Articles & Reviews
Authored by RSF Research Staff
The Living Universe
Ubiquitous Biogenesis and Transposon Engineering of the Human Genome:
The question is often asked - "how did life originate?" however, the question is posed within the narrowly defined framework of how life originated on Earth, and while this is a highly interesting topic of discussion, it may facilitate our investigation to understand that living systems originate from living processes within a living Universe. So the emergence of biological organisms on Earth is not the origin of life per se, which is to say that we may be able to identify living processes of pre-biotic molecules occurring nearly ubiquitously, for instance in the formation and dissolution of stellar systems. However, there are certain insights that can be gleamed from our knowledge of the nanomolecular machinery that comprises the extant biological system that can address the actual mechanism of the processes by which organisms may have come to inhabit the Earth. Specifically, the evolutionary pathway of the DNA-mRNA-tRNA/rRNA transcription and translation system, which is the information system at the heart of all biology, emphasizes the gap in the description between the observed extant complexity and the putative processes that would have fostered, or even driven, the emergence of such complexity.
Furthermore, we know from phylogenetic studies that the rRNA molecule (see videos below for more information on the ribosome), specifically the 16S subunit, has remained relatively unchanged since the earliest inception of life, as all three domains of life, Eukarya, Prokarya, and Archea – even mitochondria and chloroplasts - have highly conserved motifs of the rRNA genes. Considering that life was on Earth up to 4 billion years ago (4 GYA, approximately 300 million years after the surface cooled from a molten state, marking the transition from the Hadean to the Archean eon) and contained microbial communities by 3.48 Ga resembling those extant today; it is highly unlikely that the extremely complex machinery of the DNA-mRNA-tRNA/rRNA system evolved within the relatively short time span in which life emerged on Earth, strongly indicating an extrasolar origenesis of prebiotic, or biological molecules.
Over the past two decades substantial progress has been made in delineating the structure and function of three key molecules within the biological system:
These are nanomolecular machines with great complexity and astonishing functionality. Presumptively, they evolved prior to the emergence of Eukaryotes an estimated 2.5 billion years ago because they are observed in Prokaryotic, Eukaryotic, and Archea species. Therefore they were present in the last universal common ancestor (LUCA), which is derived from the first organisms to inhabit Earth some 3.5 billion years ago.
The discrepancy that becomes apparent when considering all of this together regards the temporal relationship between these evolutionary landmarks. If it took one billion years for cells to form endogenous membrane-bound organelles, and 0.5 billion years to form the molecular apparatus needed for cell-to-cell adhesion and communication, these are relatively simple macromolecular structures compared to the Ribosome and Polymerase nanomachinery, which would have had to evolve astonighingly rapidly, within a couple hundred million years -- a situation which is difficult to reconcile with logic.
Gap and adherence junctions are important structural elements in forming multicellular assemblies. In the image below, the pathways of synthesis and assembly of gap junctions and all the respective protein elements (the gap junction proteome) are depicted. Like most sub-systems within the biological organism, it is a complex affair -- yet the structural and functional complexity of gap junctions are relatively simplistic as compared to the multi-complex polymerase machinery (outlined in the videos above). Why would it take approximately one billion years to form this multicellular arrangement, while the polymerase machinery is formed in an astonishingly short 200 million year period (ostensibly)?
Given that fossilized evidence indicates that it took around one billion years to form the relatively simple molecular machinery needed for subcellular organelles - it is perhaps logical to posit that it would have taken a considerably longer amount of time for the evolutionary process to produce the highly complex and sophisticated Ribosome and Polymerase enzymes. Especially given that these nanomolecular biomachines evolved from considerably more simplistic RNA enzymes known as Ribozymes (ostensibly).
This means that the cellular system would have had to convert from an RNA-based replication process to a DNA-based RNA-protein complex replicative mechanism in an astonishingly short interval of time - considering the staggering amount of serendipitous random mutations that would be necessitated to do so (following a stochastic model of accidental evolution, which we will investigate in more detail in later discussions).
It is therefore quite possible, and logical, that the first organisms arrived on Earth with this replicative machinery intact and fully functional. Whereby there would have been an initial development of life that involved several billions of years to develop the machinery needed to switch to a DNA-based system and to decode that information to form proteins. In this way the evolution of life would parallel the evolution of the Universe itself. In that prebiotic processes began shortly after enough heavy nuclei were produced to form organic compounds in the nebulae from which solar systems and planetary bodies coalesce.
Following this model, the origenesis of life occurred before the formation of Earth and seeded newly forming planets through an interstellar dispersal. Meaning that life is universal and that the entire galaxy may share a common universal ancestor through the process of Panspermia.
Indeed, it was Sir Francis Watson Crick's investigations into the decoding of information from the DNA molecule via the mRNA and tRNA pathways that led him to posit a theory of Directed Panspermia. He discussed this in detail in his book Life Itself, which is perhaps one of the first scientific treatises on Exobiology.
The Living Matrix
When we consider the ultimate nature of life and living systems, the key characteristic - indeed the defining characteristic - is the demonstration of intelligent behavior. Therefore we can say that life exhibits intelligence. Now, keeping this in mind, we take into consideration some of the most advanced cosmological models, in which the Universe is described as ultimately holographic and fractal - and we can begin to understand how such complex nanobiological machinery could be engendered, using a more accurate model than what was available to Darwin when he formulated his theory of blind evolution through random mutagenesis.
In the holofractal model of cosmology, information is encoded in the quantum structure of spacetime.
This information is encoded at the most fundamental level, in the quantum vacuum harmonic oscillators, or planck pixels, that comprise the very fabric of the spacetime manifold itself. As the saying goes - "it from bit", meaning that all parameters of physical processes are encoded digitally (discretely) as information topologically on holographic spacetime surface horizon membranes.Furthermore, within this model the Universe is not only holographic, in which the smallest unit of a system recapitulates the whole, but also fractal, in which it is self-similar across scales.
When the fractal Mandelbrot set was first discovered, it was described as "God's fingerprint". We are all very familiar with fractal systems as they are displayed by almost all living processes and structures - suggesting that fractal processes are integral to the morphogenetic field of the living biological system. However, the fractal arrangement of the Universe can be seen from the largest scales to the smallest -
Some of the astonishing arrays of holofractal arrangements seen throughout the Universe are detailed in the following video (the term fractal ultimately being a mathematical description, which includes geometries such as the Fibonacci sequence).
Now we can begin to define what is meant by the statement - "living processes do not come from non-living processes". Because in a holofractal universe, the macromolecular arrangement and behavior of matter demonstrated in biological life forms is recapitulated through all scales, even if we choose not to recognize it as such. Thus, what is termed to be living is not simply something that looks like an organic life form - but something that is inherently intelligent and demonstrates a clear ordering of action and behavior.
When considering the information transduction processes occuring from the smallest scales to the largest, it is important to point out that biological life forms fall right in the equiposition between the Planck-scale and the cosmological-scale:
There are 30 orders of magnitude on either side of the living biological system, meaning that there is an entire universe within the living organism at the same magnitude as that outside the living biological entity. Poised at this equiposition, living biological systems are the key intermediary in the communication of information between these extreme scales.
Now considering this holonomic fractal model, there are living processes all the way from the harmonic oscillations of the quantum vacuum to the large-scale Universe, and given that all physical processes are the result of underlying information transmission, permutation, and encoding, there is an intelligence engendered within all physical processes.
When considering the intricate and intimate matrix that extends through all scales and spacetime dimensions, the synergetic effect of these information transduction processes, of which life is literally central to, could potentially engender a unified intelligence, perhaps great enough to reach back across that spacetime manifold to orchestrate the design and emergence of biological life - an expression of living systems that would ultimately display higher-order sentience by that design.
Transposon Engineering of the Human Genome
“It could be that at some earlier time somewhere in the Universe a civilization evolved by probably some kind of Darwinian means to a very high level of technology and designed a form of life that they seeded onto perhaps this planet. Now that is a possibility, and a very intriguing possibility. And I suppose it’s possible that you might find evidence for that if you look at the details of biochemistry and molecular biology, you might find the signature of some sort of designer… and that designer could well be a higher intelligence from elsewhere in the Universe, but that higher intelligence would itself have had to come about by some explicable or ultimately explicable process…” Richard Dawkins.
The Alu element has been instrumental in the development of the human species. This non-protein coding gene sequence has neural specific functions and seems to be specific to the hominid lineage. Fascinatingly, an Alu retrotransposition into the CMP-N-acetylneuraminic acid (CMP-Neu5Ac) hydroxylase (CMAH) gene occurred prior to the enlargement of the human brain, and could very well have been a key event in the molecular evolution initiating brain expansion in the human lineage -
Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution
Inactivated Alu elements are found within other primates and this may be due to lateral gene transfer, because it is largely inactive within all other primates except for humans. This conjecture is also based on an alternative paradigm for non-coding transposable sequences – which have been described within popular theories as “Selfish DNA”. This is from the opinion that the sequences confer no selective advantage to the organism and function only to expand within the genome at the expense of the “host” organism. This has been shown to be erroneous as Alu ncRNAs (non-coding ribonucleic acids) have very defined functions in regulating gene expression from nucleolar hyperediting of mRNA transcripts to translational regulation at the Ribosome complex1, 2.
Even with the paucity of fossil remains for data on the human evolutionary history, it is nevertheless evident that human evolution is characterized by punctuated speciation and adaptation, in other words, the human lineage emerged extremely rapidly, in evolutionary terms. This has left evolutionary biologists scrambling for a coherent theory that can supplant the normal Darwinian postulation of a gradual, incremental progression of emergence of traits and human characteristics. I believe one thing is for certain, the insertion of retroviral elements, such as the Alu element, was a major impetus for the rapid evolution of the human lineage. While this is within the scope of a natural evolutionary pathway, like so much of the human evolutionary history, there are a great deal of unanswered questions remaining, specifically regarding the mechanisms by which this occur.
Altruistic versus selfish DNA - the genetic web of life
The very same DNA that is commonly labeled as selfish I refer to as “Altruistic DNA”. It confers selective advantages to the organism through a variety of functions and is evidence of past molecular altruism – i.e. intra and interspecies gene-sharing (http://www.scienceagogo.com/news/20070029220033data_trunc_sys.shtml). This allowed for the sharing of beneficial and useful genes – and may even be the explanation for the origin of viruses – as a molecular mechanism for organisms to share novel alleles and beneficial genes, but which overtime through the processes of evolution produced variants that replicated at the expense of the host. There still could be viruses that do nothing more than swap gene-segments, but we wouldn’t necessarily know they were there or active, because we are only aware of the other variants when they produce a diseased-state, and even then we don’t always successfully identify them as the etiological agent.
In discussing the nature of gene-sharing Dr. Peter Gogarten’s perspective was duly noted:
In this very same discussion something else very pertinent is noted:
This is pertinent because it brings to light the topic of panspermia, which is also alluded to in Richard Dawkins comment above. Panspermia is the theory of an extraterrestrial genesis of life, usually taken to be a passive “diffusion” like event through space, but can also include directed panspermia. If it were to be the case it would mean that life within this sector of the galaxy (or possibly beyond) would share a common origin and therefore have the same elemental constituents – a universal life code. This would also be very harmonious with the observation raised by many that the Universe seems particularly fine-tuned to produce and sustain the condition known as life – it is a living Universe.
To what degree intelligent design is conceived as a possible explanation for origenesis depends upon whether intelligence and life is viewed as an epiphenomenon of matter or as being the substratum of the Universe itself. I believe that intelligence is present at every level of reality, and evolution therefore is an intelligently driven process. This is a much more expansive view of intelligent design than the very limited scope that is conventionally offered, because it means that the organism itself can be its own intelligent designer. Again I will use Dr. Gogarten to elucidate this perspective:
Directed evolution can extend from the molecular level to the organismal. Considering the perspective that this is a living Universe - then life is ubiquitous. And being explicitly driven to produce life, then over the course of 15 billion years many life-forms have arisen all over the Universe - and even if only probabilistically, some of them are going to be higher cognitively functioning organisms. If a sufficiently technologically advanced species were to evolve they could certainly engineer other life forms, and as Richard Dawkins pointed out, there could very well be evidence of exactly this circumstance taking place.
And it is the Alu element which I believe may demonstrate evidence of directed molecular engineering to produce higher cognitively functioning species, specifically of the primate lineage. It has been shown to be especially active and functional within the human genome, with a high degree of localization and activity within the human brain (see below). The Alu element is derived from the 7SL RNA component of the Signal Recognition Particle apparatus. However there are structural and sequence motifs of the Alu element that are not found within the 7SL gene, and their deliberate placement within the Alu locus means that they were most likely not acquired randomly by gene-fusion events.
Understanding the nature of the origins of humanity is pertinent because it informs us of the nature of humanity itself. While the prevailing scientific theory of Darwinian evolution presents the question as being almost entirely delineated except for some minor details, there are in fact major discrepancies between the prevalent explanation and the molecular evidence (See here for a more detailed presentation). The Darwinian theory of evolution posits that speciation occurs by the accumulation of random mutations in genes that over the course of millions of years results in beneficial traits that are selectively adaptive. It takes millions of years for a beneficial isoform to emerge because random mutations are almost entirely negative or neutral in effectuation. Currently within the consensus paradigm protein-coding genes are thought to be the only portion of the genetic material that produces physical traits.
So the speciation of humans would occur over the course of millions of years with the accumulation of random mutations within the protein-coding segments of an ancestral primate, which would eventually be sufficient enough that the progeny would be a new species, and selective pressures (primarily of the environment) would select those mutated isomorphic genes (alleles) that produce human traits, which would have to be the most adaptive traits for survival in that environment. In this sense the emergence of the human species would be entirely the consequence of an environment that happened to favor the behaviors and morphological characteristics of that form – blindly and completely by accident - it was just a serendipitous happenstance of the environment to favor human-like characteristics.
The chimpanzee is considered the closest phylogenetic relative to humans, meaning that during the evolution of our species the most recent bifurcation from the primate ancestor was between the human and chimpanzee lineages (William Brown, 2009). With the sequencing of both the human and chimpanzee genomes a comparative analysis of protein-coding sequences shows an approximate 98-99% similar sequence identity, or homology. The value is approximate because there can be more difference in the protein-coding sequences between two humans than between one of those same humans and a chimpanzee, and the same holds for the comparison of two chimpanzees, such that the difference is dependent on which individuals are being compared.
A 1.5% difference in protein-coding sequences is not sufficient to generate the differences observed between the two species on its own accord. Therefore, the difference in the species must be from the non-coding sequences of the genome. These non-coding sequences could regulate the expression of the protein-coding genes and therefore function to increase their functionality, or produce novel functions by altering their spatiotemporal expression. Even the mechanism of alternative splicing could function to expand the repertoire of functional isoforms, such that cumulatively the ~1.5% could be a functional difference of 5-10%.
However the molecular evidence (structural and architectural analysis and comparison of the genome) indicates that the actual mechanism primarily responsible for speciation was genomic remodeling through chromosomal re-arrangements3 (http://www.scienceagogo.com/news/20030205170948data_trunc_sys.shtml). This has been demonstrated to produce rapid speciation without any sequence changes in the DNA itself. Indeed it has been verified that inversions, deletions, and insertions are the major architectural motifs that characterize genomic differences between humans and other Great Apes. Now the question arises, by what manner are chromosomal re-arrangements induced? And the answer again is the non-coding DNA, specifically the mobile genetic elements referred to technically as transposons.
The transposable elements not only affect the re-ordering of chromatin modules within the genome to produce new species, but they also function epigenetically and transcriptionally within the organism. Within the human-lineage there is a very specific retrotransposon known as the Alu Element. It is the most prevalent element within the human genome, with a copy number of over a million loci, that’s 10% of the human genome, and it has expressed RNA isoforms that function in post-transcriptional gene regulation and protein function.
Alu elements are non-randomly distributed through the genome4! In fact they are used to selectively isolate gene-coding regions because they are preferentially located in the 5’ gene-regulatory regions of the genome! There are many subfamilies of Alu element isoforms that are specific to the Human genome5. The active retrotransposition of Alu elements in somatic tissues has been implicated in shaping the human brain6:
Alu elements are derived from an ancestral 7sl gene, which itself is an RNA component of the Signal Recognition Particle apparatus that translocates nascent proteins into the endoplasmic reticulum. However the Alu element has several characteristics that are not found within the 7sl gene, and taken together with its unique role within human biology, it strongly supports the supposition that this element was intelligently engineered. The Alu element has insertion sequences that were not acquired from the 7sl gene as well as a unique terminator sequence associated with these repeat sequences7. These sequence motifs are highly important to the expression and translocation of Alu elements, and given the high degree of functionality – such as specific insertion into gene rich regions – it is suggestive that it is not the result of spontaneous generation or a happenstance of gene fusion but intelligent design. Even more surprisingly – Alu sequences contain Retinoic Acid Response Elements8! Retinoic acid is a signaling molecule that is involved in development, and cellular differentiation.
Retinoic acid receptors are transcriptional regulators important in many cellular functions. From a molecular engineering perspective this is highly suggestive because when a foreign gene is inserted into a host, one of the mechanisms to drive the expression of the ectopic gene is to create a hyperactive promoter in the 5' region. What is very similar and slightly more sophisticated, in that the transcriptional promoter element is highly responsive to developmental conditions - just what would be needed to alter or modulate the developmental pathway of a given tissue.
There are also indications of intelligent engineering from structural motifs of the Alu RNA molecule. One of the Alu isoforms is a dimer (that is two Alu monomers bonded together) and the way the dimer is stabilized (that is brought into association for bonding) is through a linker sequence (Figure 2). How did this linker sequence arise to stabilize formation of the tertiary structure of the Alu ncRNA (Figure 3)? Within modern day molecular engineering this is the exact technique used to produce dimers of fusion proteins! A linker sequence will be inserted into the transcribed region of the cloned DNA sequence to keep the two protein domains in close association after translation so that they form intermolecular bonds and dimerize - just like what is seen in the Alu element!
To further support the hypothesis that Alu elements are key molecules in the evolutionary development of humans and in producing higher cognitive abilities we will examine the BC200 Alu-like RNA. BC200 is a human-specific cytoplasmically expressed element of the Alu family retrotransposons. It is one of the only transcriptionally active Alu sequences within the human genome and its expression is localized specifically to the neural tissue. As seen in the caption taken from Martigenetti’s and Brosius’ paper the gene is functionally active in the human brain and confers a selective advantage to the species.
In Summation, life is synonymous with existence and is eternal, and the most fundamental fabric of reality is consciousness. It is a Field of pure abstraction and intent, and through self-interaction it produces manifestations from endless potentialities. Therefore the Universe itself is intelligent, and this reality construct is the result of intelligent design. Every aspect is intelligently designed and contains consciousness itself. This does not mean it is a controlling factor and that there isn’t randomness, because the spirit of free will is intrinsic. Indeed the process of randomness is a testament to the sublime intelligence of Cosmic Consciousness. In that a system can be allowed to evolve completely independently – and yet the state of each constituent of the system is known at all times and the behavior upon the addition of a particular influence can be precisely predicted. However this terminology is misleading, because it indicates that the system would be outside of and apart from the Intelligence, when in fact it is an aspect itself of the Unified Consciousness – as everything is truly One.
By: William Brown
- Julien Ha¨sler and Katharina Strub. Alu RNP and Alu RNA regulate translation initiation in vitro. Nucleic Acids Research, 2006, Vol. 34, No. 8 doi:10.1093/nar/gkl246
- Ling-Ling Chen, Joshua N DeCerbo and Gordon G Carmichael. Alu element-mediated gene silencing. The EMBO Journal (2008) 27, 1694–1705 | & 2008 European Molecular Biology Organization
- Farre´ M, Bosch M, Lo´ pez-Gira´ldez F, Ponsa` M, Ruiz-Herrera A (2011) Assessing the Role of Tandem Repeats in Shaping the Genomic Architecture of Great Apes. PLoS ONE 6(11): e27239. doi:10.1371/journal.pone.0027239 Editor: David Liberles, University of Wyoming, United States of America.
- Cooper, David N., Dr. Human Gene Evolution. Oxford : Bios ; San Diego, CA : Distributed in the U.S. and Canada by Academic Press, 1999.
- Mark A. Batzer, Prescott L. Deininger. A human-specific subfamily of Alu sequences. Genomics. Volume 9, Issue 3, March 1991, Pages 481–487.
- J. Kenneth Baillie. Somatic retrotransposition alters the genetic landscape of the human brain. Nature, Letter. 2011.
- Wen-Ming Chu, Ruth E. Ballard and Carl W. Schmid. Palindromic sequences preceding the terminator increase polymerase III template activity.Nucleic Acids Research, 1997, Vol. 25, No. 11 2077–2082.
- Gordon Vansantr Ad Wanda F. Reynolds. The consensus sequence of a major Alu subfamily contains a functional retinoic acid response element. Proc. Natl. Acad. Sci. USA, Vol. 92, pp. 8229-8233, August 1995. Biochemistry.