To the End of Dogmatism in Molecular Biology
Received: 27 February 2021 /Accepted: 17 March 2021/
#The Author(s), under exclusive licence to Springer Nature B.V. 2021
Denis Nobel looks at four important misinterpretations of molecular biology
concerning evolutionary processes and demonstrates that the new synthesis today looks
rather outdated. The modern synthesis is nearly 80 years old. The proponents who
worked out the modern synthesis had no access to the current knowledge on cell
biology, genetics, epigenetics, RNA biology and virology. Therefore this contribution
adds several aspects which Nobel’s article does not explicitly mention, providing some
examples for a better understanding of evolutionary novelty.
Keywords Dogmatism .RNA biology .Virosp here .Natural genomeediting .Mechanistic
Denis Noble’s Target Article is very attractive because it presents the list of mistakes in
the neo-Darwinian concept of the new synthesis. In an outline of thoughtful arguments
he presents the conceptual errors of the neo-Darwinian narrative of evolutionary
processes that represent a belief status hidden in empirically masked arguments.
Especially “natural selection,”“the Weisman Barrier,”“The Rejection of Darwin’s
Gemmules,”and the “Central Dogma”represent the four illusions of the modern
“Dogma”is a main assumption in religious beliefs designating that ultimate core
principles cannot be questioned because they are beyond doubt; that they need no
further rational justification or debate and serve as Archimedean point around which
several lines of logical argumentations are built. Similar to this the “central dogma of
molecular biology“describes the direction of information flow on the genetic level
from DNA to RNA to protein which is irreversible (Mattick 2009).
Telos-Philosophische Praxis, Buermoos, Austria
Noble’s argumentation does not touch the falsification of the old explanatory model
that error replications (mutations) are the driving force of genetic novelty. While he
rejects “gene-centrism,”he does not mention that all gene regulatory elements, which
are part of the genome also, represent both the driving force in evolutionary novelty and
an essential contradiction to the central dogma.
RNA World Agents
Single RNA stem loops react in a physical chemical way only. If multiple RNA stem
loops interact, biological selection starts (Vaidya et al. 2012). Out of an abundance of
RNA stem loop groups which constantly infected each other in competitive or coop-
erative interactions they built unlimited interconnections with larger groups stabilized
by protein structures.
Direct decendents out of these RNA stem loop groups are viruses which can be seen
in viroids consisting of RNA sequence structures only (Flores et al. 2014). Infectious
RNA agents that escaped out of a highly competitive RNA world by reverse transcrip-
tase (which is the original polymerase) into the stable DNA storage medium provided a
strong immune function against RNA infections at that time (Belfort et al. 2011).
Escape out of a highly competitive RNA world was reserved for such RNA nucleotide
sequences that have been transcribed into single stranded DNA which was
complemented by a second strand to form double stranded DNA. This we know as a
stable genetic information storage medium and the prevalent genetic heredity material
for cellular life (Gilbert 1986).
But the ancient RNA networks that predated cellular life are still present in an
abundance of RNA mediated processes without which cellular life cannot function
(Cech and Steitz 2014). We now know that cooperative consortia of RNA groups and
viruses or its “defectives”such as retroviral env, gag, pol or well investigated transpo-
sons, retrotransposons, long terminal repeats, non-long terminal repeats, long inter-
spersed nuclear elements, short interspersed nuclear elements, alu’s, group I introns,
group II introns, phages, and plasmids build highly dynamic networks that shape
genome structure of cellular host (Villarreal 2015). There is clear evidence that
evolution, conservation and plasticity of genetic identities of cellular host are the result
of cooperative consortia of RNA stem loops being able to use natural code and edit this
code. (Villarreal and Witzany 2015). Especially the ability to generate really new
sequences (not simply derivatives of previous ones) allows such groups constantly to
infect other nucleic sequence-based agents, whether virus-like or cellular genomes.
Viruses are the most abundant biological entities on this planet and outnumber cellular
organisms ten times. In one drop of seawater we find one million bacteria but ten
million viruses. If we think a lineup of all the viroids of this planet we reach a distance
of more than 43 million light years spanned by 1031 phage virions placed side-by side
(Rohwer et al. 2014). They represent a variety of genetic sequence structures not found
in any cellular organisms, which indicates they are older than cellular life (Koonin
2009). Viruses infect every cellular organism since the beginning of life. Most viruses
colonize host cells especially host genomes without harming the host. They remain in
most cases as defective viral parts such as mobile genetic elements that are coopted for
cellular needs and provide host organisms with all the known non-coding RNA
elements essential for gene regulation such as replication, transcription, translation,
repair and immunity in all detailed steps and substeps (Witzany 2011). If we look at
eukaryotic genomes we typically find this intron/exon division in genome architecture.
Whereas the introns have to be spliced out to reach an exon lineup for appropriate
translation into proteins, the remaining introns serve as regulatory networks with an
abundance of non-coding RNAs. This leads to a perspective of genomes as a certain
ecosphere and as rare resource and habitat for a tremendous number of infectious
genetic parasites (Villarreal and Witzany 2013).
Most importantly, several natural genome editing techniques have been found to change
the protein-meaning of given DNA such as epigenetic markings, alternative splicing, RNA
editing, pseudoknotting, alternative frameshifting, loop kissing, bypassing translation. All of
this coordinated processes modify the final protein result out of the transcription and
translation of a given genetic sequence syntax (Witzany 2020a). The DNA syntax remains
the same, while the modifying processes may change the meaning of this syntax according
pragmatic (context dependent) needs which derive from real-world circumstances, such as
environmental changes, conflict and/or cooperation activities or health problems (pain stress
and disease). Virus-derived elements we know as mobile genetic elements which insert and
delete, copy and paste, cut and paste within host genomes. Observing repetitive nucleotide
sequence structures always reminds us of RNA- world decendents, in contrast to non-
repetitive sequences which code for proteins (Witzany 2017).
Natural Genome Editing: Competent Modification of Genetic Texts
Non-coding RNAs and viruses shape the genome structure of cellular host organisms. It is
not the gene number which defines genetic identity of cellular organisms; e.g., C. elegans
and humans share approximately 20,000 genes. The genes of our closest relatives,
chimpanzees, differ only by 1,5%. Interestingly the genetic sequences that code for
proteins in humans compose only 1,5%, whereas the non-protein coding regions comprise
98,5% of the genome. Such findings clarify that the crucial biotic information at issue are
not the genes that code for proteins but the various steps and substeps of their regulation
by RNA- networks (Mattick 2003), as well as the regulatory elements of genes derived
from former infection events that are coopted for the regulatory purposes of the host
organism (Witzany 2009). This is not a mechanistic process, as suggested by the
mechanistic description “natural genetic engineering,”but it is natural genome editing,
like editing of a written text, this requires competent agents that act as networks and
groups to modify genetic sequences and avoid errors and damage (Witzany 2006a).
Mechanistic Error in the Twentieth Century
With the rise of molecular biology in the 20th century, understanding biology as a
subdiscipline of physics and chemistry was mainstream thinking. Main influencers at
To the End of Dogmatism in Molecular Biology
that time were physicists such as Erwin Schrödinger (e.g., life is physics and chemistry)
or even chemists like Manfred Eigen (e.g., the self-organization of matter). The
assumption that all living processes depend on mechanistic molecular and atomic
forces and features still dominates. Evolutionary novelty depends on variations in the
genetic heredity program and these variations in molecular structures could only under
this model be errors in replication processes.
But as we learned from RNA biology and the comeback of virology,
another perspective on RNA stem loop group behavior is more coherent with our
observations (Higgs and Lehman 2015). RNA stem loops have an inherent tendency to
build new sequences, new single stranded loops out of double stranded RNA stem
sequence. Such single stranded loops are prone to bind to foreign (non-self) single
stranded RNA loops to combine, to increase a group to form genetic group identities
which then can be inserted into host genomes by infection events (Hayden and Lehman
2006). RNA groups with a certain genetic identity may cooperate with other RNA
groups in building networks. We may identify such RNA groups that are conserved and
transfered into DNA storage medium of cellular host organisms. They must be
transcribed again back to RNA to become active agents in competent groups such as
e.g., the subunits of the ribosome, the editosome and the spliceosome.
Not to forget a very important feature, RNA groups retain memory of past events via
outliers, that are rejected or even degraded as “non-self”in former interactions but in
more recent events and depending on the real context of interaction they may be
integrated again into a group. Their survival does not depend on selection of a “fittest
type”but rather on an ongoing process of selection for heterogeneity (Villarreal and
Witzany 2019). As we know from current virology, even highly fragmented parasitic
genetic elements can create new RNA networks that are directly involved in gene
regulation found in organisms in all domains of life. This is not error, but pure
productivity. This is a creative process, not copying previous elements, but generating
genuinely new ones (Witzany 2020b). There is a crucial difference between interpreting
RNA structures as results of error replication events, or as events of creative produc-
tivity. The one designates the mechanistic paradigm of the 20th century –the other, a
paradigm that integrates more recent empirical knowledge on the capabilities of
viruses, their relatives, and subviral RNA networks, therefore representing an increase
in explanatory power than the previous one.
This Is Not an Error: Eukaryotes, Eukaryotic Nucleus, Placenta
and Memory Proteins
What formerly was explained by a series of rare beneficial error replication events that
lead to more complex evolutionary innovations can now be better understood avoiding
this 20th century narrative. Lynn Margulis demonstrated convincingly that an evolu-
tionary key event –the emergence of eukaryotic cells –was not the result of chance
mutations of prokaryotic cells, but the merging of former free living prokaryotes into a
social group that could be genetically conserved and heritable (Witzany 2006b). Also
the evolution of the leading proponent of this process, the eukaryotic nucleus must
seemingly have descended from a large double-stranded DNA virus which was able to
build membrane structures and coordinate genetic integration of the various participants
of the eukaryotic cell (Takemura 2020). Also the placenta organ of mammals is not the
result of a series of mutation processes, but dates back to a massive persistent viral
infection of egg laying mammals, as it transferred retroviral syncytin genes that could
protect the foreign embryo from the immune system of the mother by forming a certain
layer of fused cells (trophectoderm) until the immune system of the growing embryo is
strong enough to protect itself (Villarreal 2016). Also, the synaptic arc protein, which is
a crucial player in storing neuronal based memory, stems from persistent retroviral
infection (Pastuzyn et al. 2018). These few examples show that genetic novelty that
leads to evolutionary innovation is not the result of error replication events but of
creative productivity outlined by an abundance of RNA networks transferred by genetic
parasites via persistent infections into host organisms.
Noble’s review uncovers weakness of the scientific concept of the “new synthesis”that
represents the mainstream narrative in the 20th century to explain evolutionary pro-
cesses. This review could be usefully extended to integrate some crucial features of
RNA networks and viruses. Viruses and their defective parts play essential roles in
genetic content composition, and arrangements that help organisms rearrange genetic
content for adaptational purposes in a non-mechanistic way, such as in immune systems
or in the evolution of new organs, e.g., the placenta. Because nearly all the remnants of
former infectious genetic parasites share a repeating nucleotide syntax, in contrast to the
protein- coding non-repeating nucleotide syntax, we now know that, in most cases, they
remain as non- coding RNAs playing essential roles in gene regulation in all organisms
of all domains of life.
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