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   <ui>gb-2003-5-1-p2</ui>
   <ji>GBJ</ji>
   <fm>
      <dochead>Deposited research article</dochead>
      <bibl>
         <title>
            <p>Is prokaryotic complexity limited by accelerated growth in
regulatory overhead?</p>
         </title>
         <aug>
            <au id="A1">
               <snm>Croft</snm>
               <mi>J</mi>
               <fnm>Larry</fnm>
               <insr iid="I1"/>
               <insr iid="I4"/>
            </au>
            <au id="A2">
               <snm>Lercher</snm>
               <mi>J</mi>
               <fnm>Martin</fnm>
               <insr iid="I2"/>
            </au>
            <au id="A3">
               <snm>Gagen</snm>
               <mi>J</mi>
               <fnm>Michael</fnm>
               <insr iid="I1"/>
               <insr iid="I3"/>
            </au>
            <au id="A4" ca="yes">
               <snm>Mattick</snm>
               <mi>S</mi>
               <fnm>John</fnm>
               <insr iid="I1"/>
               <email>j.mattick@imb.uq.edu.au</email>
            </au>
         </aug>
         <insg>
            <ins id="I1">
               <p>ARC Special Research Centre for Functional and Applied Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072, Australia</p>
            </ins>
            <ins id="I2">
               <p>Department of Biology and Biochemistry, University of Bath, Bath BA27AY, UK</p>
            </ins>
            <ins id="I3">
               <p>Physics Department, University of Queensland, Brisbane, Qld 4072, Australia</p>
            </ins>
            <ins id="I4">
               <p>Current address: Novartis Institute for Biomedical Research, Basel 4056, Switzerland</p>
            </ins>
         </insg>
         <source>Genome Biology</source>
         <issn>1465-6906</issn>
         <pubdate>2003</pubdate>
         <volume>5</volume>
         <issue>1</issue>
         <fpage>P2</fpage>
         <url>http://genomebiology.com/2003/5/1/P2</url>
         <note>This was the first version of this article to be made available publicly. This article was submitted to <it><b>Genome</b> Biology</it> for peer review. </note>
         <xrefbib>
            <pubid idtype="doi">10.1186/gb-2003-5-1-p2</pubid>
         </xrefbib>
      </bibl>
      <history>
         <rec>
            <date>
               <day>15</day>
               <month>12</month>
               <year>2003</year>
            </date>
         </rec>
         <pub>
            <date>
               <day>15</day>
               <month>12</month>
               <year>2003</year>
            </date>
         </pub>
      </history>
      <cpyrt>
         <year>2003</year>
         <collab>BioMed Central Ltd</collab>
      </cpyrt>
      <shortabs>
         <p>Two models for the growth of regulatory networks are presented. Both predict that the number of transcriptional regulators will scale quadratically with total gene number.</p>
      </shortabs>
      <abs>
         <sec>
            <st>
               <p>Abstract</p>
            </st>
            <sec>
               <st>
                  <p>Background</p>
               </st>
               <p>Increased biological complexity is generally associated with the addition of new genetic information, which must be integrated into the existing regulatory network that
operates within the cell. General arguments on network control, as well as several recent
genomic observations, indicate that regulatory gene number grows disproportionally fast with
increasing genome size.</p>
            </sec>
            <sec>
               <st>
                  <p>Results</p>
               </st>
               <p>We present two models for the growth of regulatory networks. Both predict that the number of transcriptional regulators will scale quadratically with total gene number. This
appears to be in good quantitative agreement with genomic data from 89 fully sequenced
prokaryotes. Moreover, the empirical curve predicts that any new non-regulatory gene will
be accompanied by more than one additional regulator beyond a genome size of about
20,000 genes, within a factor of two of the observed ceiling.</p>
            </sec>
            <sec>
               <st>
                  <p>Conclusions</p>
               </st>
               <p>Our analysis places transcriptional regulatory networks in the class of accelerating networks. We suggest that prokaryotic complexity may have been limited throughout
evolution by regulatory overhead, and conversely that complex eukaryotes must have
bypassed this constraint by novel strategies.</p>
            </sec>
         </sec>
      </abs>
   </fm>
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         <classification type="BMC" subtype="man_spc_id" id="30010010">Genome studies</classification>
         <classification type="BMC" subtype="man_spc_id" id="30010008">Evolution</classification>
      </classifications>
   </meta>
   <bdy>
      <sec>
         <st>
            <p/>
         </st>
      </sec>
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