Eugene Rosenberg

The composition of bacteria in the human colon has been a subject of interest since the beginning of microbiology. With the development of methods for culturing strict anaerobic bacteria under multiple culture conditions, it was shown the gut contained more than 400 bacterial species and different people harbor different abundant species. The term “gut microbiome” in this review refers to bacteria studied in stool samples. Molecular methods for determining the bacterial composition of human gut has revealed more than 3000 species and less than 130 genera, indicating that the diversity of human colonic bacteria is concentrated at the species and strain levels. This review concludes with a discussion of how diversity can lead to unity of individual holobionts, between holobionts, and between populations. One of the reasons for the unity is that different bacterial species can have similar functional genes.

The punctuated mode of evolution posits that evolution occurs in rare bursts of rapid evolutionary change followed by long periods of genetic stability (stasis). The accepted cause for the rapid changes in punctuated evolution is special ecological circumstances – selection forces brought about by changes in the environment. This article presents a complementary explanation for punctuated evolution by the rapid formation of genetic variants in animals and plants by the acquisition of microorganisms from the environment into microbiomes and microbial genes into host genomes by horizontal gene transfer. Several examples of major evolutionary events driven by microorganisms are discussed, including the formation of the first eukaryotic cell, the ability of some animals to digest cellulose and other plant cell-wall complex polysaccharides, dynamics of root system architecture, and the formation of placental mammals. These changes by cooperation were quantum leaps in the evolutionary development of complex bilolgical systems and can contribute to an understanding of the mechanisms underlying punctuated evolution.

It is now well established that all animals and plants harbor abundant and diverse microorganisms, including bacteria, archaea, viruses, and eukaryotic microorganisms

Microbiomes are transmitted between generations by a variety of different vertical and/or horizontal modes, including vegetative reproduction (vertical), via female germ cells (vertical), coprophagy and regurgitation (vertical and horizontal), physical contact starting at birth (vertical and horizontal), breast-feeding (vertical), and via the environment (horizontal). Analyses of vertical transmission can result in false negatives (failure to detect rare microbes) and false positives (strain variants). In humans, offspring receive most of their initial gut microbiota vertically from mothers during birth, via breast-feeding and close contact. Horizontal transmission is common in marine organisms and involves selectivity in determining which environmental microbes can colonize the organism’s microbiome. The following arguments are put forth concerning accurate microbial transmission: First, the transmission may be of functions, not necessarily of species; second, horizontal transmission may be as accurate as vertical transmission; third, detection techniques may fail to detect rare microbes; lastly, microbiomes develop and reach maturity with their hosts. In spite of the great variation in means of transmission discussed in this paper, microbiomes and their functions are transferred from one generation of holobionts to the next with fidelity. This provides a strong basis for each holobiont to be considered a unique biological entity and a level of selection in evolution, largely maintaining the uniqueness of the entity and conserving the species from one generation to the next.

Genetic variation in holobionts (host and microbiome), occurring in both host and microbiome genomes, can be observed from two perspectives: observable variations and processes that bring about the variation. Observable includes the enormous genetic diversity of prokaryotes, which gave rise to eukaryotes. Holobionts then evolved a rich microbiome with a stable core containing essential genes, less so common taxa and a more diverse non-core, enabling considerable genetic variation. Thus, the human gut microbiome, for example, contains 1000 times more unique genes than are present in the human genome. Microbial-driven genetic variation processes in holobionts include: (1) acquisition of novel microbes from the environment, (2) amplification/reduction of certain microbes in the microbiome, (3) horizontal gene transfer between microbes and between microbes and host and (4) mutation, which plays a role in optimizing interactions between microbiota and between microbiota and host. We suggest that invertebrates and plants, where microbes can live intracellularly, have a greater chance of genetic exchange between microbiota and host, a greater chance of vertical transmission and a greater effect of microbiome on evolution than vertebrates. However, even in vertebrates the microbiome can aid in environmental fluctuations by amplification/reduction and by acquisition of novel microorganisms.

All natural animals and plants are holobionts, consisting of the host and microbiome, which is composed of abundant and diverse microorganisms. Health and disease of holobionts depend as much on interactions between host and microbiome and within the microbiome, as on interactions between organs and body parts of the host. Recent evidence indicates that a significant fraction of the microbiome is transferred by a variety of mechanisms from parent to offspring for many generations. Genetic variation in holobionts can occur in the microbiome as well as in the host genome, and it occurs more rapidly and by more mechanisms in genomes of microbiomes than in host genomes (e.g. via acquisition of novel microbes and horizontal gene transfer of microbial genes into host chromosomes). Evidence discussed in this review supports the concept that holobionts with their hologenomes can be considered levels of selection in evolution. Though changes in the microbiome can lead to evolution of the holobiont, it can also lead to dysbiosis and diseases (e.g. obesity, diarrhea, inflammatory bowel disease, and autism). In practice, the possibility of manipulating microbiomes offers the potential to prevent and cure diseases.

The holobiont (host with its endocellular and extracellular microbiome) can function as a distinct biological entity, an additional organismal level to the ones previously considered, on which natural selection operates. The holobiont can function as a whole: anatomically, metabolically, immunologically, developmentally, and during evolution. Consideration of the holobiont with its hologenome as an independent level of selection in evolution has led to a better understanding of underappreciated modes of genetic variation and evolution. The hologenome is comprised of two complimentary parts: host and microbiome genomes. Changes in either genome can result in variations that can be selected for or against. The host genome is highly conserved, and genetic changes within it occur slowly, whereas the microbiome genome is dynamic and can change rapidly in response to the environment by increasing or reducing particular microbes, by acquisition of novel microbes, by horizontal gene transfer, and by mutation. Recent experiments showing that microbiota can play an initial role in speciation have been suggested as an additional mode of enhancing evolution. Some of the genetic variations can be transferred to offspring by a variety of mechanisms. Strain-specific DNA analysis has shown that at least some of the microbiota can be maintained across hundreds of thousands of host generations, implying the existence of a microbial core. We argue that rapid changes in the microbiome genome could allow holobionts to adapt and survive under changing environmental conditions thus providing the time necessary for the host genome to adapt and evolve. As Darwin wrote, “It is not the strongest of the species that survives but the most adaptable”.