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Beyond The Genome: A Non-Reductionist Perspective On Development

Jonathan McLatchie

One common theme which often permeates discussions pertaining to embryology and developmental biology — particularly (but not limited to) within ID circles — is the idea that an organism’s DNA sequence may not wholly be responsible for the development of the three-dimensional structure and architecture found within cells, organs and body plans.

As explained here by biologist Jonathan Wells, every cell of a developing organism (with one or two notable exceptions such as T and B lymphocytes) — whether in the prospective head region of an embryo or in the prospective tail region of an embryo — contains exactly the same DNA sequence (a phenomenon known as “genomic equivalence”). Differential gene expression refers to the activation of different genes within an organism’s respective at specified time-cues during embryogenesis. Head cells must turn on different genes from tail cells, and they “know” which genes to turn on because they are receiving information with respect to their spatial location from outside of themselves — and, thus, beyond the remit of the DNA sequence.

Of critical importance to gene expression patterns are DNA-binding transcription factors. These specialised proteins are responsible for the expression or repression of genes by binding specific nucleotide sequences found in their promoters. Subsequent interaction with their cognate sequences results in a cascade of events. This often involves changes in chromatin architecture, which leads to the assembly of an active transcription complex (Cosma et al. 1999). What is important to note is that the types of transcription factors which are present in a cell are not, in and of themselves, sufficient to define its respective spectrum of gene expression.

DNA methylation patterns, in addition to a few other mechanisms, serve as an elegant “epigenetic memory” system to ensure the irreversibility of differential gene expression (Bird, 2002). In fact, the Bird paper notes that:

A ‘transcription factors only’ model would predict that the gene expression pattern of a differentiated nucleus would be completely reversible upon exposure to a new spectrum of factors. Although many aspects of expression can be reprogrammed in this way (Gurdon 1999), some marks of differentiation are evidently so stable that immersion in an alien cytoplasm cannot erase the memory.

Rinn et al. (2006) note that:

Fibroblasts are ubiquitous mesenchymal cells with many vital functions during development, tissue repair, and disease. Fibroblasts from different anatomic sites have distinct and characteristic gene expression patterns, but the principles that govern their molecular specialization are poorly understood. Spatial organization of cellular differentiation may be achieved by unique specification of each cell type; alternatively, organization may arise by cells interpreting their position along a coordinate system.

The authors then attempt to get around the apparent paradox posed by spatial specificity in relation to genomic equivalence by positing that “target sequences” — molecular zipcodes, if you will — of amino acids are responsible for directing proteins to particular locations in the cell. But such “molecular zipcodes” do not create a spatial co-ordinate system; they presuppose it.

Meyer (2004) explains it this way:

Thus, in each new generation, the form and structure of the cell arises as the result of both gene products and preexisting three-dimensional structure and organization. Cellular structures are built from proteins, but proteins find their way to correct locations in part because of preexisting three-dimensional patterns and organization inherent in cellular structures. Preexisting three-dimensional form present in the preceding generation (whether inherent in the cell membrane, the centrosomes, the cytoskeleton or other features of the fertilized egg) contributes to the production of form in the next generation. Neither structural proteins alone, nor the genes that code for them, are sufficient to determine the three-dimensional shape and structure of the entities they form. Gene products provide necessary, but not sufficient conditions, for the development of three-dimensional structure within cells, organs and body plans (Harold 1995:2767).

A couple of months ago, an interesting paper appeared in Nature by Zhang et al. Triggering epithelial development by using a needle, the researchers documented that, in the laboratory nematode worm, Caenorhabditis elegans, nearby cells and their contractile motions are indispensable for proper development. As the authors note in their methods summary:

To apply external forces to embryos, a needle with a 40-mm blunt end was positioned above embryos that had been immobilized on a glass-based culture dish (IWAKI) coated with poly-lysine and placed on a inverted TCS SP2 confocal microscope (Leica). The microscope was then programmed for a time-lapse sequence in xyzt dimension with a 6-mm z distance, at a 1.6-s periodicity to mimic the pulse of muscle contraction.

Intriguingly, in addition to being the anchor point for epithelial cells, a structure known as the “hemidesmosome,” also serves as a “mechanosensor” which responds to the tension induced by near-by epithelial cells by triggering signalling processes which ultimately result in cell-type differentiation.

We are only beginning to mount the foothills with regards to our understanding of the mechanics of embryo development and the various processes which undergird it. There is still much that is not well understood about development and a wealth of information which still needs to be learned. But I think it is becoming increasingly clear that DNA cannot contain both the necessary and sufficient information for the morphogenesis of organismal form. One is naturally led to wonder how such a sophisticated system controlling embryological development could have arisen by virtue of a Darwinian step-wise process which, it must be borne in mind, traditionally involves changes to the DNA sequence. And we have seen the impotence of the neo-Darwinian synthesis at the DNA level, quite apart from the layers of extra information-rich complexity which presides over life’s show. Alas, to many modern Darwinists, any attempt at critique of such scenarios amounts to a “god-of-the-gaps” argument and violates the cherished principle of methodological naturalism. Even though the odds look vanishingly slim, we are told, and even though we cannot at present conceive of a feasible Darwinian-type scenario which could have produced such a system, there nonetheless must be one. Some evolutionary biologists own up to this and confess that they are compelled to embrace Darwinism not principally for scientific reasons, but for methodological ones (e.g. Lewontin, 1997). While such a position might be quite comfortable for some (they don’t ever have to risk their conceptual edifice being proven false), I simply do not have enough faith to take that position.