Adaptive immune system did
not evolve by
mutations and selection
Dr Alfred Schurmann - computer
scientist and mathematician
1. Introduction. It
is uncertain how the adaptive immune system evolved (s. J. Neumann
[NEU]: Immunologie, 2008,Kap. 7.6). At the first sight, it evolved
evolutionary from an ancestor system (as suggested in B. Lewin [LEW]:
Genesis IX, 2008, Sec. 23.20, in J. Klein [KLE]: Der Stammbaum der
Wirbeltiere und der Ursprung des adaptiven Immunsystems (in German),
and in T.A. Brown [BRO]: Genomes3, Garland Science Publishing (2007),
Sec. 18), because: (a)
non-vertebrates have innete (nonadaptive) immune system, (b) some genes
(i.e. mete-programs), e.g. SpRag1L
and SpRag2L, which
occur in sea urchin are homologous to genes (meta-programs), e.g. Rag1/2,
used in adaptive immune system (s. J. Neuman [NEU], Kap. 7.6),
some jawless fishes (lamprey and hagfishes) have cells that resemble
lymphocytes of jawed vertebrates very closely (s. J. Klein [KLE]), but
they are not capable of adaptive immune response, (d) jaw vertebrates
have adaptive immune system. However, if we think over this reasoning,
then we may have serious doubts whether it is correct. Firstly, we have
no evidence that random mutations and selection changed some genes in
non-vertebrates into genes of adaptive immune system. Secondly, such
reasoning does not solve the problem of the origin of adaptive immune
system, because we do not know what properties had this ancestor system
and how it evolved. Also, it is only a belief that an ancestor
transposon (as suggested in B. Lewin [LEW], Sect. 23.10) could
transform genes into genes (meta-programs) for recombination of immune
genes. As J. Neumann [NEU] (Sec. 7.6) pointed out, the question of the
origin of adaptive immune system has not been answered.
Below, I prove that actually, adaptive immunity did not evolve
evolutionary by random mutations and selection. First I characterize
essential properties of adaptive immune system. Then I list the
possible mutations (operations), which may alter an animal system. Then
I show that a finite sequence of random mutation operations cannot
meta-programs (genes) which do not belong to adaptive immune system in
very complex and integrated meta-programs belonging to adaptive
2. Some essential properties of
denotes family of meta-programs (i.e. eukaryote genes) having the
The adaptive immune system contains lymphocyte cells B or T and the major histocompatibility
locus (called MHC locus);
each of these components contain many linked meta-programs belonging to
the family AIP, which produce
many simpler meta-programs of the adaptive immune system. B lymphocytes
have meta-programs (i.e. eukaryote genes) which assemble simpler
meta-programs (genes) from DNA segments (which are genes) and these
produce immunoglobuline (in short Ig)
proteins, called antibodies, specific for a foreign molecule (which are
associated with antigens); Ig
proteins are operations which recognize these antigens and help to
remove or kill it. T
lymphocytes produce receptors (denoted by TCR) which function as antibodies
produced by B-cells. MHC-loci meta-programs produce Mhc proteins (operations); a Mhc operation
to T- cell receptors and in
this way TCR recognizes this
antigen. Each B-cell and T-cell activates only one
meta-program which produce a single Ig
proteine or a single TCR
There are meta-programs in AIP
i. metaprograms V-J-C
(called lambda or kappa light-chain genes) from V gene segments (i.e. from program
modules) and J-C gene
segments; meta-program V-J-C (a
gene) comprises a V gene
segment, a J gene segment and
a C gene segment,
ii. meta-programs V-D-J-C
(called heavy-chain genes) from V gene segments, D gene segments, J gene segments and C gene segments.
Meta-programs V-J-C and V-D-J-C are executed and produce
lambda or kappa light-chain proteins (operations) and heavy-chain
proteins (operations), respectively.
T-cells have similar
meta-programs as B cells.
No meta-program of the AIP
family belong to a nonvertebrate organism.
As said in Introduction, non-vertebrates have not meta-programs of
adaptive immunity. Adaptive immune system is described in B. Lewin
[LEW], 2008, and D.P. Snustad & M.J. Simmons [SMS], 2006.
3. Mutations of
Mutations are operations which transform DNAs and chromosomes; in this
way mutations (operations) may transform an organism system. Below, I
list mutations which may change a non-vertebrate system (s. P. Snustad
& M. Simmons [SMS], 2006, and A. Schurmann [ASC], 2008; http://www.home-a-schurmann.de/eukar.html).
Postreplic-rep-mut: when a
repair scan/procedure detects a damaged DNA (e.g. a thymine dimer in
DNA strand) then it interrupts
the process and restarts the synthesis by using a homologous DNA
strand; the part of the original nucleotide sequence beginning at the
gap is lost (s. [SMS]).
SOS-response-mut: it is a family of procedures
error-prone-repair system) which are applied
when DNAs are heavily damaged; SOS-genes
are activated - they repair and replicate damaged DNAs using related
nucleotide sequences; these replications are not accurate, so
replication errors occur; thus the SOS-response
build gene mutations (s. [SMS]).
Exis-rep-mut : this
excises the damaged bases in DNA; then it fills in the gap by using the
undamaged complementary strand of the DNA; and then it seals the break.
Inversion: a chromosome
segment is detached, flipped around 180°, and reattached to the rest of
the chromosome. It can be induced by X-irradiation, transposable
elements or by mechanical agents.
Recombination: a DNA segment, z, is moved to an other DNA (and
chromosome) in place of a segment, y,
and simultaneously segment y
is moved to the place where segment z
Transpos-elem: there are three
main types of transposable element mutations in eukaryotes:
(or IS elements): an IS element is excised from
chromosome or mitochondria and then inserted into another position at
the same or different DNA, where this element itself controls this
and Tn3 transposons: they are able to copy and insert genes in
- it uses RNA, associated with this transposable element, as a program
and makes-up a sequence of DNA molecules; then it inserts
this sequence into a new chromosome site.
Transduction: it is a mutation
caused by viruses or bacteria - they destroy a cell (i.e.
degrade its DNAs) or transfer non-vertebrate genes into other
genes, or integrate a DNA of a virus or bacterium in a non-vertebrate
Nonsense-mut: it is a mutation
of a termination triplet or it produces termination triplets within
genes; these mutations are often non-functional.
Missense-mut: this mutation
changes a triplet in a gene (i.e. an instruction in a program) so that
it specifies a different aminoacid, and the mutated gene (altered
program) produces altered (at one place) polypeptide.
Suppressor-mut: it is a
mutation in tRNAs that suppresses other mutations (e.g. some nonsense
Induced-mut: they are caused
by physical or chemical agents; radioactive radiations damage and
degenerate DNAs; some such degeneration are repaired by said repair
procedures; a chemical agent can transform non-vertebrate gene only
other non-vertebrate gene, or into a degenerated or damaged
mutation caused by breakage and crossing over of homologous parental
DNA parts and then rejoining some of them in new combinations.
Only mutations of germ-line cells may affect the progeny of an animal.
The same molecular change in a gene fragment in a germ-line cell may
have the following different effects in the progeny, depending on the
function of this gene fragment:
a) if gene is involved in production of a
protein which is not essential for the metabolic
or replication process, then its mutation does not lead to
b) if gene is involved in production of
a protein needed in metabolic, then its mutation
(which does not produce the needed protein) blocks the metabolic
pathway in the progeny;
mutations in gene segments ivolved in a control or replication
procedure (i.e. a meta-program implemented in genes) alter this
procedure (i.e. genes) in most cases to a wrong or non-functional one,
mutations in a gene (meta-program) which is switched off (i.e. it is
not involved in normal living processes of the progeny) do not change
the living processes of the progeny - such mutations can influence the
progeny only if this meta-program (gene) is activated (e.g. by the
mutations of genes involved in a repair procedure (ie. in genes where
this procedure is implemented) alter this procedure, in most cases to a
wrong or non-functional one,
f) mutations caused by
parental-DNA-recombination recombines some parts of homologous DNAs of
two similar non-vertebrate systems in such a way that the resulting
system is too a non-vertebrate system or it is a non-functional one.
Adaptive immunity did not
evolve by random mutations
above listed mutations are all operations by which multicellular
animal progenies can be transformed. Let us note that before
vertebrates arose, there was no meta-program belonging to the AIP family (AIP was empty). Now we may
formulate the problem we are considered with as follows:
could a finite sequence of germinal random mutations transform some
meta-programs implemented in genes of non-vertebrates into
(genes) belonging to the family AIP?
Below I prove that the answer is "no".
Let NVA denotes a multicellular animal
living in time when no animal had a meta-program belonging to AIP.
First, we consider the case when a germinal random mutation of
(b) or (c) or (e) or (f) occured. Thus it is a mutation of a gene
(meta-program) which is not switched off (i.e. it is in an activated
state). By such mutation system NVA
is transformed into a system NVA1.
i. If this mutation is inversion,
recombination, transpos-elem type (a) or (b), missence-mut or
suppressor-mut, then NVA1 is
a non-functional system or it is also a system of type NVA, because these operations
cannot transform a meta-program (or a sequence of instructions)
belonging to NVA into a
meta-program belonging to AIP; but
some of its genes (meta-programs) may be altered to type (d) (i.e. they
have been switched off) or some of switched off genes may have been
switched on (it is they may be activated); the last case is considered
below in (II).
ii. If the mutation is transduction, then NVA1 is either a destroyed system
or it contains only genes or pseudogenes which occur in NVA or bacteria or viruses (in NVA1 some genes may have been
switched off); thus in NVA1 is
no meta-program which belongs to AIP,
so NVA1 is of type NVA. It is possible that some
genes have been activated; this case is considered in (II).
iii. If the mutation is
postreplic-rep-mut, exis-rep-mut or SOS-response-mut, then it leads to
a non -functional or mutated system in which
some meta-programs (genes) may have been switched on (activated);
as explained in (II), the repair procedures activate only meta-programs
which do not belong to AIP.
iv. If the mutation is a nonsense-mut or
induced-mut, then NVA1 is a
destroyed system (with degenerated DNAs) or it is in a damaged state in
which it activates its repair procedures said in (iii).
v. If the mutation is a retrotransposon,
then NVA1 is also a NVA like system (we assume that in
NVA is not a program for
developing a meta-program belonging to AIP).
Some genes may have been activated; this case is considered in (II).
vi. If the mutation is
parental-DNA-recombination, then the system NVA1 contains only meta-programs
consisting of recombined parts of two similar DNA systems; such
meta-programs do not belong to AIP;
thus NVA1 is of type NVA.
Now we concider the case when random mutation is of type (d), i.e.
off sequence of instructions (genes or pseudogenes) have been mutated
and the mutated NVA system
is functioning. Switched off genes and pseudogenes (i.e. sequences of
instructions) mutade randomly and there is no selection as long as
these sequences of instructions are in the switched off state. Sequence
of such mutations do not convert to any functioning program; random
mutations transform a sequence of instructions (a gene or pseudogene)
into non-functional sequence of instructions or non-interpretable
molecule sequence; although, by probability theory, there exist
obtained instruction sequences which are programs; but probability
theory does not model mutations of genes exactly. In our case, one can
only believe that, more than 500 million years ago, sequences of
germinal random mutations of genes or pseudogenes (in inactivated
genes, where selection did not work) led to more than 50 very complex
and integrated meta-programs belonging to the family AIP. The fact that germinal
mutations did not lead to meta-programs of adaptive immunity in
non-vertebrates shows that the said belief is not scientific
Thus, the switched on genes or pseudogenes, derived by above said
mutations, do not store meta-programs from AIP. Thus, the adaptive immune
system did not evolve from accumulated germinal mutations.
T.A. Brown : Genomes3, Garland Science Publishing, (2007).
[KLE] J. Klein : Der
Wirbeltiere und der Ursprung des adaptiven Immunsystems (in German),
Bericht 2003, Max-Plank-Institut fuer Biologie; Tuebingen, Germany 2003.
[LEW] B. Lewin : Genes IX; Jones& Barklert Publ.,
[NEU] J. Neumann: Immunbiologie; Springer
Verlag Berlin Heidelberg; Germany; 2008.
(SCH] A. Schurmann: Multicellular animals
did not evolve from unicellular organisms;
http://www.home-a-schurmann.de/eukar.html , 2008
[SMS] D. P. Snustad & M. J. Simmons; Principles
of Genetics; John Wiley & Sons, Inc., USA (2006).
To the root
Copyright January 23, 2009;
corrected January 27,