectable unit to
the point of incoherence. “Just because the microbes are there with one
organism at one time does not mean they are a unit of selection, especially if
they are not passed on vertically,” said Joan Strassmann, an evolutionary biologist at
Washington University in St. Louis who studies microbes.
“I don’t want to make the strong
claim that vertical transmission is absolutely necessary, but it’s certainly
the most likely mechanism to lead to the cumulative evolution of the
partnership as a whole,” said Derek Skillings, a
philosopher of biology at the University of Pennsylvania and the City College
of New York.
Skillings and other critics argue
that there just isn’t enough evidence of vertical transmission of symbionts to
allow for the holobiont to be a coherent evolutionary individual. Many of a
host’s microbes are acquired from the outside environment, not from its
parents. Even when the environment is shared, there is little reason to assume
that a parent’s microbes will make it to its offspring. Even if they’re the
same sorts of microbes, the direct line of vertical transmission is still
necessary to form an evolutionary individual.
Just because the microbes are
there with one organism at one time does not mean they are a unit of selection
…
Joan Strassmann, Washington
University in St. Louis
Skillings further argues that the
repeated co-occurrence of species in nature does not imply that they have
shared interests. Consider a host and a parasite locked in perpetual conflict:
Every generation, they come together and attempt to subvert each other. You
could even imagine a familial line of hosts being infected by the same familial
line of parasites. Nevertheless, persistent as this relationship is, Skillings
argues that you’re only going to understand it by considering each lineage’s
interests separately. Proponents of the hologenome concept acknowledge that
cooperation, conflict and even neutrality can influence the evolution of the
holobiont, making the disagreement less about the facts of the matter, and more
about how to approach them.
Strassmann argues that focusing
solely on what’s happening in the holobiont misses much of the microbes’ story.
Many host-associated microbes spend significant chunks of their lives outside
their host, in an environment where they’re subject to very different selection
pressures. The holobiont idea, she says, puts blinders on our understanding of
the evolution of these microbes, focusing attention on the host environment and
neglecting other habitats that could shape a microbe’s character.
Critics of holobiont-centered
theories are not discounting the importance of studying the interconnections
between microbes and hosts, but they think the holobiont framework is almost
always misleading. They envision the holobiont as an ecological community, not
an evolutionary individual. The knowledge that symbiotic relationships with
microbes are important “doesn’t mean we have to completely forget what we know
about how evolution and natural selection operate,” Strassmann said.
But translating existing
ecological and evolutionary theory to this new microbial world is more easily
said than done, cautions Britt Koskella, a biologist at the University of
California, Berkeley. Many of these theories were built to explain how plants
and animals interact and coexist, and “there are well-understood aspects of
microbial ecology that just don’t fit here,” she said.
Joan
Strassmann, an evolutionary biologist at Washington University in St. Louis,
thinks that a hologenome concept of evolution pushes the idea of selectable
units too far.
Joe Angeles/Washington University
Take ecological succession, a
framework for evaluating how a community assembles over time. The state of a
plant community on a new island, for example, may depend much more on the order
in which species arrived and the niches they filled than on the local evolution
of the plants, because evolution is usually so much slower.
But bacteria evolve much faster
than plants and animals, and they can swap genes instantaneously via horizontal
gene transfer. “Now you have to consider the possibility that a microbe could
arrive and, whether by mutation or horizontal transfer, fill all available
niches before anyone else shows up,” Koskella said. Bacterial succession might
work in different, counterintuitive ways from traditional succession.
Other differences to consider,
according to Koskella, include the influence of a host’s immune system over its
microbiome and microbes’ ability to dynamically alter their environment. She
argues that theoreticians need to think through basic assumptions made by their
models and consider whether they apply equally well to microbes, and
empiricists need to test the predictions of those models. “Cross-talk between
empiricists and theoreticians is really important,” Koskella said. “The data
are just so complex, and we’re very quickly moving beyond intuition.”
Settling empirical questions,
such as how often a substantial portion of the holobiont is inherited, and how
stable communities are across generations, will help sharpen intuition and
inform theoretical work. “We can keep just asking questions and getting data,
but without theory, you don’t really know how to begin interpreting or testing
all this complexity,” Koskella said.
It’s the Song, Not the Singer
One radical idea seeks to forge a
third way forward by turning the problem on its head. Forget about the
particulars of which microbes are doing the interacting or whether they’re
vertically or horizontally transmitted, its proponents say — just focus on the
interactions, the stable metabolic processes enacted by various microbial
players.
“It’s the song, not the singer,” said W. Ford Doolittle, an
evolutionary biologist at Dalhousie University in Nova Scotia. He and his
former Dalhousie colleague Austin Booth originated this idea and gave it its
name, abbreviated ITSNTS, by inverting the title of a Rolling Stones song. They
argue that it captures what’s so compelling about the idea of holobionts,
namely the stable networks of interaction patterns among disparate lineages,
without ascribing a special evolutionary identity to them. Instead, the processes themselves form a sort
of evolutionary lineage.
W.
Ford Doolittle, an evolutionary biologist at Dalhousie University in Nova
Scotia, is one of the authors of a new evolutionary concept in which stable
patterns of metabolic interactions among hosts and microbes — but not
necessarily the organisms themselves — might serve as a unit of selection.
Courtesy of Ford Doolittle
Doolittle and Booth begin from
the observation that gut microbiomes contain a wide diversity of species and
strains across many bacterial taxonomic groups but exhibit a remarkable
conservation of core functions performed by those organisms. These networks of
different players participate in metabolic cycles, in which a set of bacteria
converts nutrients to metabolites, which get picked up by other bacteria to
produce a different metabolite, which gets used by the host, and the cycle
continues. Many of these functional steps can be carried out by myriad strains
present in the gut, making any given strain potentially redundant. But the
cycle itself continues, regardless of which cells are enacting it.
Doolittle illustrates the idea
using the nitrogen cycle. Atmospheric nitrogen gets churned through a series of
chemical states by a diverse assortment of bacteria, plants and decomposers
like fungi performing different reactions. Each step in the cycle can be carried
out by innumerable species that all belong to a kind of “functional guild,” but
the process itself remains remarkably stable.
Once these networks exist, they
create a niche for other microbes to occupy. The cycle becomes a sort of
structure for various lineages to grab onto, a way for them to make a living.
“If you make the leap and think of these interaction networks … as populations
of entities, you can begin to understand them as units of selection,” Booth
said. “It turns traditional ways of thinking about evolution on its head. The
materialistic basis of lineages takes a back seat.”
Doolittle and Booth liken this to
the way songs perpetuate themselves as cultural entities. “There are songs
which have lasted for a long time basically because a lot of people were happy
to sing them,” Doolittle said. Individual singers come and go, but even in
cultures where written and recorded music don’t exist, the songs survive by
recruiting appropriate talent in new generations. Similarly, once a metabolic
network exists, diverse lineages of organisms can evolve to perform some of the
interactions and processes that define it — and evolution can support that
association because it is selfishly advantageous for the individuals, or genes,
within the various lineages to do so.
Processes being selected via
differential persistence is certainly an unusual idea, but not unprecedented.
Cultural evolution of ideas in the form of “memes,” while controversial, is
seen by many as at least plausible (the meme concept was itself inspired by the
biological concept of genes). In this case, the idea or meme is the metabolic
interaction, and it persists based on its ability to recruit microbes to carry
it out.
It remains to be seen how useful
this framework might be for studying the holobiont, and significant kinks
remain to be ironed out. The notion that differential persistence is analogous
to differential reproduction might seem strange to many evolutionary
biologists, and it’s still far from clear how to define a metabolic network.
Fertile Ground
Spirited argument over how
evolution fundamentally works is nothing new. “Evolution, if you look at the
history of the idea, has always been beset with these kinds of debates,” Booth
said, referring to early debates about whether evolution proceeded gradually or
in fits and starts.
“It’s safe to say that the
microbial revolution has been impactful in that it throws so many of the
traditional ideas out, or at least casts them in a new light,” Booth said.
“I think we’re just beginning a field here,”
Bordenstein said. He points to the early days of genetics. “Those early
questions were so basic — what is a gene? How are genes inherited?” Biologists
are just starting to get a handle on the basic questions of microbe-host
interactions. “Who’s there? What is the complexity of the holobiont and how do
its parts function together? We have a century’s worth of work ahead of us to
figure this out.”
Strassmann agrees. “It’s really important that we keep talking
to each other. We have so much exploring to do.”
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