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# PURINE-PYRIMIDINE SYMMETRY, DETERMINATIVE DEGREE AND DNA

## Abstract

Various symmetries connected with purine-pyrimidine content of DNA sequences are studied in terms of the intruduced determinative degree, a new characteristics of nucleotide which is connected with codon usage. A numerological explanation of CG pressure is proposed. A classification of DNA sequences is given. Calculations with real sequences show that purine-pyrimidine symmetry increases with growing of organization. A new small parameter which characterizes the purine-pyrimidine symmetry breaking is proposed for the DNA theory.

Abstract investigation of the genetic code is a powerful tool in DNA models construction and understanding of genes organization and expression . In this direction the study of symmetries , application of group theory  and implication of supersymmetry  are the most promising and necessary for further elaboration. In this paper we consider symmetries connected with purine-pyrimidine content of DNA sequences in terms of the determinative degree introduced in .

We denote a triplet of nucleotides by $`xyz`$, where $`x,y,z=𝐂,𝐓,𝐀,𝐆`$. Then redundancy means that an amino acid is fully determined by first two nucleotides $`x`$ and $`y`$ independently of third $`z`$ . Sixteen possible doublets $`xy`$ group in 2 octets by ability of amino acid determination . Eight doublets have more “strength” in sense of the fact that they simply encode amino acid independently of third bases, other eight (“weak”) doublets for which third bases determines content of codons. In general, transition from the “powerful” octet to the “weak” octet can be obtained by the exchange  $`𝐂\stackrel{}{}𝐀,𝐆\stackrel{}{}𝐓`$, which we name “star operation $`()`$” and call purine-pyrimidine inversion. Thus, if in addition we take into account GC pressure in evolution  and third place preferences during codon-anticodon pairing , then 4 nucleotides can be arranged in descending order in the following way:

$$\begin{array}{cccc}\text{Pyrimidine}& \text{Purine}& \text{Pyrimidine}& \text{Purine}\\ 𝐂& 𝐆& 𝐓& 𝐀\\ \text{very “strong”}& \text{“strong”}& \text{“weak”}& \text{very “weak”}\end{array}$$
(1)
Now we introduce a numerical characteristics of the empirical “strength” — determinative degree $`𝐝_x`$ of nucleotide $`x`$ and make transition from qualitative to quantitative description of genetic code structure . It is seen from (1) that the determinative degree of nucleotide can take value $`𝐝_x=\mathrm{𝟏},\mathrm{𝟐},\mathrm{𝟑},\mathrm{𝟒}`$ in correspondence of increasing “strength”. If we denote determinative degree as upper index for nucleotide, then four bases (1) can be presented as vector-row $`𝕍=\left(\begin{array}{cccc}𝐂^{\left(\mathrm{𝟒}\right)}& 𝐆^{\left(\mathrm{𝟑}\right)}& 𝐓^{\left(\mathrm{𝟐}\right)}& 𝐀^{\left(\mathrm{𝟏}\right)}\end{array}\right)`$. Then the exterior product $`𝕄=𝕍\times 𝕍`$ represents the doublet matrix $`𝕄`$ and corresponding rhombic code , and the triple exterior product $`𝕂=𝕍\times 𝕍\times 𝕍`$ corresponds to the cubic matrix model of the genetic code which were described in terms of the determinative degree in . To calculate the determinative degree of doublets $`xy`$ we use the following additivity assumption

$$𝐝_{xy}=𝐝_x+𝐝_y,$$
(2)
which holds for triplets and for any nucleotide sequence. Then each of 64 elements (codons) of the cubic matrix $`𝕂`$ will have a novel number characteristics —determinative degree of codon $`𝐝_{xyz}=𝐝_{codon}=𝐝_x+𝐝_y+𝐝_z`$ which takes value in the range $`\mathrm{𝟑}÷\mathrm{𝟏𝟐}`$. We can also define the determinative degree of amino acid $`𝐝_{\mathrm{𝖠𝖠}}`$ as mean arithmetic value $`𝐝_{\mathrm{𝖠𝖠}}=𝐝_{codon}/n_{deg}`$, where $`n_{deg}`$ is its degeneracy (redundancy). That can allow us to analyze new abstract amino acid properties in connection with known biological properties .

Let us consider a numerical description of an idealized DNA sequence as a double-helix of two codon strands connected by complementary conditions . Each strand is described by four numbers $`(n_𝐂,n_𝐆,n_𝐓,n_𝐀)`$ and $`(m_𝐂,m_𝐆,m_𝐓,m_𝐀)`$, where $`n_x`$ is a number of nucleotide $`x`$ in one strand. In terms of $`n_x`$ and $`m_x`$ the complementary conditions are

$$n_𝐂=m_𝐆,m_𝐂=n_𝐆,n_𝐓=m_𝐀,m_𝐓=n_𝐀.$$
(3)
The Chargaff’s rules  for a double-helix DNA sequence sound as: 1) total quantity of purines and pyrimidines are equal $`N_𝐀+N_𝐆=N_𝐂+N_𝐓`$; 2) total quantity of adenine and cystosine equal to total quantity of guanine and thymine $`N_𝐀+N_𝐂=N_𝐓+N_𝐆`$; 3) total quantity of adenine equal to total quantity of thymine $`N_𝐀=N_𝐓`$ and total quantity of cystosine equal to total quantity of guanine $`N_𝐂=N_𝐆`$; 4) the ratio of guanine and cystosine to adenine and thymine $`v=\left(N_𝐀+N_𝐓\right)/\left(N_𝐂+N_𝐆\right)`$ is approximately constant for each species. Usually the Chargaff’s rules are defined through macroscopic molar parts which are proportional to absolute number of nucleotides in DNA . If we consider a DNA double-helix sequence, then $`N_x=n_x+m_x`$. In terms of $`n_x`$ and $`m_x`$ the first three Chargaff’s rules lead to the equations which are obvious identities, if complimentary (3) holds. From fourth Chargaff’s rule it follows that the specificity coefficient $`v_{nm}`$ for two given strands is

$$v_{nm}=\frac{n_A+m_𝐀+n_𝐓+m_𝐓}{n_𝐂+m_𝐂+n_𝐆+m_𝐆}.$$
(4)
The complementary (3) leads to the equality of coefficients $`v`$ of each strand $`v_{nm}=v_n=v_mv`$, and $`v`$ is connected with GC content $`p_{\mathrm{𝐂𝐆}}`$ in the double-helix DNA as $`p_{\mathrm{𝐂𝐆}}=1/\left(1+v\right)`$.

We consider another important coefficient: the ratio of purines and pyrimidines $`k`$. For two strands from the first Chargaff’s rule we obviously derive $`k_{nm}=1`$. But for each strand we have

$$k_n=\frac{n_𝐆+n_𝐀}{n_𝐂+n_𝐓},k_m=\frac{m_𝐆+m_𝐀}{m_𝐂+m_𝐓}$$
(5)
which satisfy the equation $`k_nk_m=1`$ following from complementary.

Let us introduce the determinative degree of each strand exploiting the additivity assumption (2) as

$`𝐝_n`$ $`=`$ $`\mathrm{𝟒}n_𝐂+\mathrm{𝟑}n_𝐆+\mathrm{𝟐}n_𝐓+\mathrm{𝟏}n_𝐀,`$ (6)
$`𝐝_m`$ $`=`$ $`\mathrm{𝟒}m_𝐂+\mathrm{𝟑}m_𝐆+\mathrm{𝟐}m_𝐓+\mathrm{𝟏}m_𝐀.`$ (7)
The values $`𝐝_n`$ and $`𝐝_m`$ can be viewed as characteristics of the empirical “strength” for strands, i.e. “strand generalization” of (1). Then we define summing and difference “strength” of a double-helix sequence by

$$𝐝_+=𝐝_n+𝐝_m,𝐝_{}=𝐝_n𝐝_m.$$
(8)
The first variable $`𝐝_+`$ can be treated as the summing empirical “strength” of DNA (or its fragment). Taking into account the complementary conditions (3) we obtain $`𝐝_+`$ through one strand variables

$$𝐝_+=\mathrm{𝟕}\left(n_𝐂+n_𝐆\right)+\mathrm{𝟑}\left(n_𝐓+n_𝐀\right).$$
(9)
We can also present $`𝐝_+`$ through macroscopically determined variables $`N_x`$ as follows $`𝐝_+=\mathrm{𝟕}N_𝐂+\mathrm{𝟑}N_𝐀=\mathrm{𝟕}N_𝐆+\mathrm{𝟑}N_𝐓`$, or through GC and AT contents as $`𝐝_+={\displaystyle \frac{\mathrm{𝟕}}{2}}N_{𝐂+𝐆}+{\displaystyle \frac{\mathrm{𝟑}}{2}}N_{𝐀+𝐓}`$.

To give sense to the difference $`𝐝_{}`$ we derive

$$𝐝_{}=n_𝐂+n_𝐓n_𝐆n_𝐀.$$
(10)
We see that the star operation obviously acts as $`\left(𝐝_+\right)^{}=𝐝_+`$ and $`\left(𝐝_{}\right)^{}=𝐝_{}`$. From (9)-(10) it follows the main statement:

> The biological sense of the determinative degree $`𝐝`$ is contained in the following purine-pyrimidine relations:
>
> 1) The sum of the determinative degrees of matrix and complementary strands in DNA (or its fragment) equals to
>
> $$𝐝_+=\frac{\mathrm{𝟕}}{2}N_{𝐂+𝐆}+\frac{\mathrm{𝟑}}{2}N_{𝐀+𝐓}.$$
> (11)
> 2) The difference of the determinative degrees between matrix and complementary strands in DNA (or its fragment) exactly equals to the difference between pyrimidines and purines in one strand
>
> $$𝐝_{}=n_{pyrimidines}n_{purines},$$
> (12)
> where $`n_{pyrimidines}=n_𝐂+n_𝐓`$ and $`n_{purines}=n_𝐆+n_𝐀`$, or it is equal to difference of purines or pyrimidines between strands
>
> $$𝐝_{}=n_{pyrimidines}m_{pyrimidines}=m_{purines}n_{purines}.$$
> (13)

We can also find connection between $`𝐝_+,𝐝_{}`$ and the coefficients $`k`$ and $`v`$ as follows

$`𝐝_+`$ $`=`$ $`{\displaystyle \frac{1}{2}}N_{𝐂+𝐆}\left(7+3v\right)=N_{𝐂+𝐆}\left(2+{\displaystyle \frac{3}{2p_{\mathrm{𝐂𝐆}}}}\right),`$ (14)
$`𝐝_{}`$ $`=`$ $`n_{pyrimidines}\left(1k_n\right).`$ (15)
If we consider one species for which $`v=const`$ (or $`p_{\mathrm{𝐂𝐆}}=const`$), then we observe that $`𝐝_+N_{𝐂+𝐆}`$, which can allow us to connect the determinative degree with ”second level” of genetic information . From another side, the ratio $`{\displaystyle \frac{7}{3}}`$ of coefficients in (11) can play a numerological role in CG pressure explanations , and therefore $`𝐝_+`$ can be considered as some kind of “evolutionary strength”.

Now we consider the determinative degree of double-helix sequences in various extreme cases and classify them. We call a DNA sequence mononucleotide, dinucleotide, trinucleotide or full, if one, two, three or four numbers $`n_x`$ respectively distinct from zero. Properties of mononucleotide double-helix DNA sequence are in the Table 1.

Table 1. Mononucleotide DNA

| $`n_x`$ | $`𝐝_+`$ | $`𝐝_{}`$ | amino acid |
| --- | --- | --- | --- |
| $`n_𝐂0`$ | $`7n_𝐂`$ | $`n_𝐂`$ | Pro |
| $`n_𝐆0`$ | $`7n_𝐆`$ | $`n_𝐆`$ | Gly |
| $`n_𝐓0`$ | $`3n_𝐓`$ | $`n_𝐓`$ | Phe |
| $`n_𝐀0`$ | $`3n_𝐀`$ | $`n_𝐀`$ | Lis |

The mononucleotide sequences which encode most extended amino acids Gly and Lis have negative $`𝐝_{}`$, and the mononucleotide sequences which encode amino acids Pro and Phe with similar chemical type of radicals have positive $`𝐝_{}`$.

The dinucleotide double-helix DNA sequences (without mononucleotide parts) are described in the Table 2.

Table 2. Dinucleotide DNA

| $`n_x`$ | $`𝐝_+`$ | $`𝐝_{}`$ | amino acid |
| --- | --- | --- | --- |
| $`n_𝐂0,n_𝐆0`$ | $`7\left(n_𝐂+n_𝐆\right)`$ | $`n_𝐂n_𝐆`$ | Pro,Arg,Ala,Gly |
| $`n_𝐂0,n_𝐓0`$ | $`7n_𝐂+3n_𝐓`$ | $`n_𝐂+n_𝐓`$ | Pro,Phe,Leu,Ser |
| $`n_𝐂0,n_𝐀0`$ | $`7n_𝐂+3n_𝐀`$ | $`n_𝐂n_𝐀`$ | Pro,Gly,Asn,Tur,His |
| $`n_𝐆0,n_𝐓0`$ | $`7n_𝐆+3n_𝐓`$ | $`n_𝐓n_𝐆`$ | Gly,Leu,Val,Cys,Trp |
| $`n_𝐆0,n_𝐀0`$ | $`7n_𝐆+3n_𝐀`$ | $`n_𝐆n_𝐀`$ | Gly,Glu,Arg,Lys |
| $`n_𝐓0,n_𝐀0`$ | $`3\left(n_𝐓+n_𝐀\right)`$ | $`n_𝐓n_𝐀`$ | Leu,Asn,Tur,TERM |

The trinucleotide DNA can be listed in the similar, but more cumbersome way. The full DNA sequences consist of nucleotides of all four types and described by (9)-(10).

The introduction of the determinative degree allows us to single out a kind of double-helix DNA sequences which have an additional symmetry. We call a double-helix sequence purine-pyrimidine symmetric, if

$$𝐝_{}=0,$$
(16)
i.e. its empiric “strength” vanishes. From (10) it follows

$$n_𝐂+n_𝐓=n_𝐆+n_𝐀,$$
(17)
i.e. $`k_n=k_m=1`$, which can be rewritten for one strand

$$n_{pyrimidines}=n_{purines}$$
(18)
or as equality of purines and pyrimidines in two strands

$`n_{pyrimidines}`$ $`=`$ $`m_{pyrimidines},`$ (19)
$`n_{purines}`$ $`=`$ $`m_{purines}.`$ (20)
The purine-pyrimidine symmetry (17) has two particular cases:

$`1)\begin{array}{c}n_𝐂=n_𝐆,\\ n_𝐓=n_𝐀,\end{array}\text{symmetric DNA,}`$ (23)
$`2)\begin{array}{c}n_𝐂=n_𝐀,\\ n_𝐓=n_𝐆,\end{array}\text{antisymmetric DNA.}`$ (26)
The first case corresponds to the Chargaff’s rule applied to a single strand which approximately holds for long sequences , and so it would be interesting to compare transcription and expression properties of symmetric and antisymmetric double-helix sequences.

We have made a preliminary analysis of real sequences of several species taken from GenBank (2000) in terms of the determinative degree. It were considered 10 complete sequences of E.coli (several genes and full genomic DNA 9-12 min.), 12 complete sequences of Drosophila melanogaster (crc genes), 10 complete sequences of Homo sapiens Chromosome 22 (various clones), 10 complete sequences of Homo sapiens Chromosome 3 (various clones). We calculated the nucleotide content $`N_𝐂,N_𝐓,N_𝐆,N_𝐀`$ and the determinative degree characteristics $`𝐝_+,𝐝_{},q=𝐝_{}/𝐝_+,k_n`$ and $`v`$ for every sequence. Then we averaged their values for each species. The result is presented in the Table 3.

Table 3. Mean determinative degree characteristics of real sequences

| sequence | $`{\displaystyle \frac{1}{n}}𝐝_+`$ | $`{\displaystyle \frac{1}{n}}𝐝_{}`$ | $`{\displaystyle \frac{1}{n}}q10^3`$ | $`{\displaystyle \frac{1}{n}}k_n`$ | $`{\displaystyle \frac{1}{n}}v`$ |
| --- | --- | --- | --- | --- | --- |
| E.coli | 90806 | -138 | -6.8 | 1.07 | 1.38 |
| Drosophila | 7325 | -70 | -8.9 | 1.09 | 1.31 |
| Homo sap. Chr.22 | 337974 | 6865 | 1.46 | 0.987 | 1.14 |
| Homo sap. Chr.3 | 806435 | -1794 | -2.29 | 1.021 | 1.55 |

First of all we observe that all real sequences have high purine-pyrimidine symmetry (smallness of parameter $`q`$). Also we see that the relation of purines and pyrimidines in one DNA strand $`k_n`$ is very close to unity, therefore we have a new small parameter in the DNA theory $`\left(k_n1\right)`$ (or $`q`$), which characterizes the purine-pyrimidine symmetry breaking. This can open possibility for various approximate and perturbative methods application. Second, we notice from Table 3 that the purine-pyrimidine symmetry increases in direction from protozoa to mammalia and is maximal for human chromosome. It would be worthwhile to provide a thorough study of purine-pyrimidine symmetry and codon usage in terms of the introduced determinative degree by statistical methods, which will be done elsewhere.

Acknowledgments. Authors would like to thank G. Shepelev for providing with computer programs, S. Gatash, V. Maleev and O. Tretyakov for fruitful discussions and J. Bashford, G. Findley and P. Jarvis for useful correspondence and reprints.