Open Access

Is prokaryotic complexity limited by accelerated growth inregulatory overhead?

  • Larry J Croft1, 4,
  • Martin J Lercher2,
  • Michael J Gagen1, 3 and
  • John S Mattick1Email author
Genome Biology20035:P2

DOI: 10.1186/gb-2003-5-1-p2

Received: 15 December 2003

Published: 15 December 2003



Increased biological complexity is generally associated with the addition of new genetic information, which must be integrated into the existing regulatory network thatoperates within the cell. General arguments on network control, as well as several recentgenomic observations, indicate that regulatory gene number grows disproportionally fast withincreasing genome size.


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. Thisappears to be in good quantitative agreement with genomic data from 89 fully sequencedprokaryotes. Moreover, the empirical curve predicts that any new non-regulatory gene willbe accompanied by more than one additional regulator beyond a genome size of about20,000 genes, within a factor of two of the observed ceiling.


Our analysis places transcriptional regulatory networks in the class of accelerating networks. We suggest that prokaryotic complexity may have been limited throughoutevolution by regulatory overhead, and conversely that complex eukaryotes must havebypassed this constraint by novel strategies.