THE BLOG
12/08/2015 12:36 pm ET Updated Dec 05, 2016

Are We Toys?

It's not easy to make a new kind of organism. The rewiring and reconfiguration of embryonic development and physiological function as a consequence of long periods of evolution, referred to as "developmental system drift," makes it unlikely that we can discern the kinds of "genotype to phenotype" maps necessary to rationally redesign the features of present-day organisms (a dream of genetic engineering and the new field of synthetic biology), without incurring unexpected outcomes. This conclusion has been confirmed in many experiments.

The basis of this degradation of genetic determinism is clear. Ever since animals and plants first appeared in the biosphere (estimated at more than 600 million years ago for the former, and 500 million years ago for the latter), there has been an enormous amount of additional genetic change, sometimes associated with the evolution of new biological features, but frequently reinforcing existing ones. These mostly random changes could occur along different "pathways" in genealogically related lines of descent, meaning that shared body forms and common anatomical structures often develop by utilizing different genetic circuitry. The segmented backbones of a zebrafish and a mouse, for example, are produced using gene sets that are only partly overlapping, and the gene overlap is even less for the generation of identical-looking digestive systems and reproductive organs in different species (even within the same genus) of nematode worms.

When we focus instead on the more pristine multicellular systems that gave rise to the first animals, however, a very different and rather unnerving picture emerges of how a few specific gene modifications led to dramatic and surprisingly comprehensible changes in the resulting biology. We know about the ancient history of the animals not only from the fossil record, but by way of the same DNA sequencing and "informatics" (i.e., computational) techniques that have permitted us to make the genetic comparisons between related present-day species described above. The animals arose within an ancient population of unicellular organisms, the "choanoflagellates," of which there are still living members we can study. These cells could attach loosely to one another, but they did not form multicellular animals until two things happened. First, some proteins on the cells' surfaces that occasionally mediated cell-cell attachment (cadherins) gained an entirely new domain that reached through the cells' membranes into their "cytoskeletons," the network of fibers that moves their internal contents around. Second, a new protein appeared, Wnt, which diffused between cells and indirectly (through its influence on the cytoskeleton) affected the strength and surface distribution of cell-cell attachment sites.

These novel features (which remain active in all animal embryos to this day) permitted cells to rearrange within cohesive clusters, while enabling masses of cells with nonuniform surfaces to acquire interior spaces, the first body cavities. They defined the simplest animals - sponges: cell masses with labyrinthine channels, and placozoans: purse-like sacks composed of two layers of cells separated by a gel-filled space - and coincided with their origination.

The next major event in animal evolution was the emergence of the "diplobasts," animals with distinct tissue layers - only two to begin with. These included jellyfish, hydra and corals in one main group ("phylum"), and comb jellies in the other. Similarly to the origination of the animals themselves, the arrival of this new group was accompanied by a small number of novel proteins (specified by previously nonexistent genes) that performed unique and straightforward form-producing ("morphogenetic") functions. One of these proteins was peroxidasin, an enzyme that cross-linked collagen molecules which formed part of the soft cell surrounding materials in earlier-appearing animals, generating instead the flexible sheet-like stabilizing barrier between tissue layers known as the "basal lamina." Others were a small set of intracellular relay proteins (Vang/Stbm is an example) that cause cells to reorganize their cytoskeletons and change shape in a concerted fashion, in response to the same Wnt signal whose appearance, as mentioned above, coincided with that of the animals. This entirely new response to Wnt enabled tissues as a whole to narrow and elongate, leading to extended bodies and appendages.

Also accompanying the arrival of the diploblasts were other previously nonexistent proteins, the innexins, which form grommet-like pores at the interfaces of adjacent cells. These "gap junctions" permit ions and other small molecules to pass from cell to cell, enabling a global integration of tissue function not possible by Wnt alone, which has only a limited spatial range of activity. Organisms with these features: distinct tissues, extended bodies and appendages, and wide-ranging integration of function, while they were not the very first animals, are the earliest-appearing ones in which we can begin to recognize our biological selves. They are termed "eumetazoans" (true animals).

The next major innovation of animal bodies, which occurred leading up to, and during, the Cambrian Explosion, led to the emergence of the triploblasts, animals with three main tissue layers. Triploblasts take many different forms, including mollusks (e.g., clams and octopuses), arthropods (e.g., flies and lobsters), and chordates (e.g., sea squirts and humans). They are the only animals with internal organs, the most successful types ecologically, and constitute the majority of animal phyla. Many triploblast groups are associated with an entirely new collection of previously nonexistent proteins, mediating previously unprecedented functions. The functions in the case of the triploblasts often involve "extracellular matrix" (ECM) molecules that promote the tissue disaggregation and invasion necessary to produce the third layer. These are partly shared among different triploblast phyla, but in some cases they are entirely specific to a single group. In chordates, for example, fibronectin and hyaloronan, a protein and a polysaccharide, two ECM molecules absolutely essential to the development and integrity of the chordate body, are exclusive to this phylum (as is the unique enzyme, functioning unlike anything else in the animal kingdom, which synthesizes hyaluronan). Chordates even have their own specific gap junction proteins, connexins, that are unrelated to the innexins or proteins of any other organism.

This is not how evolution is supposed to have occurred according to the standard, neo-Darwinian scenario. Evolution by natural selection proceeds in gradual steps, with every potentially favorable genetic change having just a small effect, increasing its representation in a population until, after many such cycles, there is a large-scale change in the overall phenotype. The cases I have described, which are in fact the most important events in the history of the animals, occurred through genes of large effect, and unprecedented genes at that. Although it is always possible to contrive gradualist scenarios, with postulated extinctions of all intermediate forms and proteins, there is no evidence at all that things happened in that fashion. Furthermore, the successively more complex and sophisticated animal populations failed to supplant their progenitors, an expectation of evolution by competition. The biosphere continues to harbor unicellular choanoflagellates, "basal" animals like sponges and placozoans, and diploblasts like jellyfish and corals.

The impression given is much more of a progressive addition to available life-forms (by whom or what being a matter of pure speculation) of new gadgets and contraptions suited to specific morphogenetic tasks: first to free-living cells, turning aggregates of them into primitive animals; then to some of these autonomous multicellular forms, converting them to elongated animal bodies with separate tissues and appendages; finally to these relatively simple animals, transforming a subset of them into highly complex, organ-bearing creatures.

While not favorable to Darwin's model, this "Development App" scenario is even less congenial to the Creationists' godly alternative. A foresightful and all-powerful deity would presumably have cut to the chase and made the animals, and our exalted selves, all at once, rather than embellishing existing formats with clever, though not particularly profound gimmicks. Perhaps during this holiday season, as we await the delivery of the games and devices that increasingly enhance or substitute for life's meaning, we might turn our thoughts to the presumed developers and gamesters of the distant past who worked tirelessly to make us what we are.