Richard Hoppe points out that one of the articles I cited in my discussion of Vernanimalcula has some interesting implications, so I thought I'd expand a bit on some points brought up in a couple of these Davidson papers.

One idea is a general one that we have to keep in mind when studying the evolution of developmentally significant molecules—genes don't necessarily have the simple functions that we assign to them. For example, one of the better known genes in the popular press is BRCA1, named because certain alleles of this gene are associated with a higher frequency of breast cancer. It is not a breast cancer gene, of course; the gene product is a nuclear phosphoprotein with a bewilderingly complex set of functions. We have to be careful not to think that the convenient handle we attach to genes when we name them by the initial description of a phenotype when they are defective is an at all accurate or complete description of their normal function.

Erwin and Davidson discuss some of these misleading conceptual associations we fall prey to in development. Here is a table of a few examples of genes that have a proposed, simple function, and a better alternative function:

Diverse interpretations of some examples of gene use across Bilateria

For example, you will often hear pax6 described as a 'master control gene for eye formation'; I've done that myself. It's a gene that is expressed in a pair of fields at the anterior end of the animal, where the eyes will form, and misexpressing it in other regions of the animal will induce eyes to form in ectopic locations, so it is easy to slip into the habit of thinking of it as the gene that makes an eye. It isn't. It would be better to consider it a component of a regulatory network of genes, characterized by an upstream pattern of regulation that induces its expression in a specifically localized anterior field, which in turn induces a pattern of downstream gene activity that will initiate development of a photoreceptor.

"It's a gene that makes an eye" is a heck of a lot easier to say.

The evolutionary significance of the more complex understanding of its role, though, is that the diverse eyes of multicellular animals may have evolved independently, but all use pax6 because it was part of a conserved module for activating genes needed for an eye.

In development, morphogenetic regulatory programs for pattern formation precede the institution of cell differentiation programs, but it is likely to have been the reverse in the evolution of body parts. This would allow for the continuing selective advantage, at each evolutionary stage, afforded by the respective differentiated cell functions. As an example, consider the famous case of pax6, a transcriptional regulator utilized in the morphogenesis of eyes in both insects and vertebrates. The common view is that this morphogenetic function of pax6 is a pleisiomorphy descendant from the common PDA. The alternative is that what is actually homologous in the role of the pax6 gene in the diversely constructed eyes of various bilaterians is only its function in the control of genes encoding visual pigments. All eyes of all kinds require visual pigment genes, and this is the pleisiomorphic role of pax6; the gene was later coopted for use in the different morphogenetic programs that produce the different structures on which the pigment cells are mounted in different creatures.

A related idea from Peterson and Davidson (2000) is that what was going on in pre-Cambrian metazoan evolution was the assembly of a sophisticated and flexible toolbox of genes that had specific functions in bilaterian ancestors, but could be readily redeployed for novel functions by regulatory changes—that is, the tools were all present and functional, and are still present as common elements in all metazoans, but what has changed is how they get used in development. Here is a pretty figure (click on it for a larger version) they used to illustrate a little bit of the history of major evolutionary inventions; one of their points is that all of these were in place before the Cambrian.

A cladogramof basal metazoans and some of the important regulatory inventions leading to the crown group bilaterians (purple triangle). The dotted line leading to Ctenophora reflects the equivocal nature of evidence regarding their phylogenetic position. The change in grade of organization from a two-dimensional to a three-dimensional form required the evolution of endomesoderm. This stage is indicated by the light-blue line. With the evolution of set-aside cells and regional specification mechanisms, macroscopic bilaterian body plans are now evolvable, and this change is indicated by the purple line. By the time the crown group evolved, all signaling pathways and transcription factor (TXF) families had appeared. The single ‘‘primordial’’ Hox gene found in sponges is shown by the black box. Presumably this gene underwent tandem gene duplication resulting in two genes, an ‘‘anterior’’ gene related to Hox 1 and Hox 2 of bilaterians (shown in red) and a posterior gene related to Hox 9–13 (i.e., Abd-B relatives, shown in blue). A central class Hox gene has been found in ctenophores (Hox 4–8, shown in green). The latest common ancestor must have had at least seven Hox genes involving both gene duplications of previous classes (e.g., multiple anterior and middle genes) and new classes (Hox 3, violet box). This view of Hox cluster evolution devolves from studies of de Rosa et al., Finnerty and Martindale, and others.

The point is that the genes we've studied to infer common descent are truly ancient, 600 million years old or more. What makes a jellyfish different from a human being isn't that we have Hox genes and they don't (because, as you can see, they do), but that evolution has elaborated on the control circuitry behind them.

By the time the crown group of Bilateria appeared, all signaling pathways and transcription factor families were present, because they are common to all modern bilaterians. The important conclusion follows that evolution of phylum-specific body plans does not depend on invention of new developmental genes but rather on novel gene regulatory circuitry. The advent of this circuitry, that is, of regional specification mechanisms including the Hox gene complex, occurred by the latest Precambrian if not before. In our view, it is likely that this was preceded by a long prior history of bilaterian micrometazoans similar in grade of organization to the primary larvae of modern bilaterians.

What they propose to have been different about those archaic bilaterian metazoans is that they relied more on lineage-dependent developmental processes; that is, that cells are immediately specified for a particular fate upon cleavage or before. This is the kind of pattern of development that generates larval forms in modern echinoderms and lophophorates and molluscs and others...all those animals that have a reasonably invariant embryogenesis to produce a characteristic larva. It's those late features in the diagram above, set-aside cells and regional specification mechanisms, that have increased the versatility of metazoan development. What they suggest is that the 'special' attribute of more complex animals is that they can set aside populations of relatively indeterminate cells in early embryogenesis that can later make decisions on the basis of positional information about how to differentiate.

Erwin DH, Davidson EH (2002) The last common bilaterian ancestor . Development 129:3021-3032.

Peterson KJ, Davidson EH (2000) Regulatory evolution and the origin of the bilaterians. PNAS 97(9):4430-4433.