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WHY ARE THERE FOUR LETTERS IN DNA CODE?

A. A. Arzamastsev

Department of Physics and Mathematics, Tambov State University

Key Words and Phrases: DNA code; four-letters code; number of letters;
information ingredient minimum.

Abstract: The aminoacid alphabet having 21 characters (twenty of which are aminoacides and one representing stopsignal) is explained by the fact that the DNA code has four letters. There is no explanation so far why DNA code has four letters. We report here that the DNA four- letters code that takes place in information strands of DNA is optimal from the standpoint of cell information ingredient minimum. Such optimality may be achieved for simple DNA only. These facts may serve as an indirect evidence, that it is these DNA that were the "design" object at one of the early stages of biological evolution.

Introduction

As a result of fundamental researches made by Avery, Watson and Crick in a short period of time (1944-1966) the nature and mechanisms of genetical information transfer were discovered [1-5]. This information is known to be written in DNA strands as a sequence of nucleotides. It is read by means of messenger and transfer RNA by triplets (kodones), information being further translated through ribosomes into appropriate aminoacids. The aminoacid alphabet having 21 characters (twenty of which are aminoacides and one representing stopsignal) is explained by the fact that the DNA code has four letters [5,6]. There is no explanation so far why DNA code has four letters. We report here that the DNA four- letters code that takes place in information strands of DNA is optimal from the standpoint of cell information ingredient minimum. Such optimality may be achieved for simple DNA only. These facts may serve as an indirect evidence, that it is these DNA that were the "design" object at one of the early stages of biological evolution.

Basic concepts

It is evident that in most cases of "designing" various objects Nature followed certain principles of optimality which correspond to maximum or minimum of some objective function. To investigate Nature means to find these objective functions. Hence, to understand why the primary biological code is a four-letters code practically means to find such an objective function which achieves its maximum or minimum provided the number of letters is four.
While solving the problem of DNA code optimality one should bear in mind its primary alphabet, i.e. four- letters alphabet of DNA, rather than 21- letters aminoacid alphabet which is the result of a translation.
When it is necessary to choose the way of recording information one has to decide either in favour of a small or a large number of letters in the alphabet (n). The first alternative simplifies the decoding information machine but leads to lengthy information strands. The latter, on the contrary, shortens the length of a strand but complicates the information machine. The total result of such optimization (compromise) is obtaining minimal value of one of the parameters of information ingredient (for example, volume). This ingredient is the sum of the corresponding parameters of the decoding machine and the programme itself.
Nature might have followed similar principles creating "information ingredient" of simple biological objects at one of the early stages of biological evolution. For the first time this concept was described [7].

Results and discussion

In all probability Nature tends to decrease the part of the cell information ingredient. Thus the volume of the cell remaining the same, the greater part of the cell can be utilized for useful purposes. Indeed from the standpoint of the Present, information media has not any special meaning, it is just used to transfer information from the Present to Future. This statement is well illustrated by Table 1, which shows that the increase of organisms complexity results in the decrease of the part of cells information media [8-10].

Table 1

The information ingredient value for various bioobjects

Bioobject

Part of total mass of a cell, %

 

DNA

RNA

Viruses

5-64

5-32

Bacterial cell

1

6

Mammalian cell

0.25

1.1


To prove this let us suppose that a cell has to code a number of various possibilities (N) into information strand. If for this purpose the cell chooses n- letters alphabet, then the length of the information strand (the number of letters in the programme) will be calculated according to the equation:

L = logn(N) = ln(N)/ln(n)

(1)

If the programme has a cylindrical form, the length of one letter being lc and radius r, which are characteristic of the secondary DNA structure, then the whole information strand will have the following volume:

Vi = r2lcln(N)/ln(n)

(2)

It is also evident that the increase of n results in the increase of the complexity of the decoding information machine and therefore in the increase of its volume, i.e.:

Vm = kn

(3)

where k- is a certain constant of the proportionality. So, the total volume of a cell information ingredient is:

V = Vi + Vm = r2lcln(N)/ln(n) + kn + C,

(4)

where C- is a certain constant which is a total volume of all the elements not depending on n (for example, the volume of protein factors, membrane structures, etc.).
Fig.1 (a,b) shows the qualitative dependence of Vi and Vm on n (equation (4)). One can see that dependence Vi(n) is decreasing, while Vm(n) is increasing, so that the summarized dependence V(n) is unimodal having its minimum (fig.1 c).
To show the minimum of the summarized volume of cell information ingredient takes place at n=4, we identify parameters and coefficients of equations (1)-(4) on the basis of known data, so that equation (4) would be the function of one variable (n) only. From the secondary DNA structure (the radius of the cylinder approximates 1 nm and the length of one nucleotide amounts to 0.34 nm) it follows that lc=0.34.10-9 m and r=10-9 m [6,11]. Since the information machine of a cell is the ribosome, the linear dimension of which

Fig.1. Dependences of the volumes Vi (a), Vm (b) and the total volume of cell information ingredient V (c) (according to ordinate axis), on the number of letters in an alphabet- n (according to abscice axis) when k=1 and r2lcln(N)=1 are fixed.
approximates 1.8.10-8 m and its volume is 3.10-24 m3 [8,11] we find for n=4 that k=V/n=0.75.10-24.
Then

V(n) = r2lcln(N)/ln(n) + kn + C =
3.14.10-18.0.34.10-9.ln(N)/ln(n)+ 0.75.10-24.n + C =
[10-3.ln(N)/ln(n)+0.75.n].10-24 + C


(5)

The function presented by equation (5) has its minimum if the expression in square brackets is minimal. Let us find n at which the value of the expression is minimal. For this purpose we determine the derivative dV/dn and compare it to zero.

dV/dn = -10-3.ln(N)/{n.ln2(n)} + 0.75 = 0

(6)

The latter equation may be solved by numerical methods only. The result of computer calculation will be n=4 if ln(N)= 5765.4.
Hence it is possible that designing the molecular mechanism of information transfer, Nature might have attempted to do it in the most compact form, solving in this way the problem of monodimensional optimization.
It is worth discussing here the value of ln(n). It should be noted that N is a summarized number of possibilities coded in the genome. It is easy to show that the derived value of ln(n) corresponds to the length of the DNA strand which approximates 4200 nucleotide pairs (letters). The programme of such a length is characteristic of the simplest organisms, mitochondrial DNA and some viruses.
Table 2 presents certain values of information strand length known from modern biology, ln(N), and optimal number of letters in the alphabet (found from equation (6)), characteristic of various living organisms. The table shows that the optimal number of letters in the alphabet (n=4) corresponds only to the simplest forms of life and DNA. For more complex organisms the value of n is one or several orders greater.
If the above mentioned arguments are correct, it means that the "design" situation of DNA code by Nature is surprisingly analogous to that of designing computers by a human being. If the first computers had been constructed nowadays, the binary notation system might not have been used. It was chosen at the early stage in order to simplify as much as possible the design of the decoding machine. It is too late to correct this mistake now. Probably an identical "miscalculation" was made by Nature, while designing living organisms. In any case, the analogy is evident.
To be more illustrative Fig.2 shows the dependence analogous to that described in Fig.1, however built in accordance with the real parameters and coefficients obtained in the course of calculations. This figure clearly shows that the values of the summarized volume V corresponding to the values of n equal to 3,4 and 5 are located approximately

Table 2

Optimal number of letters in the alphabet for various living organisms

Living organisms

Length of DNA strand, bases or base pairs

Ln(N)

O Optimal number of letters in the alphabet

Homo

3.109

4.2.109

47780

Strongylocentrotus purpuratus

8.108

1.1.109

15828

Drosophila melanogaster

1.6.108

2.2.108

4242

Saccharomyces cerevisiae

1.35.107

1.9.107

607

Escherichia coli

4.106

5.6.106

245

Bacteriophage

48502

6.7.104

13

Bacterial virus X174

5386

7.5.103

4

Hypothetical bioobject with base strand length equal to 4159

4159

5.8.103

4

 


Fig.2. The minimum value of the total volume of information ingredient for simple cells is obtained at n=4, however, n=3 and n=5 can claim for minimum too.

 

on the same level. It means that the sensibility of V to n at n equal to 3 - 5 is extremely low. That is why Nature might have chosen any value of n from this domain. The choice of Nature in favour of n=4 permits to get an additional degree of freedom, slightly changing the length of DNA strand without influencing the total optimality. Thus, at parameters values referred to in this article, the minimal values of equations (4) and (5) are obtained at n=4 (provided that n- is an integer), if the length of DNA strand varies within a wide range, from 3110 up to 5400 bases or base pairs.

Thus, we have demonstrated that four- letters code which takes place in information DNA strands is optimal from the standpoint of the summarized volume minimum of the cell information ingredient. This optimality is relevant for the simplest DNA only.

This indirectly proves that the simplest DNA (rather than more complex ones) were the object of "design" at one of the early stages of biological evolution.

References

  1. Avery O.T., MacLeod C.M. & MacCarty M. J. Exp. Med. 79,137158 (1944).
  2. Watson J.D. & Crick F.H.C. Nature. 171, 737-738 (1953).
  3. Watson J.D. & Crick F.H.C. Nature. 171, 964-967 (1953).
  4. Watson J.D. & Crick F.H.C. Cold Spring Harbor Symp. Quant. Biol. 18, 123-131 (1953).
  5. Crick F.H.C. Sci. Am. 215, 55-62 (1966).
  6. Watson J.D., Tooze J. & Kurtz D.T. Recombinant DNA. Scientific American Books. Distributed by W.H. Freeman and Company, New York, (1983).
  7. Arzamastsev A.A. Zhurnal Obshchei Biologii. 56, 405-410 (1995) in Russian and English translation.
  8. Alberts B., Bray D., Lewis J., Raff M., Roberts K. & Watson J.D. Molecular Biology of the Cell. Garland Publishing, Inc. New York, London, (1983).
  9. Sengbusch P. Molekular - und Zellbiologie. Springer-Verlag, Berlin, Heidelberg, New York, (1979).
  10. Musil J., Novakova O., Kunz K. Biochemistry in schematic perspective. Czechoslovak Medical Press, Prague, (1980).
  11. Volkenstein M.V. Biophysika . Nauka, Moscow, (1988).

ACKNOWLEDGEMENTS. I thank A.V. Troizki (Moscow State University) and Y.I. Golovin (Tambov State University) for discussion, N.L. Niculshina for revision in English. This work was partially supported by Mr. George Soros International Science Foundation (grant 4707-3) and International Soros Science Education Program (grant D346).

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