Rise of the Animal Kingdom and Epigenetic Mechanisms of Evolution - Building the Most Complex Structure on Earth - page 249

According to Carroll's hypothesis, CREs is ultimately responsible for the evolu-
tion and rewiring of GRNs; hence, the evolution of CREs is “the predominant mech-
anism underlying the evolution of form” ( Carroll, 2008 ). The evolution of CREs is
believed to have resulted from four processes:
1. Mutations in existing CREs (i.e., changes in the base sequences, which may create new
binding sites for new TFs, thus enabling recruitment of new genes in GRNs).
2. Remodeling of existing CREs. Changes in the number, affinity, and topology of transcrip-
tion factor binding sites may change expression of proteins.
3. Loss of transcription factor binding sites.
4. Recruitment of transposable elements.
The empirical support for the hypothesis is still inadequate and, generally, still wait-
ing to be confirmed. The evidence on relevant changes in base sequences (i.e., altera-
tions like those that led to changes in the binding function of CREs), is so rare that they
would hardly account for the enormous amount of morphological diversification in the
animal kingdom. At a fundamental methodological level, Carroll ignores that patterns
of expression of TFs are themselves generally controlled ultimately by extracellular
epigenetic signals such as hormones, growth factors, and cytokines, which commonly
are downstream signal cascades that start in the central nervous system (CNS).
Looking at the accidental random changes in the sequences of CREs as the ulti-
mate source of the evolution of animal morphology, the hypothesis sticks to the neo-
Darwinian mechanism of evolution via random changes. It does, however, displace
the focus from changes in genes to changes in their regulatory elements as the main
venue of the evolutionary process. In doing so, the hypothesis is vulnerable to the
same criticism as the basic neoDarwinian hypothesis.
The GRN Hypothesis of Evolution
Central to this hypothesis developed by Eric H. Davidson and Douglas H. Erwin
( Davidson, 2005; Davidson and Erwin, 2006, 2007; Erwin and Davidson, 2009 ) are
the GRNs, groups of functionally linked regulatory, and signaling genes responsible
for production of TFs and receptors.
GRNs are hierarchical structures composed of modular circuits where those at the
apex of the hierarchy, the stable “kernels” of GRNs, control the early development
and formation of the Bauplan. The middle portion is involved in morphogenesis
and is less stable. The inferior portion, which controls differentiation gene batter-
ies' activities, is the most labile portion. Any mutational change in the middle and
peripheral portions may bring about either unfavorable or favorable changes in the
GRN and in the animal development, but changes in the “kernels” are generally dis-
astrous because they affect early development. The lethality of changes in “kernels”
eliminated carriers of changes during early development. The hypothesis assumes
that the calamitous effects of changes in kernels are the reason why kernels are so
stable and why no new Bauplan at the phylum level evolved during the last 400-500
million years. Mutations in the middle portion and the periphery of the GRN may
change the developmental GRN architecture and “[affect] the expression of multiple
genes downstream” ( Erwin and Davidson, 2009 ).