NATURAL GENETIC ENGINEERING AND NATURAL GENOME EDITING

Cell-Cell Channels, Viruses, and Evolution

Via Infection, Parasitism, and Symbiosis toward
Higher Levels of Biological Complexity
František Baluška
University of Bonn, Bonn, Germany

Between prokaryotic cells and eukaryotic cells there is dramatic difference in complex-
ity which represents a problem for the current version of the cell theory, as well as for
the current version of evolution theory. In the past few decades, the serial endosymbi-
otic theory of Lynn Margulis has been confirmed. This results in a radical departure
from our understanding of living systems: the eukaryotic cell represents de facto “cells-
within-cell.” Higher order “cells-within-cell” situations are obvious at the eukaryotic
cell level in the form of secondary and tertiary endosymbiosis, or in the male and fe-
male gametophytes of higher plants. The next challenge of the current version of the
cell theory is represented by the fact that the multicellular fungi and plants are, in fact,
supracellular assemblies as their cells are not physically separated from each other.
Moreover, there are also examples of alliances and mergings between multicellular
organisms. Infection, especially the viral one, but also bacterial and fungal infections,
followed by symbiosis, is proposed to act as the major force that drives the biological
evolution toward higher complexity.

Key words: cell theory; cell-cell channels; complexity; energides; evolution; infection;
invasion; symbiosis; viruses

Motto: Life is inherently infective and invasive.
Problems with the Current Version
of the Cell Theory and Evolution
Toward Higher Levels of Biological
Complexity
The current version of the cell theory faces
several problems.1–4 First of all, eukaryotic
cells often fuse together partially, via cell-
cell channels allowing transcellular transport
of even such large organelles as mitochon-
dria or nuclei. Moreover, developing cells also
fuse completely forming multinuclear coeno-
cytes. Alternatively, mitotic cell divisions are
sometimes not followed by cytokinesis, result-
ing in syncytia. In fact, this feature is typ-
ical for coenocytic algae, plants, and fungi
Address for correspondence: František Baluška, University of Bonn,
IZMB, Kirschallee 1, 53115 Bonn, Germany. baluska@uni-bonn.de
Natural Genetic Engineering and Natural Genome Editing: Ann. N.Y. Acad. Sci. 1178: 106–119 (2009).
doi: 10.1111/j.1749-6632.2009.04995.x  c 2009 New York Academy of Sciences.
which are, in strict sense, not multicellular
but rather supracellular organisms.1–5 All these
phenomena make the classical cell theory un-
tenable and call for some subcellular unit of
eukaryotic cells that would represent the eu-
karyotic superkingdom. Our previous papers1–5
expanded Daniel Mazia’s cells body6 and
Julius Sachs’s energide7 concepts. Our adap-
tation of these forgotten ideas includes nucleus,
perinuclear microtubule-associated centers,
microtubules, endoplasmic reticulum, and as-
sociated endomembrane systems including or-
ganelles.1,2,5,8–11 As all these organelles are un-
der the control of the cell bodies–energides
(nucleus and microtubules), it is not surpris-
ing that these subcellular units of eukaryotic
life effectively control eukaryotic architecture.
Perinuclear microtubules are inherently dy-
namic showing exploratory dynamic instabil-
ities,12,13 allowing cell bodies–energides to be-
have as integrated structural units able to sense
and explore intracellular space and to mount

106
Baluška: Evolution Toward Higher Levels of Biological Complexity
adaptive responses to exo- and endogenous
cues using molecular motors that control motil-
ities and positions of endomembranes and or-
ganelles.1,2,8–11 The actin cytoskeleton is pri-
marily associated with the plasma membrane
and the cell periphery complex.1,2,10 Never-
theless, the cell body–energide also gained
control about this second major part of the
eukaryotic cytoskeleton via nucleo-cytoplasmic
shuttling of G-actin, crucial actin-binding pro-
teins, and nuclear myosins.14–17
Endosymbiotic origin of eukaryotic cell or-
ganelles is fully accepted now. It is strange that
this radical change of our understanding of eu-
karyotic cell evolution was accomplished rather
quietly, within the last three to four decades.
All this started with Lynn Margulis who revi-
talized the almost forgotten ideas of Constantin
Mereshkovsky18–20 in the sixties and seventies
of the last century.21,22 At that time, despite
several evidences compiled by Lynn Margulis,
there was almost no intellectual support for this
rather controversial view of evolution.23 How-
ever, technological advances allowing sequenc-
ing of rRNA genes in plastids and mitochon-
dria confirmed the bacterial ancestry of these
organelles.24 This means that the eukaryotic
cell is, in fact, a multicellular assembly having
“cells within a cell.” Surprisingly in this respect,
Lynn Margulis is almost forgotten in the con-
temporary symbiotic literature. For example,
the recent issue of the Nature Reviews of Microbio-
logy (Volume 6, Number 10) fully devoted to
symbiosis and its impacts on biology, including
four “full review articles,” one “analysis arti-
cle,” and one “perspective essay” failed to refer
to Lynn Margulis even once from over 550 ref-
erences cited in these articles altogether.
Endosymbiotic Origin of Eukaryotic
Organelles: Eukaryotic Cells as
“Multicellular Organisms”
Eukaryotic cells are a large consortia of for-
merly indepedent cells that partially or fully lost
their identities. Even eukaryotic cells can be in-
107
ternalized by other eukaryotic cells and then
transformed into endosymbiotic organelles by
their dramatic evolutionary reduction.2,25 Im-
portantly, DNA is effectively transported into
the host nucleus whereas the guest nucleus pro-
gressively loses DNA molecules.26–30 Both mi-
tochondria and plastids are well characterized
in this respect.26 This intracellular gene trans-
fer obscures eukaryotic trees based on DNA
sequences,28–30 similarly as it is the case with
the horizontal gene transfer between differ-
ent organisms.30–32 Generally, intracellular par-
asites and endosymbionts accomplish reduc-
tive evolution, which is associated with loss
of DNA. There is at least one example when
all DNA molecules were lost during evolution.
In the case of mitosomes, all DNA was lost,
but these minute organelles still maintain their
double-membranes,32–35 and mitosomes were
demasked as highly reduced mitochondria.33,34
Thus, peroxisomes might be the next potential
candidate for endosymbiotic organelles36,37 de-
spite lacking a genome. In principle, other or-
ganelles and vesicular compartments, includ-
ing endoplasmic reticulum, Golgi Apparatus,
diverse endosomes, and even vesicles, might
represent strongly reduced vestiges of previ-
ously freely living organisms. The reductive
evolution—if taken a sufficiently long time—
might completely obliterate all previous “or-
ganismal” features of these highly reduced en-
dosymbionts. Of course, all this will remain on a
speculative level for some time. Nevertheless, it
is quite obvious that certain trends repeat them-
selves in biological evolution again and again.
Symbiosis, which is repeatedly accomplished
at all levels of biological complexity, is a very
convincing example of this non-Darwinian, but
rather Margulisian evolution.4
Convincing examples of this “endosymbiotic
drive” are secondary and tertiary endosymbi-
otic events when complete eukaryotic cells, to-
gether with their plastids, are internalized.38–40
Although secondary symbiosis is mostly asso-
ciated with plastid-containing cells, resulting
in four membranes enclosing primary plastids,
there are also examples for nonplastid cells.41
108
There are even examples of tertiary endosym-
biosis, which can be identified by the number
of parallel membranes as these are more resis-
tant to obliteration during reductive evolution
typical for endosymbionts.
Relatively recent endosymbiosis events42
suggest that differences between endosym-
bionts and eukaryotic orgenelles gets slowly
blurred.43,44 Moreover, animals can develop ef-
fective symbiotic relationships with photosyn-
thetic endosymbionts.45–47 So there is no fun-
damental difference between plants and ani-
mals in this respect. This very strong evolution-
ary drive for endosymbiosis gives us a unique
opportunity to study evolution in its actual
process.
These days, there are serious problems with
corals, which lose their symbiotic organelles
due to increased temperatures and acidifying
of oceans.48–50 Without their symbionts, corals
deteriorate rapidly. This suggest that endosym-
biosis provides the host cells and organisms with
adaptive advantage, making it a real evolution-
ary force. Another example, which we discuss in
more detail below, where organismal merging
provides adaptive advantages, are well-studied
endosymbioses of plant root cells with mycor-
rhiza fungi and Rhizobia bacteria.51,52
Obviously, symbioses are widespread, abun-
dant, and evolutionarily persistent.53 Despite
the fact that symbiosis was already known in
Charles Darwin’s time,54,55 this phenomenon
was not considered to be relevant for evolution
at that time. One weakness of Darwin’s prin-
ciples of evolution is that these are not strong
in explaining evolution toward the higher com-
plexity.4,56,57 Obviously, both partial or com-
plete fusion of cells, as well as merging of di-
verse organisms, are rather regular processes
which increase the biological complexity rather
radically. With respect of very long evolution-
ary periods necessary for other innovations, en-
dosymbiosis mediated an increase of biologi-
cal complexity and was accomplished rather
quickly.
“Cells-in-cell” assemblies are common in the
sexual reproduction of plants as both female
Annals of the New York Academy of Sciences
and male germ units are represented by several
cells localized within one cell.58–60 Interestingly
in this respect, the “cell-in-cell” phenomenon is
also a characteristic feature for spore formation
in bacteria and fungi.61,62 A very conspicuous
example in this respect is provided by spores
of mycorrhiza fungi when one spore (cell) con-
tains several hundreds of genetically different
nuclei.52,63 Moreover, syncytia are typical for
plant endosperms nourishing plant embryos64
and early embryos of some animals.65 “Cells-
in-cell” situations are characteristic also for ani-
mals and humans.66 Moreover, very prominent
examples of animal-human syncytia are mus-
cles and placenta, as discussed below. At least
for placenta, the viral input is quite obvious and
accepted.67
Intracellular Synapses of
Eukaryotic Cells: Via Synaptic
Integration Toward
Individualization at Higher Levels
of Cellular Complexity
How can the multiorganismal consortium,
such as a eukaryotic cell, achieve its own iden-
tity? One possibility would be that, in anal-
ogy to the cell-cell communication of multicel-
lular organisms across transcellular synapses,
when immuno- and neurosynapses are
responsible for the self, intracellular “cells” of
eukaryotic cells would assemble and maintain
intracellular synapses. In accordance with this
synaptic perspective, eukaryotic cells are char-
acterized with numerous appositions of two
membranes such as nuclear, mitochondrial,
plastid envelopes, or Golgi Apparatus, and en-
doplasmic reticulum membranes.
Two closely apposed membranes commu-
nicating extensively are typical for phago-
cytosis in eukaryotic cells. Recently, this
phenomenon fostered the introduction of
phagocytic synapse69,70 as another new mem-
ber of the synaptic family. Cell-cell adhe-
sion and signalling domains between host
and pathogen cells, so-called phagocytic
Baluška: Evolution Toward Higher Levels of Biological Complexity
synapse,70,71 serve as communication devices
for phagocytosis. Signalling across the phago-
cytic synapse is complex69–71 and resembles sig-
nalling across the immunological synapse.
The phagocytic synapse concept is useful for
plant cells too. Bacteria of genus Rhizobia en-
ter plant roots of genus Fabaceae via a fungal-
like infection thread, which is a transcellular
tube generated via inverted tip growth induced
by bacteria enclosed via plant plasma mem-
brane and cell wall.72 Bacteria are enclosed
by a fluidized cell wall72 and internalized into
root-derived nodule cells in the form of sym-
biosomes enclosed by a synaptic double mem-
brane.73 A much more dramatic example of the
endosymbiotic synapse in plants68 is the mem-
brane interface between host root cells and
mycorrhiza fungal hyphae.51 In this case, large
areas of the plant–fungal synaptic double mem-
branes extend throughout the root inner cor-
tex, resembling tip growing infection threads
of Rhizobia.68 Interestingly in this respect, there
are similar signalling aspects, using the same
signalling molecules, in the bacteria–plant and
fungal–plant symbiotic interactions.51,52,74 Re-
cently we proposed68 that in order to build a
composite plant/fungal cell,51,74,75 the partners
need to reach compatibility via balanced synap-
tic68 communication of both partners, similarly
as it was in the case described above of en-
dosymbiotic algae.
Besides organellar synapses, one could en-
vision interorganellar synapses when the outer
membranes of organelles often show temporary
contacts with other organelles forming inter-
organellar synapses. These temporary synapses
resemble immunological synapses in many as-
pects.68 In plant cells, there are close con-
nections between the plasma membrane (PM)
and the cortical endoplasmic reticulum (ER)
in plants.76 Such ER-PM junctions are inher-
ent also for excitable animal cells.77–80 Junc-
tiophilins were discovered as a novel family
of junctional membrane proteins which keep
closely apposed membranes of this synaptic
ER-PM complex together.80 Importantly, these
proteins contain the MORN-motif repeat too
109
and have essential roles for the excitability of
synaptic activities of neurons.79–81
Moreover, there are intimate contacts
between endoplasmic reticulum and other
organelles, such as mitochondria,82 peroxi-
somes,83 and lipid bodies.84 But other or-
ganelles are also known to enter into similar
synaptic interactions (for review see Ref. 85). A
recent study revealed interorganellar synapses
composed of the outer plastid membrane—
a plasma membrane interaction domain me-
diated by G-protein GPA localized to the
plasma membrane and THYLAKOID FOR-
MATION1 protein localized to the outer mem-
brane of plastids.86 Another striking example
of the plastid-plasma membrane intracellular
synapse is the eyespot apparatus of green al-
gae in which, beside the plasma membrane
and two plastid envelope membranes, the thy-
lakoid membranes are also closely apposed (see
Fig. 1B in Ref. 87). Proteomic analysis of the
eyespot apparatus of Chlamydomonas reinhardtii
revealed, besides several signalling molecules
such as protein kinases, phosphatases, calcium-
binding proteins, photoreceptors, also a synap-
tic MORN-motif repeat protein and adhesion
protein containing fascilin I domains.87 In-
terestingly, excitation of this eyespot synapse
induces rapid electrical responses leading to
changes in flagellar beating and phototaxis.88
Intracellular synapses give strong support for
the “conscious cell” concept proposed by Lynn
Margulis.89 This concept provides an expla-
nation for the complex behavior of eukaryotic
cells in the face of a huge amount of infor-
mation that they continuously monitor, receive,
store, and process for making adaptive decisions
about their further states and activities.89,90 For
instance, amoeba Physarum behaves as a smart
organism capable of solving complex geomet-
rical puzzles, showing signs of memory, antici-
pation, learning, as well as several other aspects
of cognitive and intelligent behavior.91–96 The
proposed algorithm behind this intelligent be-
havior of Physarum turned out to be simple and
powerful.97 Moreover, integrative information
processing, memory storage, and computation
110
occurs at subcellular levels of neurons, whereas
the single neuron represents the elementary
unit for computation in the human brain.98
Similarly, as in unicellular protists,88 there
are also intraneuronal action potentials linking
the synapse with the energide.99 Intracellular
synapses are likely to increase the computa-
tional capabilities of the eukaryotic cell.100 One
can consider the synaptic membranes for smart
scaffolds, which keep signalling complexes in
optimal topological distances from each other
in order to optimize information perception,
processing, and storing. This feature is critical
for computational and information-processing
properties of synapses existing within any multi-
cellular organism as well as within all eukaryotic
cells. Intracellular synapses increase informa-
tion processing and computational properties
of more complex cells which should have pro-
found consequences for the cell theory and cel-
lular evolution.
Cellular Fusion: Developmental and
Evolutionary Implications
Cells of multicellular organisms often accom-
plish partial or complete fusions. As discussed
above, almost all cells of higher plants are inter-
connected via plant-specific cell-cell channels
known as plasmodesmata. Similarly, multicel-
lular fungi are also supracellular and recently
animal-specific cell-cell channels, so-called tun-
neling nanotubules, have been discovered in
cell cultures.101–103 Although it is still not cer-
tain if these tunneling nanotubules are relevant
for animal organisms, one cannot rule out that
such cell-cell channels are also interconnect-
ing animal and human cells within intact tis-
sues. In addition, there are several common
features between syncytial tissues of animals,
such as muscles, and supracellular plants, in-
cluding diffuse microtubule organizing centers
(MTOCs) as well as mobile trans-Golgi net-
works (TGNs).3,4
What is the evolutionary origin of cell-cell
channels? Clues are provided both by plants
Annals of the New York Academy of Sciences
and animals in which viral infections not only
manipulate existing cell-cell channels but also
can induce de novo formation of new cell-cell
channels (see below). Even bacteriophages need
to make a channel across bacterial cell walls
and membranes in order to deliver its ge-
netic material into a bacterial host cell. Both
in prokaryotic and eukaryotic cells, infection
and sexual repreduction are based on cell-cell
channels, and on partial or complete cell-cell
fusions, in order to allow exchange of DNA
molecules. Could it be that the sexual repro-
duction is heritage of ancient infections or
invasion events? Massive incorporation of in-
vasive viral DNA into genomes, when for ex-
ample up to 40% of the current mammalian
genome is represented by repetitive endoge-
nous retroviruses sequences,104 strongly sug-
gests that these viral parasites shape the evo-
lution of genomes.104,105 Interestingly, these
viral-derived sequences gained structural (epi-
genetic) control over spatial arrangement and
expression of the genome,105 indicating a sur-
prising conclusion that viruses (parasite) gained
control over the genome (host) during genomic
evolution.
Virus-Induced Cell-Cell Synapses
and Cell-Cell Channels
In order to accomplish effective colonization
of large multicellular organisms, viruses induce
the formation of specialized cell-cell adhesion
domains, known as synapses, to spread from
cell-to-cell. Similarly, viruses manipulate ani-
mal cells to induce cell-cell channels for their
own sake—to get access to as many cells as pos-
sible.106–108 Is it possible that cell-cell channels
and cell-cell fusions in plants and animals are
of ancient viral-induced origin? At least for the
placenta, the viral origin is obvious.67
If viral infections result in more effective
cell-cell communication, then one could spec-
ulate that repetitive viral infections contributed
to the better coordination of individual cells
of multicellular organisms. This speculative
Baluška: Evolution Toward Higher Levels of Biological Complexity
scenario gets support from recent advances in
our understanding of how viruses spread from
cell-to-cell. They induce viral synapses, special-
ized cell-cell domains which are effective in al-
lowing cell-cell spread of viruses.109–112 Sim-
ilarly, as in plant cells, these viruses induce
cell-cell channels to achieve free passage from
cell-to-cell.106 Interestingly in this respect, plant
viruses, such as the Rice Dwarf Virus, are able
to generate actin-based filopodia-like protru-
sions which grow into adjacent cells, not just
in plants but also in animal/insect vector tis-
sues.113,114 Besides endosomes,103 endosymbi-
otic mitochondria can also use these cell-cell
channels for their transcellular spread.115 It is
obvious that we still do not understand the true
complexity and integrated supracellular nature
of multicellular organisms.
Virus-Induced Membrane and
Organelle Manipulations
Viruses manipulate membranes of eukary-
otic cells at the plasma membrane as well as
at all membraneous organelles.116 It can be
proposed that not only the nucleus117–121 but
almost all eukaryotic features of membrane
events including endocytosis, vesicle formation
at diverse intracellular compartments and or-
ganelles, as well as exocytosis might be consid-
ered for vestiges of ancient virus-induced ma-
nipulations of eukaryotic membranes.116,122–126
Virus-induced manipulations of cells and
their membranes have impacts on evolution.
Viral infections are causing problems at the
organismal level, when infected organisms are
forced to fight back and often use the viral-
induced structures and processes for their ad-
vantage and benefit. Besides endocytosis, exo-
cytosis, vesicle trafficking, cell-cell fusions, and
many other processes emerge to have origins in
ancient viral infections. For example, in order to
allow entry into cells, diverse endocytosis path-
ways are manipulated.126 For efficient intra-
cellular replication, viruses manipulate intra-
cellular membranes.115,122,124,125 Viruses also
111
induce partial or complete cell-cell fusions and
this may result in important novelties, such as
the supracellular nature of plants or the above
mentioned placenta of animals.67
Organismal Merging: The Next
Source of Evolutionary Complexity
Lichens represent one of the best exam-
ples of two multicellular organisms, fungi
and algae, merging together to form a
fully integrated mycobiont-photobiont organ-
ism.55,127–129 Lichens have unique survival and
tolerance properties, which one would not ex-
pect knowing both partners separately. This
unrivaled ability to survive the harshest envi-
ronmental condition,130,131 when lichens are
able to survive even outer space conditions132
might be relevant during the first waves of land
colonization by multicellular organisms. In the
future, if our civilization decides to spread life
outside of the Earth, lichens will be the prime
candidate. Interestingly in this respect, about
one fifth of all known fungal species are derived
from lichen symbiotic ancestors.133
Although higher plants are generally con-
sidered to represent advanced algae, there are
numerous indications that, during their in-
vasion of land, algea fused completely with
fungi to generate chimeric plants akin recent
lichens,127,128 which allowed successful colo-
nization of land. This breakthrough event pre-
pared suitable conditions for the subsequent
sea-land move for animals. This fungal view
of higher plants134–137 is not popular among
botanists, but there are several features of
higher plants not present in any algae.136 We
can briefly mention invasive pollen tubes and
root hairs of autotrophic plants and invasive
haustoria of heterotrophic parasitic plants, as
well as several fungal-like cells, including inva-
sive laticifers, xylem, and phloem cells. Not only
do pollen tubes grow via fungal-like tip growth
but, in cycads, Pinus, and Ginkgo they are also
branched and absorb, in a parasitic fashion, nu-
trients from host megasporangium. Similarly,
112
as it is the case in lichens, when autotrophic
algal cells/tissues are interspersed between
heterotrophic fungal cells,127,128 also in higher
plants we have green autotrophic cells/tissues
which are enclosed by nongreen heterotrophic
cells/tissues. Even in photosynthetic leaves,
only portions of cells have green photosynthetic
plastids (parenchymatic cells below epidermis)
whereas most other cells are heterotrophic, sim-
ilarly as it is the case with all root cells. Interest-
ingly in this respect, recent mycorrhiza fungi in-
vade only cortical root cells, which corresponds
to those leaf cells active in photosynthesis, but
not epidermis cells and stele cells.74,75,137,138
Higher plants not only have the upper (shoot) –
lower (root) polarity but also the outer (cortex)
– inner (stele) polarity.139 Photosynthetic cells
of higher plants are present only in the cortex
cells of above-ground organs, especially leaves,
which is the smaller part of all plant body cells.
All other plant cells are heterotrophic and seem
to be of fungal origin. This pattern of distribu-
tion of autotrophic and heterotrophic cells of
higher plant organs closely resembles the dis-
tribution pattern of algal and fungal cells in
lichens.127,128
Organismal fusions are relatively well stud-
ied in two rather dramatic examples in plants.
Roots of most plants make consortia with my-
corrhiza fungi which improve plant nutrition
and stress tolerance.51,52,54,75,137,138 This merg-
ing of mycorrhiza fungi and plant roots dates
back to the ancient move of plants from the
sea to land.137,140 More recent merging be-
tween roots and bacteria of the genus Rhizo-
bium is evolutionarily younger and limited to
only a few plants.138 However, both the sig-
nalling molecules and cascades important to
recruit Rhizobium endobacteria are very sim-
ilar to those involved in root establishment—
mycorrhiza symbiosis.52,141 In both cases, it
seems that plant roots and their cells actively
lure both mycorrhiza and bacterial cells into
root apices and their cells.142–144 These in-
terorganismal symbiotic “cells-in-cell” as well
as “multicellular organisms within multicellular
organisms” phenomena are obviously impor-
Annals of the New York Academy of Sciences
tant for higher plants. Higher plants emerge as
a fully integrated lichen-like fungus – algae al-
liance which allowed land colonization.134–137
If such a scenario is confirmed in the future,
then plants would represent the most recent full
merging between two multicellular organisms.
Fungi are extremely invasive and plague al-
most all multicellular organisms. Recently, mi-
crosporidia, which are obligate intracellular
parasites of animal and human cells and have
accomplished dramatic reductive evolution,145
have been demasked to represent highly re-
duced fungi related to zygomycetes.145–147 In
this invasive feature, fungi closely resemble
viruses and bacteria, which are also highly
infectious agents. As mentioned above, some
plant cells, and even whole (parasitic) plants,
are very relevant with respect to plant-fungi
similarities. In addition, pollen tubes, as well as
infectious threads assembled by plant cells to
bring into roots symbiotic bacteria, as well as
haustoria of parasitic plants, all are performing
invasive growth. What is clearly emerging from
all of the above studies is that infection is an in-
herent property of life which shapes and drives
evolution toward higher complexity.
“No Infection – No Evolution”:
“Principle of Cruelty” Drives
Evolution Toward Higher
Complexity via “Principle of Love”
Gejza Vámoš proposed that viral and bacte-
rial infections represent the “principle of cru-
elty” and that this negative principle induces
the positive principle—“principle of love.” 148
Vámoš was not discussing evolution of eukary-
otic cells, and he was also not aware of the
endosymbiotic origins of eukaryotic organelles.
But if added to the classical Darwinian prin-
ciples of evolution, his two simple but power-
ful principles allow understanding of the cel-
lular evolution toward increased complexity.
Repeated infection – symbiosis cycles are eas-
ily explainable by interactions between the
“principle of cruelty” (infection, predation) and
Baluška: Evolution Toward Higher Levels of Biological Complexity
the “principle of love” (symbiosis, coopera-
tion). Repetitive cycles of these two simple, but
powerful, principles allow us to understand,
and even to predict, evolution not only to-
ward multicellularity but also toward higher
order mergings between multicellular organ-
isms. For example, consider fungi and algae in
lichens,127,128 or mycorrhiza fungi and plant
roots.51,52,75,138,149,150 In addition, these two
principles seem to have general validity for so-
ciology, including very complex human affairs,
such as family ties, wars, states, and civiliza-
tions; and potentially even for general physics
and chemistry. Indeed, dynamic interactions
and repeated cycles of these principles might
tell us more on the emergence of life from the
anorganic systems and its subsequent spread
into adjacent possible.56,57 Life is inherently in-
fective and invasive.
The recent dicovery of horizontal gene trans-
fer of algal nuclear genes to animal host cells
in the photosynthetic sea slug Elysia chlorot-
ica is a very nice example that endosymbio-
sis generates “green animals.”27 This process
implicates, as predicted by Lynn Margulis,151
the production of new lineages and speciation
via endosymbiotic acquisition of genes, whole
genomes, and metabolic novelties. These au-
thors,27 in contrast to many others, paid the
tribute to Lynn Margulis and her evolutionary
ideas on evolution.21,22,151
Conclusions
Our understanding of biological evolution,
if based solely on the Darwinian principles, is
weak in explaining why it should proceed to-
ward higher biological complexity.4,56,57 When
viruses and bacteria were in ancient times, and
still are, so well adapted to the environment
present on the Earth; why should higher or-
der complexity biosystems emerge and further
increase their biological complexity? In fact,
despite their very long evolutionary history,
viruses and bacteria currently belong to the
most abundant organisms on this planet.152–155
113
If the classical principles of Charles Dar-
win are combined with the dynamic interac-
tions of two simple principles, as envisioned by
Gejza Vámoš in his PhD study,148 the “prin-
ciple of cruelty” and the “principle of love,”
provide proper answers. Under the pressure
of biological infections (“principle of cruelty”),
all living systems, even if well-adapted to their
physico-chemical environment, are pushed to-
ward higher spheres of the biological complex-
ity via cooperation, aggregation, and merging
(“principle of love”) responses of infected bi-
ological units. It can be proposed that it is
the inherent invasive property of living systems
that causes their strong drive to invade new
niches and to further expand their newly “con-
quered” space to the nearest possible.56,57 This
“nearest possible” also includes intraorganis-
mal niches, such as the cytoplasmic space of
contemporary eukaryotic cells or tissues/cells
of multicellular organisms. This breaks the
previous organismal boundaries leading to
complex consortia-like assemblies consisting of
“cells within cells”1,2,4,5,21,22 and to “multi-
cellular organisms within multicellular organ-
isms.”51,52,75,138,149,150 Under continuing viral,
bacterial, and fungal infection attacks, these
then further increase their complexities until
they eventually achieve the breakthrough of the
next evolutionary boundary of biological com-
plexity. Higher plants emerge to represent a
unique example of the full merging of two pre-
viously separate multicellular organisms.134–137
Lichens are dual organisms55,127,128 and the
same is true for mycorrhiza fungi and plant root
assemblies.51,52,75,138 Importantly, multicellu-
larity was “invented” several times,156,157 and
multicellular organisms are integrated into the
self-based individual via transcellular synapses.
Neuronal and immune synapses, via continu-
ous transcellular communication, generate the
self, which represents a fully integrated individ-
ual at a higher level of biological complexity.
For example, we as humans feel as though we
are individuals, despite the fact that our bodies
include a myriad of bacterial and viral organ-
isms, as well as protozoa.158–161 Contribution
114
of viral infections to “invention” of synapses
is very plausible. Moreover, repetitive cycles of
duplication – aggregation/merging, which are
followed by the subsequent individuation via
so-called Beklemishev’s cycles,156,162,163 are
driving the increase in biological complexity
during metazoan evolution too. All this is an
expression of the simple but powerfull princi-
ples that drive merging-individualization cycles
at the gene, chromosome, genome, and cellu-
lar levels; the Vámoš principles of “cruelty and
love.”
Acknowledgments
The author is thankful to Viktor Demko for
introducing him to the work and ideas of Gejza
Vámoš, and to Ladislav Kovač for inspiring
him to apply the principles of Gejza Vámoš
for an explanation of evolution toward higher
biological complexity.
Conflicts of Interest
The author declares no conflicts of interest.
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