<?xml version="1.0" encoding="utf8"?>
 <!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.0 20120330//EN" "http://jats.nlm.nih.gov/publishing/1.0/JATS-journalpublishing1.dtd"> <article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" article-type="review-article" dtd-version="1.0" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JGE</journal-id>
      <journal-title-group>
        <journal-title>Journal of Genetic Engineering</journal-title>
      </journal-title-group>
      <issn pub-type="epub">2694-1198</issn>
      <publisher>
        <publisher-name>Open Access Pub</publisher-name>
        <publisher-loc>United States</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="doi">10.14302/issn.2694-1198.jge-20-3515</article-id>
      <article-id pub-id-type="publisher-id">JGE-20-3515</article-id>
      <article-categories>
        <subj-group>
          <subject>review-article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Genetic-Mathematical Modelling of the Populations Interaction</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>A.N.</surname>
            <given-names>Volobuev</given-names>
          </name>
          <xref ref-type="aff" rid="idm1842936588">1</xref>
          <xref ref-type="aff" rid="idm1842934644">*</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1842936588">
        <label>1</label>
        <addr-line>Samara State Medical University. Department of Medical Physics. Samara, Russia </addr-line>
      </aff>
      <aff id="idm1842934644">
        <label>*</label>
        <addr-line>Corresponding author</addr-line>
      </aff>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Yu</surname>
            <given-names>Xiong</given-names>
          </name>
          <xref ref-type="aff" rid="idm1843061220">1</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1843061220">
        <label>1</label>
        <addr-line>Associate Professor Vice presedent of Chongqing Association of Prosthodontics, China.</addr-line>
      </aff>
      <author-notes>
        <corresp>
    
    A.N. Volobuev, <addr-line>Samara State Medical University, Department of Medical </addr-line><addr-line>Physics,   </addr-line><addr-line>          Samara, Russia,</addr-line> Email:  <email>volobuev47@yandex.ru</email></corresp>
        <fn fn-type="conflict" id="idm1843245692">
          <p>The authors have declared that no competing interests exist.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub" iso-8601-date="2020-09-01">
        <day>01</day>
        <month>09</month>
        <year>2020</year>
      </pub-date>
      <volume>1</volume>
      <issue>2</issue>
      <fpage>1</fpage>
      <lpage>8</lpage>
      <history>
        <date date-type="received">
          <day>15</day>
          <month>08</month>
          <year>2020</year>
        </date>
        <date date-type="accepted">
          <day>27</day>
          <month>08</month>
          <year>2020</year>
        </date>
        <date date-type="online">
          <day>01</day>
          <month>09</month>
          <year>2020</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>© </copyright-statement>
        <copyright-year>2020</copyright-year>
        <copyright-holder>A.N. Volobuev</copyright-holder>
        <license xlink:href="http://creativecommons.org/licenses/by/4.0/" xlink:type="simple">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
        </license>
      </permissions>
      <self-uri xlink:href="http://openaccesspub.org/jge/article/1443">This article is available from http://openaccesspub.org/jge/article/1443</self-uri>
      <abstract>
        <p>The solution of a genetic-mathematical problem of interaction of the human population cells and virus    population to a problem of pandemic COVID-19 is submitted. The mathematical model based on the Hardy - Weinberg law consisting of two interdependent differential equations is used. The equations reflect time dynamics of the human cells and virus populations during their interaction. Solutions of the differential equations are found and results of these solutions are analyzed. The estimation of duration pandemic is received at use of parameters of the human liver cells and a flu virus.</p>
      </abstract>
      <kwd-group>
        <kwd>Hardy - Weinberg law</kwd>
        <kwd>cells</kwd>
        <kwd>viruses</kwd>
        <kwd>time of a life</kwd>
        <kwd>duration of pandemic.</kwd>
      </kwd-group>
      <counts>
        <fig-count count="2"/>
        <table-count count="0"/>
        <page-count count="8"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec id="idm1842804084" sec-type="intro">
      <title>Introduction</title>
      <p>Occurrence in the world of the pandemic   COVID-19 has put a number of scientific and technical problems. First of all it is a practical problem of creation of a vaccine against of coronavirus. Does not cause doubt that this problem will be successfully solved in the near future since for creation of a vaccine the many science laboratories in the advanced countries work, and sufficient finance for researches are allocated. </p>
      <p>However there were also other problems. In particular there is interest the forecast as a long time can last the pandemic, what global consequences will arise owing to propagation of disease. Not applying for exhaustive answers to the given questions, we shall notice that the problem of definition of the pandemic duration can be in part solved on the basis of                genetic-mathematical modeling process of the two population interaction: human and virus.</p>
      <p>First of all we shall note that the virus population cooperates not with a human population as set of very complex organisms, and with a population of separate cells of an organism. The death of the person at virus attack is exclusive enough event though on death rate estimate propagation for example of coronavirus infections, success of counteraction to it.</p>
      <p>As a result of interaction of a virus and aт organism cell the cell can be perish that usually does not result to death of an organism as a whole. During interaction there can be perish a virus owing to functioning immune system of the person, occurrence of antibodies to a virus antigene.</p>
      <p>At modeling a problem of a virus and an organism cell interaction arises two problems. First, it is necessary is genetically proved to model influence of the first population (human or is more exact cellular) on the second population (virus) and the second population on the first. Naturally these influences can be carried out under different laws. Second, it is necessary to take into account a various time scale for both populations since average time of a life of the human cells can differ from average time of a life of viruses essentially. These factors do the solution of a problem of the populations interaction enough complex.</p>
      <sec id="idm1842802428">
        <title>Hardy – Weinberg law for cooperating populations</title>
        <p>If there is some mutagen factor D<sub>2,1</sub> working from the second population on first population the law of Hardy - Weinberg for the first population it is possible to write down as <xref ref-type="bibr" rid="ridm1842899164">1</xref><xref ref-type="bibr" rid="ridm1842968316">2</xref>:</p>
        <p><inline-graphic xlink:href="images/image1.jpeg" mime-subtype="jpeg"/>       .......(1)</p>
        <p>Where q <sub>f</sub><sub>1</sub>  there is frequency of recessive female allele of the first population subjected to influence from the second population. As the first population we consider cells of the person organism for example cells of a liver. Dimensionless time n<sub>1</sub>=t/T<sub>1</sub> , where T<sub>1</sub> - average time of a life of organism cells for an individual of the first population. For cells of a liver on different sources is T<sub>1</sub> ≈ 140days  <xref ref-type="bibr" rid="ridm1842983004">3</xref><xref ref-type="bibr" rid="ridm1843000172">4</xref><xref ref-type="bibr" rid="ridm1842760172">5</xref>.</p>
        <p>The Hardy - Weinberg law for the second population we shall write down similarly:</p>
        <p><inline-graphic xlink:href="images/image2.jpeg" mime-subtype="jpeg"/>  ......(2)</p>
        <p>At writing of the equation (2) we have assumed that in the second population there is no division into male and female individuals, so Q<sub>2</sub>  there is a frequency of recessive allele which is subjected to influence in genome of the second population. For example, such situation is characteristic for bacterial, microbic or virus populations. Dimensionless time n<sub>2</sub>=t/T<sub>2</sub>, where T<sub>2</sub>  there is average time of an individual life of the second population. For example, for a virus of flu is  T<sub>2</sub>≈ 7 days <xref ref-type="bibr" rid="ridm1842983004">3</xref><xref ref-type="bibr" rid="ridm1843000172">4</xref><xref ref-type="bibr" rid="ridm1842760172">5</xref>. The mutagen factor working on immune system of the first population on second, is designated D<sub>1,2</sub>.</p>
        <p>Let's enter uniform dimensionless time. From a condition n<sub>1</sub>T<sub>1</sub> = n<sub>2</sub>T<sub>2</sub>  we find n<sub>2</sub>=(T<sub>1</sub>/T<sub>2</sub>)n<sub>1</sub>=(1/γ)n<sub>1</sub></p>
        <p>where a constant γ = T<sub>2</sub>/T<sub>1</sub>≈0,05 Hence the equation (2) can be copied as:</p>
        <p><inline-graphic xlink:href="images/image3.jpeg" mime-subtype="jpeg"/>         …..(3)</p>
        <p>Let's examine the mutagen factors. We shall assume that allele in genome of the second population q<sub>2</sub> at interaction with the first population it is inserted in a genome of the first population with catastrophic for a cell of the first population consequences. Hence, it is possible to assume that the mutagen factor is  D<sub>2,1</sub>=α<sub>1</sub>q<sub>2</sub> where α<sub>1</sub>&lt;0 there is some constant factor.</p>
        <p>Influence of the first population on the second consists in destruction by immune system of the first population of individuals (viruses) of the second population. Hence, it is possible to assume that D<sub>1,2</sub> = α<sub>2</sub>, and size  α<sub>2</sub>&lt;0.</p>
        <p>Thus the equations (1) and (3) get a kind:</p>
        <p><inline-graphic xlink:href="images/image4.jpeg" mime-subtype="jpeg"/>   ...(4)</p>
        <p><inline-graphic xlink:href="images/image5.jpeg" mime-subtype="jpeg"/>.....(5)</p>
        <p>In the equations (4) and (5) index at dimensionless time is omitted since transition by uniform dimensionless time n=n<sub>1</sub>  was carried out.</p>
      </sec>
      <sec id="idm1842770820">
        <title>Development of a Virus population During Time of Pandemic</title>
        <p>The equation (5) for the second (virus) population at influence on it of the first population immune system can be solved irrelatively of the equations (4).</p>
        <p>We integrate once the equation (5):</p>
        <p><inline-graphic xlink:href="images/image6.jpeg" mime-subtype="jpeg"/>    .....(6)</p>
        <p>Where C<sub>1</sub>  there is a constant of integration.</p>
        <p>For the solution of the equation (6) we shall present function q<sub>2</sub>  as product of two functions q<sub>2</sub>=uv . Then the equation (6) will be copied as:</p>
        <p><inline-graphic xlink:href="images/image7.jpeg" mime-subtype="jpeg"/>…..(7)</p>
        <p>Grouping the terms we shall find:</p>
        <p><inline-graphic xlink:href="images/image8.jpeg" mime-subtype="jpeg"/>                            ....(8)</p>
        <p>Expression in brackets we shall accept equal to zero γdu/dn+ln2u=0. Integrating this equality we shall find ln<italic>u</italic><italic>=-ln2n/</italic>γ=-ln2<sup>n/</sup><sup>γ</sup> . Hence there is u=2<sup>-</sup><sup>n/γ</sup>. A constant of integration it is accepted equal to zero since there is some arbitrariness in a choice of function<italic> u</italic>. Substitute this function in (8) we shall receive:</p>
        <p><inline-graphic xlink:href="images/image9.jpeg" mime-subtype="jpeg"/>          .....(9)</p>
        <p>Solving the equation (9) concerning function V we find:</p>
        <p><inline-graphic xlink:href="images/image10.jpeg" mime-subtype="jpeg"/>         .....(10)</p>
        <p>Hence:</p>
        <p><inline-graphic xlink:href="images/image11.jpeg" mime-subtype="jpeg"/>  …..(11)</p>
        <p>Thus for allele frequency q<sub>2</sub> we shall find:</p>
        <p><inline-graphic xlink:href="images/image12.jpeg" mime-subtype="jpeg"/>       ....(12)</p>
        <p>We use the following conditions: at n=0 the allele frequency is q<sub>2</sub> = q<sub>20</sub>, at n/γ=1/ln2  allele frequency is <inline-graphic xlink:href="images/image13.png" mime-subtype="png"/>. The second condition is equivalent to time t=1.443t<sub>2</sub>, i.e. the second condition is accepted for time approximately in one and a half time more than average time of an individual life of the second population.</p>
        <p>Hence on the first condition:</p>
        <p><inline-graphic xlink:href="images/image14.jpeg" mime-subtype="jpeg"/>  ….(13)</p>
        <p>on the second condition:</p>
        <p><inline-graphic xlink:href="images/image15.jpeg" mime-subtype="jpeg"/>     ….(14)</p>
        <p>Solving the system (13), (14) we find:</p>
        <p><inline-graphic xlink:href="images/image16.jpeg" mime-subtype="jpeg"/>   …...(15)</p>
        <p><inline-graphic xlink:href="images/image17.jpeg" mime-subtype="jpeg"/>….(16)</p>
        <p>Substituting (15) and (16) in (12) we shall receive:</p>
        <p><inline-graphic xlink:href="images/image18.jpeg" mime-subtype="jpeg"/>          ……..(17)</p>
        <p>The formula (17) can be written down as the sum of two terms: reflecting duplication in the second (virus) population and influence on it first population:</p>
        <p><inline-graphic xlink:href="images/image19.jpeg" mime-subtype="jpeg"/>     .....(18)</p>
        <p>Let's note that duplication in a virus population occurs not independently but only at interaction to cells, for example, a human population. Therefore at the first term (18) there is a size γ=T<sub>2</sub>/T<sub>1</sub>  dependent on average time of a cell life of the first (human) population. The second term (18) reflects action of the person immune system on the second (virus) population.</p>
        <p>On <xref ref-type="fig" rid="idm1842808156">Figure 1</xref> change of an allele frequency q<sub>2</sub>  the second (virus) population in time at absence of influence of the person immune system (curve 1), and at presence of influence (curve 2) of the first population immune system is shown.</p>
        <fig id="idm1842808156">
          <label>Figure 1.</label>
          <caption>
            <title> Change of an allele frequency q2 in time for the second (virus) population at absence of influence of the first (human) population immune system, a curve 1 and at presence of                    influence, a curve 2. Parameters for calculation q0 =0,3;; q2=0,65; γ=0,05;α2 = -0.01.</title>
          </caption>
          <graphic xlink:href="images/image20.jpg" mime-subtype="jpg"/>
        </fig>
        <p>From the analysis of graphs it is visible that at absence of influence of a human population immune system on a virus population there is a gradual growth of the allele frequency q<sub>2</sub> in time; the approach of allele frequency  q<sub>2 </sub>to equilibrium value. At presence of influence of the first (human) population immune system the growth q<sub>2</sub> is replaced by falling due to destruction of viruses at action of immune system of the first population.</p>
      </sec>
      <sec id="idm1842747260">
        <title>Development of a Human Population During Time of Pandemic</title>
        <p>The most interesting question it is work of organism cells of a human population at their interaction with viruses. Some results of such interaction can be received at the solution of the equation (4).</p>
        <p>The solution of the equation (4) can be received substitution of the solution (18) in the equation (4). However such way is difficult occurrence of complex function in the right part of the equation (4). Therefore we shall increase the order of the equation having substituted function q<sub>2</sub> from the equation (4) in the equation (5). In result we shall receive the linear differential equation of the fourth order:</p>
        <p><inline-graphic xlink:href="images/image21.jpeg" mime-subtype="jpeg"/>       ....(19)</p>
        <p>Integrating the equation (19) twice we find:</p>
        <p><inline-graphic xlink:href="images/image22.jpeg" mime-subtype="jpeg"/>          …(20)</p>
        <p>where C<sub>3</sub> and C<sub>4</sub>  there are constants of integration.</p>
        <p>For the solution of the equation (20) we shall find the general solution of the homogeneous equation. We shall write down the characteristic equation:</p>
        <p><inline-graphic xlink:href="images/image23.jpeg" mime-subtype="jpeg"/>      …..(21)</p>
        <p>Solutions of a quadratic equation (21) look like:</p>
        <p>K<sub>1</sub> = -ln2, K<sub>2</sub> = - ln2/γ     ….(22)</p>
        <p>Hence the general solution of the homogeneous equation looks like:</p>
        <p><inline-graphic xlink:href="images/image24.jpeg" mime-subtype="jpeg"/>…..(23)</p>
        <p>Where C<sub>5</sub>  and C<sub>6</sub>  there are constants of integration.</p>
        <p>The particular solution of the equation (20) we shall search as a polynom:</p>
        <p><inline-graphic xlink:href="images/image25.jpeg" mime-subtype="jpeg"/>   …….(24)</p>
        <p>where<italic> A</italic>,<italic> B</italic> and<italic> D</italic> there are constant factors.</p>
        <p>Substituting (24) in (20) we shall find:</p>
        <p><inline-graphic xlink:href="images/image26.jpeg" mime-subtype="jpeg"/>    .....(25)</p>
        <p>Equating factors at identical degrees<italic> n</italic> we find:</p>
        <p><inline-graphic xlink:href="images/image27.jpeg" mime-subtype="jpeg"/>    ......(26)</p>
        <p>Constant<italic>D</italic> in (24) to find there is no necessity.</p>
        <p>Thus the particular solution (24) of equation (20) looks like:</p>
        <p><inline-graphic xlink:href="images/image28.jpeg" mime-subtype="jpeg"/>              ….(27)</p>
        <p>Hence the solution of the equation (20) will be written down as the sum (23) and (27):</p>
        <p><inline-graphic xlink:href="images/image29.jpeg" mime-subtype="jpeg"/> ......(28)</p>
        <p>Let's accept the initial condition: at n=0 size is q<sub><italic>f1</italic></sub> = q<sub><italic>f0</italic></sub>.</p>
        <p>Hence:</p>
        <p>q<sub><italic>f0</italic></sub> = C<sub>5</sub> + C<sub>6</sub> + D   …….(29)</p>
        <p>Thus:</p>
        <p><inline-graphic xlink:href="images/image30.jpeg" mime-subtype="jpeg"/>      .....(30)</p>
        <p>The found solution (30) characterizes the sum of two processes: duplication of individuals of the first population - first three terms, and the influence on a population - the fourth term.</p>
        <p>Absence of influence on the first population there are probably in two cases. First, at α<sub>1</sub> = 0 , i.e. the second population does not operate on the first population; second, at α<sub>2</sub> = α<sub>1</sub> = 0 these populations develop independently from each other and thirdly, zero value of expression in brackets of the fourth term (30).</p>
        <p>Last case is most interesting. It is connected to a variant when on the first population, for example, human, was influence of the second population, for example, virus,  but then it has stopped since the human population has developed immunity to influence of a virus population.</p>
        <p>Let's equate last bracket (30) to zero:</p>
        <p><inline-graphic xlink:href="images/image31.jpeg" mime-subtype="jpeg"/>          .....(31)</p>
        <p>The equation (31) allows find dimensionless time of immunity development at the first population to influence of the second population:</p>
        <p><inline-graphic xlink:href="images/image32.jpeg" mime-subtype="jpeg"/>            …..(32)</p>
        <p>Dimensional time is equal:</p>
        <p><inline-graphic xlink:href="images/image33.jpeg" mime-subtype="jpeg"/>  .....(33)</p>
        <p>Unfortunately, the formula (33) has a uncertain constant  C<sub>3</sub>.</p>
        <p>The constant C<sub>3</sub>. is defined according to (19) the sum of initial values of first three derivatives on time from the allele frequency q<sub><italic>f</italic></sub><sub><italic>1</italic></sub>. Integrating (19) once at n=0  we shall find:</p>
        <p><inline-graphic xlink:href="images/image34.jpeg" mime-subtype="jpeg"/>        ……..(34)</p>
        <p>Let's assume γ = T<sub>2</sub>/T<sub>1</sub>  very small size. It is possible since average time of a cell life of the person usually is much greater average time of a virus life. In this case according to (34) a constant is C<sub>3</sub> ≈0.</p>
        <p>The formula (30) at  C3 ≈0 also γ&lt;&lt;1  looks like:</p>
        <p><inline-graphic xlink:href="images/image35.jpeg" mime-subtype="jpeg"/>    .....(35)</p>
        <p>At C<sub>3</sub> ≈0   dimensionless time of influence attenuation of the second population on the first population (32) it is equal , n<sub>lmm</sub> =2/ln2 ≈ 2,9 dimensional time (33) is equal t<sub>lmm</sub> =2/ln2 ≈ 2,9T<sub>1</sub>≈400days. Found time of collective immunity occurrence - almost 3 average of time of a cell life of an individual. After the ending of influence of the second population on the first the last term in (35) becomes equal to zero. There is a free duplication in the first population. Taking into account also γ&lt;&lt;1 it is possible to write down:</p>
        <p><inline-graphic xlink:href="images/image36.jpeg" mime-subtype="jpeg"/>    .....(36)</p>
        <p>The law of free duplication of a population looks like <xref ref-type="bibr" rid="ridm1842899164">1</xref><xref ref-type="bibr" rid="ridm1842968316">2</xref>:</p>
        <p><inline-graphic xlink:href="images/image37.jpeg" mime-subtype="jpeg"/>                           …..(37)</p>
        <p>where q<sub><italic>fo</italic></sub> there is initial frequency of examined recessive allele at the woman, q<sub><italic>m</italic></sub><sub><italic>0</italic></sub>  - at the man.</p>
        <p>Comparing (36) and (37) we find C<sub>5</sub> = (q<sub>f0</sub> - q<sub>m0</sub>)/3. As it was supposed, appeared C<sub>6</sub> = 0, since q<sub><italic>f1</italic></sub> at free duplication of individuals should not depend on size γ. Therefore the formula (35) can be copied as:</p>
        <p><inline-graphic xlink:href="images/image38.jpeg" mime-subtype="jpeg"/>  …...  (38)</p>
        <p>On <xref ref-type="fig" rid="idm1842754236">Figure 2</xref> change of an allele frequency q<sub><italic>f</italic></sub><sub><italic>1</italic></sub>  the first (human) population in time at absence of influence (curve 1), and at presence of influence (curve 2) of the second (virus) population is shown.</p>
        <fig id="idm1842754236">
          <label>Figure 2.</label>
          <caption>
            <title> Change of the allele frequency qf1 in time at the first (human) population at absence of influence of the second (virus) population (curve 1) and at presence of influence (curve 2). Parameters for calculation qf0 = 0,3; qmo = 0,3; γ = 0,005; α1 = -0.1; α2 =-0.01.</title>
          </caption>
          <graphic xlink:href="images/image39.jpg" mime-subtype="jpg"/>
        </fig>
        <p>From <xref ref-type="fig" rid="idm1842754236">Figure 2</xref> it is visible that allele frequency at absence of influence of a virus population gradually falls coming nearer to equilibrium value q<sub>f1</sub> = (2q<sub>f0</sub> + q<sub>mo</sub>)/3 = 0,23 . At influence of a virus population the allele frequency on which influence is carried out (curve 2) first falls very quickly due to destruction of cells and accordingly alleles but then in process of development of immunity at n<sub>imm</sub> = 2/ln2 ≈ 2,9  and duplication of cells the frequency grows reaching the normal level corresponding to a curve 1. The further growth of a curve 2 shown by a dotted line apparently of biological sense has no.</p>
      </sec>
    </sec>
    <sec id="idm1842729060" sec-type="conclusions">
      <title>Conclusion</title>
      <p>The used genetic-mathematical model of interaction of the populations based on the Hardy - Weinberg law allows calculate some distinctive features of process of interaction of populations. It can be used at an estimation of duration of pandemic COVID-19.</p>
      <p>It is marked that the virus population actions not with a human population as set of very complex organisms, and with a population of separate cells of the person bodies. As an example cells of a liver are used. It is shown that duration of pandemic process in this case makes approximately 400 day.</p>
      <p>With the help of the equations of a population development it is shown that cells of a human population first intensively perish under influence of viruses but then at development of the immune answer due to duplication of cells the organ of the person is restored up to a normal level. The destruction of an individual (person) at virus attack is exclusive enough event connected to full destruction already beforehand weakened organ for accompanying reasons.</p>
      <p>Dynamics of development of a virus population at its interaction with a human population is shown. Intensity of destruction of viruses in particular a flu as well investigated disease at action of immune system of the person is designed.</p>
    </sec>
  </body>
  <back>
    <ref-list>
      <ref id="ridm1842899164">
        <label>1.</label>
        <mixed-citation xlink:type="simple" publication-type="journal">
          <name>
            <surname>A</surname>
            <given-names>N Volobuev</given-names>
          </name>
          <article-title>Genetic-mathematical modelling of mutational processes in a population</article-title>
          <date>
            <year>2019</year>
          </date>
          <source>Journal of Genetic Engineering</source>
          <volume>1</volume>
          <issue>1</issue>
          <fpage>1</fpage>
          <lpage>9</lpage>
        </mixed-citation>
      </ref>
      <ref id="ridm1842968316">
        <label>2.</label>
        <mixed-citation xlink:type="simple" publication-type="journal">
          <name>
            <surname>A</surname>
            <given-names>N Volobuev</given-names>
          </name>
          <name>
            <surname>I</surname>
            <given-names>L Davydkin</given-names>
          </name>
          <name>
            <surname>A</surname>
            <given-names>V Kolsanov</given-names>
          </name>
          <name>
            <surname>D</surname>
            <given-names>A Kudlai</given-names>
          </name>
          <date>
            <year>2020</year>
          </date>
          <publisher-name>Mathematical Genetics.Samara:ANO Publishing House SSC</publisher-name>
        </mixed-citation>
      </ref>
      <ref id="ridm1842983004">
        <label>3.</label>
        <mixed-citation xlink:type="simple" publication-type="journal">
          <name>
            <surname>Libbert</surname>
            <given-names>E</given-names>
          </name>
          <article-title>Kompendium der allgemeinen biologie.Jena:VEBGustav FisherVerlag</article-title>
          <date>
            <year>1982</year>
          </date>
        </mixed-citation>
      </ref>
      <ref id="ridm1843000172">
        <label>4.</label>
        <mixed-citation xlink:type="simple" publication-type="journal">
          <name>
            <surname>Vogel</surname>
            <given-names>F</given-names>
          </name>
          <name>
            <surname>Motulsky</surname>
            <given-names>A</given-names>
          </name>
          <date>
            <year>1990</year>
          </date>
          <source>Human Genetics.Berlin:Springer-Verlag,Berlin,.Volumes</source>
          <fpage>1</fpage>
          <lpage>3</lpage>
        </mixed-citation>
      </ref>
      <ref id="ridm1842760172">
        <label>5.</label>
        <mixed-citation xlink:type="simple" publication-type="book">
          <name>
            <surname>Li</surname>
            <given-names>C C</given-names>
          </name>
          <date>
            <year>1976</year>
          </date>
          <chapter-title>First Course in Population Genetics.California:TheBoxwoodPressPacificGrove</chapter-title>
        </mixed-citation>
      </ref>
    </ref-list>
  </back>
</article>
