How Microbiome Research is Changing Our Understanding of Evolution

body-dnaEvolution via natural selection has served as a guiding principle in biology for more than a century. This powerful idea – which first came to life in Charles Darwin’s book On the Origins of Species – helps explain why organisms are composed of a complex mix of adaptations and trade-offs, how species originate and evolve, and why there is biological variation between organisms.

The beauty of natural selection is that there’s no agent that’s actively selecting; rather, the selective processes occur naturally as a result of variation in reproductive success. Those organisms that are well-adapted to their environment, possessing heritable traits that increase their evolutionary fitness, get on average more offspring than organisms that are less well-adapted. In that sense, natural selection acts to preserve what has worked in the past.

For the longest time, the dogma has been that animals and plants primarily adapt to their environment through changes in their own genome, and that evolutionary forces act at the level of an individual organism. However, over the last decade – and in particular the last couple of years – it has become clear that these notions may be too simplistic…

The current paradigm

Natural selection acts on genes and on the individuals that carry them. To illustrate this concept, let’s have a look at what happened when our ancestors introduced milk and other dairy foods into their diets. In the Paleolithic, no humans consumed milk from another species on a regular basis. This changed about 8.000-10.000 years ago, when the Agricultural Revolution started spreading across the globe and we began domesticating animals.

At first, few of our ancestors possessed the enzymatic functions needed to digest lactose post-infancy; however, as the time went on, the prevalence of lactase persistence increased, particularly in Northern European countries, which today house the largest numbers of lactose tolerant individuals in the world.

This process occurred because genetic mutations associated with lactase persistence were under strong positive selection. Individuals who were able to digest lactose without gastrointestinal distress were able to broaden their diet to include dairy foods, and they thereby had access to a new source of calories, something that favorably affected their Darwinian fitness. On average, the individuals with a lactase persistence phenotype experienced elevated reproductive success when compared to lactose intolerant individuals, particularly during times when non-dairy foods were not as abundant. Hence, the prevalence of lactase persistence increased.

Selective processes such as the one above are generally believed to occur through the selection of genes within each single organism’s own genome. However, what we’re now learning is that it may be time to reconsider this belief.

Recent research is challenging long-standing beliefs regarding how macroscopic organisms adapt to their environment

Animals are not sterile; rather, they harbor complex communities of microorganisms. A general rule of thumb is that microbes occupy animal surfaces that are in some way exposed to the outside world. That said, they also sometimes make their way into more enclosed spaces. These microbial symbionts carry out essential functions that the host lacks the genetic capability to perform itself

As for humans, we all carry a unique microbiome – the collective genome of the microorganisms – which complement our own genome. In other words, the composition of the microbiome varies between individuals. This is important to keep in mind in the discussion of evolution, because variation is a prerequisite for natural selection to occur.

A microbiota that is beneficial in one environment may not be ideally suited for another milieu. The good, or bad, thing, depending on how you look at it, is that the microbiota is very flexible. When compared to the human genome, which stays relatively stable over generations, the microbiome is highly malleable.

By having a microbiome we are able to adjust to new environmental conditions much more rapidly than what would have been possible if we were dependent solely on changes within our human genetic code. These processes can occur in several different ways. During our lifetime, we’re exposed to trillions of microorganisms, some of which may set up shop somewhere on our body and/or transfer genetic material to bacteria that are already present. These novel microbes may affect our evolutionary fitness, for example by impacting our cold tolerance or digestive capabilities.

The microbiota can also aid our survival in a given environment through other means. For example; when we change our diet, the microbiota adjusts. The gut microbes that do well on the new feed expand in numbers, while the communities of microbes that are less well adapted to the new environment diminish in size.

In summary, we’ve known for quite some time that microbes are integrated into the biology of larger, eukaryotic organisms such as humans. However, recently we’ve started to understand that this relationship is a lot more complex than previously thought.

How microbes affect our evolutionary fitness

Okay, let’s do a couple of examples to illustrate how the microorganisms associated with a larger organism can affect that organism’s ability to survive and reproduce.

First, let’s continue with the example of lactase persistence from the first section. The long-standing belief in nutrition has been that individuals who don’t carry lactase persistence alleles will never be able to digest lactose without experiencing gastrointestinal distress. Recent research, however, suggests that this is not necessarily the case. Several studies have shown that consumption of fermented milk products (e.g., kefir) or probiotic supplements can alleviate symptoms of lactose intolerance (1, 2, 3). How could this be?

The answer is probably not complicated. Yoghurt, kefir, and other similar fermented dairy foods all contain bacteria carrying genes that code for enzymes that facilitate the breakdown of lactose. When we consume these foods, some of the microbes found within them may initiate lactose-digesting processes during their passage through the gastrointestinal tract. It may also be that they find an available niche in our body or leave some genetic material behind, thereby permanently enhancing our ability to digest lactose. In other words, we’re adapting to break down lactose through changes in our microbiome, rather than through changes in our own genome.

The studies so far have only showed that probiotics can improve lactose digestion, rather than completely cure lactose intolerance; however, I suspect that if the right foods are consumed and the microbiota is given sufficient time to adapt to a lactose-containing diet, symptoms of lactose intolerance may largely be eliminated.

Similar processes occur in the gastrointestinal tract of other animals. Cows are particularly interesting in this regard, as microbes play an extremely important role in their digestive machinery. The bacteria, fungi, and other organisms that live in the rumen of cattle enzymatically convert cellulose and other feed components into sources of energy that can be absorbed and used by the host. Without these symbionts, the cow doesn’t get the volatile fatty acids it requires to survive. In other words, a cow’s ability to survive and reproduce isn’t only determined by the mix of traits that arise from its own genome, but also by its symbionts and their genetic potential.

The microbiota can also acutely affect an organism’s survival, such as in the case of infections. This can clearly be seen in hospitals all over the world, where you’ll find patients infected by the bacteria Clostridium difficile. This microorganism – which is killing people who don’t receive proper treatment – is only able to set up shop in the digestive system of individuals who carry a microbiota that has been severely disturbed (e.g., due to multiple rounds of antibiotics). If a healthy, diverse microbiota is present, C. diff isn’t able to find a niche or rapidly expand in numbers.

Our microbiota can also affect our survival and reproduction in other, more subtle ways. Microbes have far-ranging effects on our immunity, metabolism, brain function, and hormonal system. It has become increasingly clear to me over the years that the microbes associated with a human host can affect the host’s reproductive fitness through its impact on these components of our biology. Infertility, depression, impotence, and miscarriage are just some of the many conditions and events that are associated with chronic low-grade inflammation, which is tightly interlinked with dysbiosis and lack of microbiota diversity.

These examples are all used to illustrate the fact that the microbiota associated with a larger organism (e.g., human) is unique to that host, changes in accordance with environmental stimuli, and affects the host’s ability to survive and reproduce. The question then becomes, is the microbiota passed down through generations? If so, it certainly has to be considered in the context of the evolution of macroscopic organisms. This leads us over to the hologenome theory of evolution…

The hologenome theory of evolution

The hologenome theory of evolution proposes that evolutionary forces acting at the level of an individual organism (e.g., a single plant or animal) are instead acting on the “holobiont” – the inherent community of a host plus all of its symbiotic microbes. As selection operates on phenotypes, classic individual selection is effectively selection on the holobiont. Consequently, the collective genomes of the holobiont form a “hologenome”. Variation in the hologenome encodes variation in phenotypes upon which evolutionary forces such as selection or neutrality can operate. (4)

In today’s article I’ve primarily focused on natural selection; after all, the website is called Darwinian-Medicine.com. However, as noted in the quote above, other evolutionary forces are also important to consider in the context of the hologenome theory of evolution; a theory that has gained increased attention in the scientific community over the last 8 years (5, 6, 7).

For the hologenome theory of evolution hypothesis to be true, it has to be shown that all of the conditions required for evolutionary processes to occur are being met. In the previous section I showed that it’s well established that some of these conditions, such as those that revolve around variation and the ability of microbes to affect the fitness of larger organisms, are fulfilled. However, this is not sufficient to conclude that evolutionary forces act at the holobiont level, rather than at the level of individual organisms.

The hologenome theory of evolution is debated, and some scientists have criticized the theory, stating that it has some flaws and that a lot more data are needed before it can be determined whether a paradigm shift in evolutionary biology should be considered (8, 9).

The biggest concern at the moment is that we don’t know to which extent the microbiota is transmitted across generations. As for our species, it’s well established that microbes are transmitted from parent to offspring by a variety of methods, including via cytoplasmic inheritance, coprophagy, direct contact during and after birth, and the environment. What we don’t know, however, is how much of the microbiota that is passed on.

Is it possible that the microbiome is passed on in its totality, or do we just receive bits and pieces of it? The current evidence indicates that the answer may lie somewhere in between. This leads us then to another question: Should we continue to operate under the belief that evolutionary forces act at the level of individual organisms, or should we start to include microbes into this facet of evolutionary theory? For example, if a woman doesn’t carry lactase persistence alleles, but is able to digest lactose because she harbors lactose-digesting microbes, should we then assume that these microbes are passed down to her offspring?

At the moment, it’s difficult to answer these questions, as the necessary studies haven’t been done. It will be very interesting to see what the research in this area will show in the coming years.

So, to summarize; at present, it’s premature to make firm conclusions regarding the accuracy of the hologenome theory of evolution. That said, I think it’s already safe to say that the expanding research on microbiomes associated with plants, animals, and other living organisms are changing our understanding of how evolution works, and that we need to more carefully examine the role microbes play in the evolution of plants and animals.

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Comments

  1. Very interesting, I breed Barzona cattle, have had a closed genetic herd for over 37 years. Improving the Bacteria, fungi ect. has had the most beneficial effects on the ranch, cattle, wildlife, the whole in general. I would be interested in more material on this subject.

  2. Alessio says:

    Thought provoking. The hologenome theory is fascinating, though, as usual, certain interpretations make me skeptical.
    Browsing on the web I’ve found a scary probiotic campaign that is supposed to help us to digest gluten and even heal celiac disease through 2 species of bacteria of the Rothia family. Doing a brief research I’ve found that they are associated with pneumonia, endocarditis, sepsis etc..
    Thus, the point is: microbiome can adapt quickly, but is our body supposed to harbor such species? If eating gluten make me harbor the aforementioned species and they trigger diseases, it’s pretty much clear to me that it’s not such a good idea having these guys around my body. And this leads me again to my genome…

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