Holobiome Theory: Introducing New Dimensions to Biological Sciences




The Holobiome theory opens a new window for our perception of host-microbial interactions. The term “holobiont” was first introduced in 1991 by Lynn Margulis and initially referred to a simple biological entity involving a host and a single inherited symbiont. It was later extended to define a host and its associated communities of microorganisms. The term “hologenome” was introduced more recently in 2007 by Ilana Zilber-Rosenberg and Eugene Rosenberg to describe the sum of the host genome and associated microbial genomes, in other words, the collective genomes of a holobiont.

A new perspective of evolution

Now, instead of viewing an organism and the microbiome inside it as separate entities, they are considered as a large unit, comprising smaller parts, each part retaining its individual identity, but working together seamlessly to create a biological machinery. It can be said that these individual holobionts, rather than just the host organism, comprise the functional unit in a population, and each holobiont in itself consists of numerous populations, each contributing towards the evolutionary forces affecting the holobiont. 

As holobionts are formed by the interaction of an organism with the environment, it can be said that a part of the hologenome is “acquired” by the organism from the environment, reviving theories of Lamarckian evolution. Hence, it might be true that an organism acquires variations from the environment, and these variations can be inherited, just not in the way Lamarck had imagined. Hologenome, or at least parts of it, are inheritable; They inevitably exchange microbes upon close contact between two individuals, even a mother and her child. Any variation in the microbiome caused due to mutations, horizontal gene transfer, recombination, and other mechanisms is therefore, at least theoretically, inheritable.

Evolution in a population is a result of evolutionary changes happening in a holobiont. As stated above, each holobiont will behave as a system composed of multiple smaller populations, and interactions between these populations within a holobiont will affect its evolution by affecting the allelic frequencies of the populations. This is in agreement with the multilevel selection theory which states that selection operates across multiple levels of genetic variation (i.e., genes, chromosomes, genomes, symbionts, communities, species, etc.) with phenotypic effects. Fitness differences, therefore, can arise from host-microbe associations too. An interaction between organisms, say between a pollinator and a flower, can be seen as an interaction between holobionts, following standard ecological principles, hence fitting the hologenome concept perfectly into concepts of genetics. Holobiome theory does not contradict the rules of evolutionary biology. Instead, hologenomes are considered as a major component of the DNA of a holobiont, and like nuclear DNA, they are susceptible to mutations leading to variation, new adaptations and perhaps speciation.  

Tiny but mighty

Although microbial interactions and their significance has been studied for a long time, the full extent of impact of microbes and their role in host biology, ecology and evolution is far from being unravelled. Development of molecular techniques and NGS technologies have certainly provided the momentum and tools needed to recognize microbes as key inhabitants of macroorganisms, and as frontline players in biological and evolutionary processes. 

The human gut contains about 4 x 1013 bacteria, almost equal to the total number of cells in the body. Owing to the diversity, the gut microbiome alone has approximately 9 million unique protein-coding genes, about 400 times more bacterial genes than human genes. And this is just for the bacterial species; the rich diversity of viruses and fungi have not yet been studied extensively.

Interactions between microbiomes and their hosts have been demonstrated to confer better adaptability to the holobiont. Resident microbes protect the host against pathogens. In general, germfree animals are more sensitive to allergies and infection by pathogens than conventional animals. Many resident microbes produce antibiotics which play an important role in protecting the holobiont against pathogens. In other cases, microbes carry out essential metabolic processes which the hosts cannot carry out by themselves, for example, cellulose degradation in ruminants, essential amino acid synthesis in insects, and in case of humans, conversion of dietary fibre to the short-chain fatty acids- acetate, propionate, and butyrate. 

Up until recently, symbiont interactions have been most commonly studied in plants, like association of Rhizobia strains with legume plants; invertebrates, for example, the relationship between some species of squids and the bacterium Vibrio fisheri which triggers formation of the light organ in the squid, and other organisms exhibiting primary symbiosis. But recently, it has been shown that this kind of association occurs in case of higher plants and animals too. In vertebrates, for instance, the gut microbiome promotes the strengthening of immunity by initiating formation of memory B and T cells, and in development of body organs. It also aids in the development of bone mass and blood vessels in the intestinal walls. Bacteria in the mammalian gut are also thought to be associated with brain development and behaviour, including anxiety and mood disorders along with modulating serotonin levels.

What next?

As the Holobiome theory evolves, holobiont evolution too must be represented mathematically and a population genetics theory for it should be developed and efforts have been made to do just that. Differences in the manner of gene transfers within the microbiome and the host, holobiont and coevolutionary selection, the genetics of hologenotypes, and multilevel fitness for microbes, are some of the factors needed to be considered while developing an algorithm. As a holobiont comprises many different populations each contributing to its evolution uniquely, it is no small task to account for all the systems, their nuances, and the variables they create while deducing new theoretical concepts and deriving mathematical expressions for them. As Raphael Kellman once wrote, “As soon as we pass through the birth canal, we begin to become 90 percent microbe.” We are the ecosystem for the microbes inhabiting us, and this thought is at once breathtaking and unnerving.

Reference (Apr-21-A6)

About the Author
I am a first year MSc. Biochemistry student at University of Hyderabad. I wish to pursue a career in the field of computational biology. I am currently training in data analysis and studying the differential gene expression in human brain cells at various stages of life by performing transcriptome analysis.


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