4.4 Article

The molecular and mathematical basis of Waddington's epigenetic landscape: A framework for post-Darwinian biology?

期刊

BIOESSAYS
卷 34, 期 2, 页码 149-157

出版社

WILEY
DOI: 10.1002/bies.201100031

关键词

attractor; epigenetics; gene regulatory network; Neo-Darwinism; systems biology

资金

  1. iCore/Alberta Innovates the Future (AITF)
  2. Canadian Institutes of Health Research (CIHR)
  3. Natural Sciences and Engineering Research Council of Canada (NSERC)

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The Neo-Darwinian concept of natural selection is plausible when one assumes a straightforward causation of phenotype by genotype. However, such simple 1:1 mapping must now give place to the modern concepts of gene regulatory networks and gene expression noise. Both can, in the absence of genetic mutations, jointly generate a diversity of inheritable randomly occupied phenotypic states that could also serve as a substrate for natural selection. This form of epigenetic dynamics challenges Neo-Darwinism. It needs to incorporate the non-linear, stochastic dynamics of gene networks. A first step is to consider the mathematical correspondence between gene regulatory networks and Waddington's metaphoric epigenetic landscape, which actually represents the quasi-potential function of global network dynamics. It explains the coexistence of multiple stable phenotypes within one genotype. The landscape's topography with its attractors is shaped by evolution through mutational re-wiring of regulatory interactions offering a link between genetic mutation and sudden, broad evolutionary changes.

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