Category Archives: Hologenome

Viral Metagenomic Studies

Viral MetagenomicsViral genomics is the study of the full composition of viral genetic source material in the environment. Studies utilizing new technologies are identifying an enormous range of viral diversity that is typically invisible to standard studies. The hologenomic participants in an ecology cannot be fully understood unless these entities are identified. The metagenomic approach has improved our understanding of viral epidemiology, the impact of viruses on our evolutionary transit and has impacted and accelerated the discovery of previously unsuspected viral participants.

Part of the difficulty in identifying viral strains is that many viruses are difficult to amplify in cell cultures. However, there are now numerous molecular techniques to genetically characterize and identify new viruses without the limitations of prior techniques requiring targeted reagents. The range of ecologies to which these new techniques have been applied is quite far reaching. For example, seawater, feces, shore sediments, plasma, or respiratory secretions are only a few. The product of these investigations is a new understanding of the profound variety and influences of viral loads on every ecology. 

Among other things learned to date, unbiased characterization of viral loads on various populations is challenging our prior notions of ‘sterile’ environments. Such studies need not apply to just viral load however. In 2013, a new species of bacteria was discovered in the ‘clean’ rooms used by NASA to build their spacecraft. It had been previously assumed that these specialized rooms were sterile. However, as it has been discovered, this was an unwarranted assumption. In 2007, an unusual bacterium was identified that had eluded all known and repeated sterilization methods. Two years later, this same bacterium was identified inside a clean room at the European Space Agency’s launch site in South America, nearly 2500 miles distant from the site at which it was first discovered. Analysis showed that it should be considered not only a new species, but also an entirely new bacterial genus with a unique molecular composition of its cell wall and other differentiating properties. 

Metagenomic studies based on new techniques beyond outdated cell culture methods allow researchers to identify a wide variety of microbial life that has been hidden from our purview. Some of this previously invisible life as already hitched a ride to any place in space that we have attempted to explore. Surely this is unintentional, but the implications are as yet unknown. 

Hologenomic evolution theory asserts that all multicellular organisms are highly complex and largely specific united co-dependent ecologies. We are only now beginning to understand how profound and varied this partnership can be. As abundantly documented in The Microcosm Within, we are all the current products of hologenomic forces that are only just beginning to be comprehended through the new types of investigations, such as metagenomic analysis, that are only now commonly employed.

Metagenomic Assembly

Metagenomic evaluation of any environment, ecology or tissue sample requires extensive computational power in order to properly assess large volumes of sequence data. This is required to mobilize an accurate representation of genetic diversity in a sample. New techniques in de novo metagenomic assembly effectively filter the total amount of data to be analyzed; yet, vast amounts of computer power are still required. New approaches to that analysis and changes in
the filtering methods have enabled improved methods of metagenome assembly of a more accurate characterization of the full range of microbial life in a sample. Complex software is necessary since in conventional genome analysis, only one species is being analyzed. However, metagenomic sample analysis, the required metagenome assemblers use algorithms to additionally separate species and to also attempt to assess their relative abundance. Different assemblers, utilizing differing techniques, can skew results based on scalability of the software and variability in data reconstruction filtering techniques. Recent studies have attempted to demonstrate that filtering shortcuts can still permit accurate analysis of any sample.

For example, the exact composition of the microbial life in any given sample surely contains mixed populations, but the exact species and the relative abundance of them are unknown. When standard metagenomic analysis is applied (shotgun sequencing), there is disruption of the sequencing data and grouping by species can be very difficult. Newer techniques are permitting more accurate analysis through chromatin level probability maps so that the individual genomes of microbial species can be accurately reconstructed within a mixed sample. 

The validity of some of the short cut techniques employed by metagenomic assemblers is typically assessed against published references of current metagenomic data. One problem is that the full complement of microbial life for any sample, for example, the human gut is still not fully understood. Metagenomics is only in its initial phases and surprises are revealed routinely in the analysis of tissue and environmental samples. 

For example, very recent evaluation of the human gut metagenome revealed a previously unknown gut virus, which has been linked to human chronic disease. Researchers indicate that this virus, called Assphage, lives in the gut of more than half of the world’s population and infects a common gut bacteria, Bacteroidetes. This particular virus was identified through a computer program and had not been previously identified. Yet it is ubiquitous and is currently believed to have a major role in diabetes and obesity. So at this moment, exciting new technologies are deepening our understanding of ourselves as the complex linkages of co-dependent ecologies outlined in The Microcosm Within. Metagenomic assembly is one tool to assess that partnership. Yet, there will be many surprises along the path to our fuller understanding of the power of those associations. 

Books on Evolution

It is surprising how few people have actually ever read Darwin’s On the Origin of Species by the Means of Natural Selection (1859) since it is referenced abundantly and considered a foundational event in evolutionary biology.
It is not surprising then that it is generally unappreciated that Darwin did not actually answer the specific question of exactly how species arise. Instead, he proposed that evolutionary development proceeds through differential reproductive success, through competitive natural selection and also championed the concept of descent by gradual modification. But, there is a long list of scientists that have offered credible and thought provoking books to further explain evolutionary development and speciation and many of these were critical to the construction of the ideas underlying of The Microcosm Within.

Which sources might an interested person read in order to get a general background in the history of evolutionary thought? Certainly, skipping towards the present day makes the most sense. Interested individuals should consider becoming familiar with some of the works by Stephen Jay Gould. For example, his Wonderful Life: The Burgess Shale and the Nature of History (1989) is beautifully written and examines the critical Cambrian explosion and other discontinuities in evolutionary development. The works of Richard Dawkins [e.g. The Selfish Gene (1976)] are thought provoking and are useful in an historical sense. Much of what is currently written is a reaction to his critical thinking.

Acquiring Genomes: A Theory of the Origins of Species (2002) by Lynn Margulis and Dorion Sagan represented a radical rethinking of evolutionary biology with their championing of symbiogenesis. This courageous departure from mainstream thought remains a powerful influence in evolutionary biology.

Sean Carroll in Endless Forms Most Beautiful (2005) lucidly explains the newer concepts of evo-devo, particularly how HOX genes serve conservation of forms.

For those interested in an informative critique of Neo-Darwinism, What Darwin Got Wrong (2010) by Fodor and Piattelli-Palmarini offers a trenchant review of its inadequacies. Speciation (2004) by Coyne and Orr gives an excellent capsule background into modern concepts in speciation. Fox and Wolf, in Evolutionary Genetics (2006) do the same for gaining an initial grounding in genetics. In The Plausibility of Life (2005), Gerhart and Kirschner offer an elegant attempt to find some means for accounting for the failures of the Modern Synthesis through concepts of facilitated variation. Their struggle to offer satisfactory answers, just like Dawkins, is pertinent to our ongoing debate.

Arguably, the best of the current works is the thin volume by James Shapiro, Evolution: A View from the 21st Century (2011). His concepts of natural genetic engineering, which are wholly part of hologenomic evolution theory, are explained in careful and rich detail.

All of these sources have been critical to the formulation of hologenomic evolutionary theory and I consider myself indebted to all of them. Each has contributed brilliantly to a field in which there is never final truth.

Microbiomes and Their Role in Evolution Biology

There are currently estimated to be at least 100 trillion microbes that are in and on us — bacteria, viruses, fungi and others. They outnumber our innate cells by a factor of 10 to 1 or more. We cannot do without many of them for proper function of our brains, gut, central nervous and immune systems.They cannot exist as they want without us.

Some researchers have begun to view organisms as multi-species units but remain constrained by retaining an outmoded model of ‘host’ and ‘guest’ with respect to those interacting species. However, instead of viewing organisms as inherent singularities or even as a group of linked singularities, it is more accurate to regard organisms as united vast collaborative enterprises. These consist of a co-linked, cooperative, co-dependent and competitive ecological community of microbiomes merged together so seamlessly that they seem, at least to the consciousness of any particular organism, as one discrete entity. In this model, there is no simple or absolute ‘host’ and ‘guest’ as all function reciprocally to make the effective whole. In this conception, it is the specific collection of such linked ecological communities that makes each species unique. Any complex organism itself represents an entire ecology reiteratively constructed from all of the relevant smaller ecologies that make it so. That larger coalesced ecological unit then has its own exquisite place within the larger external environmental ecologies. Each ecology and all the linked ecologies remain together and function with purpose to sustain the individual constituent cells that make up each ecology. So at every time, the linked ecologies that make an organism such as ourselves are working to maintain the preferred status of their constituents’ cells. To serve those needs, they remain separably discriminative in their range of responses. Those specialized responses serve the whole. Yet, they are so harmoniously associated together as to seem to the organism itself as though they are one.

There would be no requirement that all of the exact constituents of the conjoined ecologies that make an organism stay static. Indeed, we know that they do not. However they do need to stay within biological boundaries or that exact species forfeits its place in a competitive landscape in which any organism is under continuous assault by a very aggressive external genetic milieu. This is the exact interface between health and disease for all complex creatures. 

If this seems a bit daunting, it is so only at first blush. Nature certainly does not see us as singularities as the Darwinist have long believed. Instead, we are holobionts. There is no pore, orifice or hidden compartment within us that is ‘sterile’. That concept is now defunct. Importantly though, it is not that just some complex organisms are hologenomic beings. All complex organisms are, and there are no exceptions on this planet. So any coherent theory of evolutionary development must endorse that endpoint as its narrative. 

Neo-Darwinism and Modern Evolutionary Synthesis

It is not well recognized that Darwin in his book On the Origin of Species did not specifically explain how a species originates but discussed how an organism became fitter and better adapted gradually over time. Even during his lifetime, others pointed out the problem of dilution of favorable traits by blending within the reproductive population. George Romanes, one of Darwin’s academic friends, emphasized variation in reproductive ability as a source of new species and coined the term Neo-Darwinism. From that time forward and through successive iterations, the core concept of Neo-Darwinism has remained rooted in variation. Natural selection drives evolution based on that variation. In a modern context, that variation is produced by genetic mutation and genetic recombination.
Despite vigorous discussion, Darwin’s theories did not really gain widespread acceptance until the 1930s and 1940s with the formulation of the Modern Evolutionary Synthesis (Neo-Darwinism). This was the unification of Darwin’s ideas with those of Mendelian genetics. This widely accepted theory holds that genetic variation arises by chance through random genetic mutation with evolution consisting primarily of changes in the frequency of alleles (any one of a number of alternative forms of the same gene) between one generation and another. The consistent attempt to reconcile Mendelian genetics with the introduction of new species has been an important feature of the debate.