Multicellular organisms have never evolved alone. Coevolution has been accomplished by means of horizontal information transition. A wide row of hierarchized interspecies interactions simultaneously transmitting biological information had evolved in the past. In the present review, we summarize the current hypothesis about possible horizontal exchange of biological information and genesis of adaptive immune system

1. Article Citation:
Petr Šíma and Vaclav Vetvicka.
Horizontal exchange of biological information and genesis of adaptive immune system
Journal of Research in Biology (2015) 5(1): 1619-1626
JournalofResearchinBiology
Horizontal exchange of biological information and genesis
of adaptive immune system
Keywords:
Evolution, Genes, Bacteria, Vertebrates
ABSTRACT:
Multicellular organisms have never evolved alone. Coevolution has been
accomplished by means of horizontal information transition. A wide row of
hierarchized interspecies interactions simultaneously transmitting biological
information had evolved in the past. In the present review, we summarize the current
hypothesis about possible horizontal exchange of biological information and genesis
of adaptive immune system.
001-004 | JRB | 2015 | Vol 5 | No 1
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www.jresearchbiology.com
Journal of Research in Biology
An International
Scientific Research Journal
Authors:
Petr Šíma1
and Vaclav
Vetvicka2
Institution:
1.University of Louisville,
Department of Pathology,
Louisville, KY 40202, USA
2.Department of
Immunology and
Gnotobiology,
Institute of Microbiology,
Czech Academy of Sciences,
Vídeňská 1083, 142 20
Prague 4, The Czech
Republic
Corresponding author:
Vaclav Vetvicka
Web Address:
http://jresearchbiology.com/
documents/RA0481.pdf
Dates:
Received: 16 Sep 2014 Accepted: 19 Dec 2014 Published: 29 Jan 2015
Journal of Research in Biology
An International Scientific Research Journal
REVIEW
ISSN No: Print: 2231 –6280; Online: 2231- 6299

2. Horizontal exchange of biological information has a
substantial role in evolution
The first experimental evidence of the ability of
microorganisms to incorporate the foreign genetic
material into their genomes was referred in 1944 (Avery
et al., 1944). However, the idea of symbiosis of two or
more unrelated organisms, even pro- and eukaryotic, and
consequent exchange of their genetic material through
horizontal pathway, is much older. In 1867, Schwendener
was the first to consider the role of intrinsic coexistence of
two unrelated organisms in evolution. In 1879, De Bary
introduced the concept of symbiosis, which was further
completed by Merezhkowsky into the Theory of
symbiogenesis in 1920. Then, since the end of the 20th
century, owing to the comparative work of Margulis
(1993), it has been clear that the genes of mitochondria,
chloroplasts, and other organelles could be found
incorporated in the genome within the nucleus of their
eukaryotic cells.
Multicellular organisms have never evolved
alone, as evolution does not know a splendid isolation
from other living beings. Not evolution, but coevolution
formatted all organisms since the dawn of life.
Coevolution has been accomplished by means of
horizontal information transition. Acquisition of
horizontally transmitted genes explains the comments
written as early as 1970 (Anderson, 1970). This could be
the answer to Syvanen´s query “Why is molecular biology
so unified?” (Syvanen, 1994).
Defense of self vs. biological information exchange
The evolution of living organisms was
principally the hierarchized mutual coevolution of units,
thermodynamically open systems (Bertalanffy, 1950), so
called the CITROENS (Complex Information
Transforming, Reproducing Objects that Evolved by
Natural Selection), cooperating or competing with each
other for space, nutrition, and survival (Orgel, 1973).
Their life and adaptive radiation were constricted by the
horizontal exchange of biological information, and
simultaneously, by the defense of their internal integrity.
Pathways of biological information exchange
A wide row of hierarchized interspecies
interactions simultaneously transmitting biological
information had evolved in the past, which by means of
various molecules as information vectors and molecular
mechanisms in the role of receivers allowed
communication among non-related micro- and
macroorganisms (Table 1).
Šíma and Vetvicka, 2015
1620 Journal of Research in Biology (2015) 5(1): 1619-1626
*) relations without definition of differences between parasitism and profit
Interrelationship Mutual attitudes Vectors
Neutralism without mutual influence none
Protocooperation relatively free, independent recipro-
cal profit
Attractants, allomones, kairomones, sinomones
Mutualism fully dependent reciprocal profit Attractants, allomones, kairomones, sinomones
Commensalism relatively free profit for only one Attractants, pheromones, kairomones
Amensalism
Antibiosis
Allelopathy
negative influence annihilation of an
organism defense to competition
Inhibitors, antibiotics, deterrents, phytoncides, repellents
toxins
Competition mutual negative influence Inhibitors, antibiotics, deterrents, phytoncides, repellents
toxins
Parasitism attack toward an organism,
pathogenesis, gradual virulence
Inhibitors, antibiotics, deterrents, phytoncides, repellents
Toxins, pathogenicity islands
Table 1. Interspecific relations and interactions among organisms (The symbiosis sensu De Bary (1869))*

3. At least two pathways of biological information
transfer could be regarded as fundamental: 1) the
indirect pathway represents a number of factors and
signal molecules of various chemical compositions,
which are released into the environment (Table 1 and 2)
the direct instructive pathway of biological information
transfer is represented by gene transmission, which is
mediated by an amalgamation of entire genomes of two
or more organisms, insertion of smaller genome regions
like single genes, and parts of genes (nucleotides). In this
case, the vectors represent mobile elements such as
viruses (bacteriophages), conjugative plasmids, free
nucleic acids (insertion elements, gene cassettes),
transposons, genomic islands, and possibly even prions
(Lee, 1996; Hacker and Carniel, 2001; Schmidt and
Hensel, 2004; Prusiner, 1994; Silvestri and Baldassarre,
2000).
Genomes are not protected by an immune system
It is not easy for a microbe, virus, or multicellular
parasite to enter into the internal milieu of a multicellular
eukaryotic organism. The mucus and cell membranes of
the external and internal epithelia are effective barriers
against the foreign invaders. In cases where these borders
have been damaged, or invading parasites developed
mechanisms to penetrate, a machinery of defense is
prepared to their neutralization and annihilation.
Immunocompetent cells producing a row of defense
molecules, including antibodies from immunoglobulin
superfamily, destroy the entire alien from outside.
Generally, there are three groups of enteric
bacterial pathogens categorized on the basis of the
mechanisms by which they cause disease. The bacteria of
the first group, exemplified by Vibrio cholerae and
Escherichia coli, could be characterized by mucosal
adherence and production of enterotoxins, which cause
diarrhea (Levine et al., 1983).
The bacteria of the second group (such as
Shigella) penetrate and proliferate within the intestinal
epithelia, which causes cell death. In some instances, they
discharge enterotoxins increasing lesions (Butzler and
Skirrow 1979; Levine et al., 1983).
Salmonella and Yersinia represent the third
group. These bacteria are able to translocate into intestinal
mucosa, and proliferate in the lamina propria and
mesenteric lymph nodes. Translocation of these bacteria,
particularly S. typhi and S. paratyphi A and B could be
followed by systemic bacteremia (Levine et al., 1983;
Beltran et al., 1988).
From the point of evolutionary view, when these
(and other) bacterial species capable of intracellular life
overcome the host immunity, they could represent
potential vectors or direct donors of genes like
Pathogenicity Islands (PAI), the groups of virulence genes
on bacterial chromosome that could transfer new
biological information into the eukaryotic genome. The
PAI, the term introduced in 1990 by Hacker, may
represent mobile distinct molecular elements that take
advantage of phage integration mechanisms. A question
remains - represent bacteria like Salmonella, Francisella,
and similar intracellular microbes bearing PAI or other
mobile elements, the contemporary evolutionary vectors
of new biological information? Could the infections
caused by these microorganisms in the instance that the
victims survive have evolutionary consequences?
Advent of jaw vertebrates
“One of the great events of revolutions in the
history of vertebrates was the appearance of jaws. The
importance of this evolutionary development can be
hardly overestimated, for it opened new lines of
adaptation and new possibilities for evolutionary
advancement to the vertebrates that expanded
immeasurably the potentialities of these animals. The
appearance of the jaws in vertebrates was brought about
by a transformation of anatomical elements that originally
had performed a function quite different from the function
of food gathering” (Colbert, 1980).
Similarly, the same evolutionary importance
could be attributed to the emergence of the adaptive
Journal of Research in Biology (2015) 5(1): 1619-1626 1621
Šíma and Vetvicka, 2015

4. immune system. System in which not only ancient cells
(like wandering and sessile macrophages), but also the
novelty specific only for deuterostomes, have started new
collaboration and cooperation utilizing and synthesizing
new regulative and defense molecules in newly fabricated
structures, tissues and organs (Table 2).
RAG time and emergence of the adaptive
immune system
Some 500 million years ago, the predecessors of
gnathostomes, the placoderms, emerged in primordial seas
(Flajnik and Masahara, 2010). Possibly in these
forerunners, the genomes of their immunocompetent cells
were waiting for acceptance of new biological information
enabling them by means of highly sophisticated
mechanism of molecular recombination to transform
immunoglobulin superfamily molecules into effective
defense vectors, the T and B receptors, antibodies, MHC,
and other molecules needed for functions of the adaptive
immune system.
Three events influenced the emergence of
adaptive immunity: evolution of gnathostomean basic
body pattern inclusive jaws, differentiation of new
immunocompetent structures inclusive lymphoid tissue
(particularly GALT), and acceptance of mobile
transposons of bacterial origin, the RAGs (Recombination
Activation Genes) allowing V(D)J recombination of
molecules of immunoglobulin superfamily (Sakano et al.,
1979; Agrawal et al., 1998) (Table 3).
Why RAGs transposed just into lymphoid cells?
The capability of translocation of intestinal
bacteria throughout the mucous lining and across
epithelia, and to penetrate into and survive within the
certain developmental stages of ancestral rapidly
renewing cell populations like lymphoid cell lineage,
could represent mechanisms of a new genetic information
transfer in the form of gene cassettes like RAG
transposons (Agrawal et al., 1998;Hiom et al., 1998;
Hansen and McBlane, 2000). On the other hand, the same
is true about the disability of primitive
immunorecognition of their hosts and a slightly effective
immune response to destroy them.
It has been generally accepted that lymphoid
cells in a role of intraepithelial immunocompetent cells in
all walls of the body make up at least a half of all the
lymphocytes the mammalian immune system possesses.
They are loners – slowly wandering free cells among the
epithelial cells. Evolutionary pressures like the threat of
decay of integrity of organisms caused by pathogens or
parasites and to counter the effects of somatic potential
carcinogenic mutations may be sufficient stimuli to
Šíma and Vetvicka, 2015
1622 Journal of Research in Biology (2014) 5(1): 1619-1626
Taxon Cells Organs Molecules
Echinoderms lymphoid-like axial organ Ig
Protochordates lymphoid-like - Ig
Chordates lymphoid-like stolon -
Agnathans lymphoid typhlosole Ig
Gene cassettes incorporation into lymphoid cell lineage
Gnathostomes lymphocytes thymus RAG, TCR, BCR etc.
GALT
bursa Fabricii-like
spleen
lymph nodes
Table 2. Evolutionary consequences of gnathostomean basic body plan. Morphofunctional
prerequisites for adaptive immunity

5. develop rapidly renewing and specialized cell lineage that
could neutralize these threats (Millar and Ratcliffe, 1989).
The first lymphoid-like cell populations endowed
with the primitive T and B diversity were documented in
the axial organ of deuterostomian echinoderms, which is,
moreover, supposed as phylogenetic homolog of the
vertebrate spleen (Leclerc et al., 1993).
Urochordates contain several morphologically
distinct free cell types, but from the point of view of their
morphology and immune functions, the most important
cell type is considered to be the lymphocyte-like cell,
known also by name, the lymphocyte. The biological
characteristics of these cells include the participation in
encapsulation, allograft rejection, cytotoxicity,
proliferative response and immune memory (Sawada et
al., 1993).
In cyclostomes, the lymphohemopoietic cell
aggregations accompanying the veins in the intestine
submucosa are considered as an early form of GALT. In
these animals, which lack true thymus and spleen, these
aggregations form about one-tenth of the gut wall volume
(Grozdinski, 1926, Tanaka et al., 1981). In the larval stage
of the ammocoete, the main lymphohemopoietic organ
most often homologized to vertebrate spleen or bone
marrow is a longitudinal infolding along the anterior
intestine, the typhlosole (Šíma and Slípka, 1995) (Table
2).
In elasmobranches, the first living gnathostomean
vertebrates, the Leydig organ represents the important
lymphomyeloid structure associated to the anterior gut
(Zapata 1981; Zapata and Cooper 1990).
In osteichthyan fish, the presence of gut
lymphoid tissue has been documented, although they do
not possess structures like follicles resembling Peyer´s
patches (Hart et al., 1988).
In amphibians, the first vertebrates, which have
adapted to terrestrial life, the intraepithelial lymphoid
cells within the gut lamina propria and encapsulated
lymphoid structures in the oesophagus have been
described (Ardavin et al., 1982; Wong, 1972).
Intraintestinal epithelium of reptiles contains
numerous intraepithelial lymphoid cells including
plasmacytes. Lymphoid cell aggregates in the gut
submucosa resemble Peyer´s patches precursors in
mammals. Similar accumulations were found on body
locations of avian bursa of Fabricius or mammalian
appendix (Solas and Zapata, 1980, Zapata and Solas,
1979).
Birds possess the well-developed GALT exerting
many similarities to that of mammals: Peyer´s patches
(Basslinger, 1858; Befus et al., 1980), cecal lymphoid
nodules and tonsils (del Cacho et al., 1993; Glick et al.,
1981), and in addition, the cloacal diverticulum
specialized to B cell development and production, the
bursa of Fabricius (Glick, 1978; Jeurissen et al., 1989)
(Table 2).
What happened before the emergence of
gnathostomian vertebrates?
It may be hypothesized with a high probability
that the lymphoid cell lineage of predecessors of
gnathostomes was sufficiently plastic for acceptation of
RAG gene cassettes and for incorporation of them into
suitable loci of chromosomes. According to current
Journal of Research in Biology (2014) 5(1): 1619-1626 1623
Šíma and Vetvicka, 2015
- Unrelated in sequence, tightly linked
- Cleavage pathway similar to steps involved in DNA transposition reactions
- Retroviral type of integration
- DNA breakage and rejoining by means of trans esterification of mobile elements
- RAG and HIV integrases use alcohol instead of water as the nucleophile in the DNA cleavage reaction
Table 3. Characters of Recombination Activation Genes (RAG1 and RAG2) suggesting horizontal transfer

6. knowledge, the sources of RAGs had to be some species
of bacteria that could enter into lymphoid cells, adapt to
intracellular life, and transport a part of their chromosome
into nuclear genome apparatus. These originally infectious
bacteria could be endowed by a low degree of virulence
and might be capable to co-exist within cells for many
millions of years in some form of symbiosis like
protocooperation, mutualism or commensalism (Table 1).
Several questions remain. One focuses on
contemporary intracellular parasites such as Salmonella,
Shigella, Francisella etc., serving as potential vectors of
new biological information. Can they be considered an
evolutionary novelty? Are extant birds and mammals
bearing intracellular parasites in their highly organized
GALT interconnected with gut epithelia the predecessors
of new species endowed with new evolutionary features
like the ancestors of gnathostomes?
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