The evolutionary exaptation of the endocrine and immune systems from neural ectoderm homeobox genes. A main objective of genetical research is to elucidate ...
Acta Biotheoretica 41: 267-269, 1993. 9 t993 KluwerAcademic Publishers. Printed in the Netherlands.
IDEAS IN THEORETICAL BIOLOGY
AUTOLOGOUS CLONES The evolutionary exaptation of the endocrine and immune systems from neural ectoderm homeobox genes.
A main objective of genetical research is to elucidate genomic architecture and evolution. Great advances have been made since the relatively recent identification of deoxyribonucleic acid as the primary reproductive material. The entire nucleotide sequences of first several viruses and mitochondria were described and then those of higher organisms. Now sequencing of the human genome proceeds apace. Thus it is becoming possible to appreciate general themes in genomic form and function as arrangements become refined through darwinian evolution. One general theme of note is the parsimony by which novel uses are made of extant forms or functions. These have been termed "exaptations" with respect to unexpectedly propitious adaptative value (Gould, 79). Exaptations are those existing traits which inadvertently become highly adapted to new selective pressures. Generally, exaptations are terminal modifications of recent evolutionary forms or functions rather than alterations of deeply canalized evolutionary traits. But exaptational parsimony also exists at the deeper levels of genomic structure and evolution and, moreover, it sometimes arises in a manner that is not merely propitious, as with the phenomenon of autologous clones. Autologous clones are diploid genes which occur in an individual. Such copies are considered mutant duplications when deleterious, but when salubrious can be termed autologous clones. Most such diploidy is deleterious. However, some is not. Such diploidy can be especially salubrious when the secondary gene can be put to other evolutionary use as an exaptational template while the primary gene remains active. Thus, autologous clones are highly parsimonious exaptations. Of course, most evolutionary themes (such as parsimony) are best appreciated among simpler organisms, e.g., the prokaryote e. coli a genome that has been studied in great detail. On close examination, this genome is noteworthy for elegance and economy of design. There is great parsimony. So too, the genomes of some phages are also ingeniously devised -- so compact as to recall the technology by which semiconductors have been miniaturized. Indeed, small phages are so stressed for ergonomy and spatial efficiency that they evidence remarkable parsimony: they have evolved the use of more than one effective gene from single nucleotide sequences. Among these simple organisms, a successful gene may be duplicated altogether with the copy slightly modified for different but parallel use in exaptational evolution. Similar phenomena have been reported in higher order genomes, as well. Such copies may well have been random mutations. Although there may be a yet undisclosed means by which certain opportunistic mutabilities could be exploited or even
268 stimulated, recourse to such neo-lamarckian and non-darwinian phenomena is not necessary for the present discussion. In any case, across all higher taxonomic levels gene loci are not merely clustered together in functional units, but are sometimes physically the same. The same reproductive material can operate as more than one discrete gene via different processing operations. As it happens, such phenotypic variations derived from a single gene locus may constitute a major mechanism of evolutionary change. Evolution is, after all, highly pragmatic: useful characters are retained. A redundant working gene is more likely to be useful template for evolutionary exaptation (especially with minor refinement) than is a wholly random mutation. A working gene can serve as a template for other evolutionary developments without loss of primary function when it is either duplicated structurally or functionally. Autologous cloning is perhaps the principle means by which templates are devised for subsequent evolutionary refinement via exaptation and related phenomena. This is likely a major source of advancement and efficiency in evolutionary processes. With this in mind, the homeobox system of supragenetical control of genomic development is all the more curious as an example of fundamental parsimony and exaptation. The homeobox genetically specifies (in all but the most proximal and idiosyncratic aspects) the phenotypic development of all multicellular organisms. As such, the homeobox is among the most deeply entrenched features of genome structure and evolution -- a stable feature of the most simple muticellulates to the most complex social insects and mammals (Wimsall, 89). It is the basic plan by which all higher zygotes are oriented for subsequent linear development. It is something of a 'Rosetta Stone' or 'blueprint' whereby phenotypes are constructed. Whole evolved schemae appear to have derived from a single homeobox innovation. This is a most compelling example of the extraordinary biochemical economy and elegant parsimony by which darwinism can sometimes work. Indeed, it has recently been reported that the homeobox system split into three types very early in metazoic evolution (Schubert, 93). Thus, there are traces of this metazoic homeobox innovation evident in every complex organism studied: the antennapedia of the drosophila has essentially the same homeobox as the branchial arches of the human embryo. In passing, one notes phylogeny is ontogenically recapitulated, in Haeckelean fashion. More to the point, the branching of homeobox evolution is worthy of detailed study as an important aid to taxonomy and phylogenetic analysis. The question then arises as to whether further autologous clones have been put to evolutionary use since the metazoic. Also, the question arises as to whether such autologous clones are evident in the human genome. A preliminary answer to each of these questions is yes. By way of clarification, one need look only so far as the parallelism evident in neural, endocrine and immunological biology. Recently, it has become evident that there are striking genetical similarities between the neural, endocrine and immunological systems in vetebrates, mammals and, by implication at least, man. It has been assumed that these parallels are examples of darwinian homologous evolution -- similar traits evolved independent of a direct common ancestral origin. The neural system appears to be phylogenetically the oldest with the other two following on. Indeed, a large number of peptides have been identified in the brain. Of these, most were first familiar from peripheral functions ~utside the central nervous system (Hyman; Nestler, 93). Classic examples are the many peptides first found in the intestinal tract which
269 were later found in the brain. In the gut these control digestive processes whereas in the brain they operate as neurotransmitters. Further examples are also to be noted in how numerous peptides are derived from a common precursor, e.g., pro-opiomelanocortin begets adrenocorticotrophic hormone (ACTH), alpha-melanocyte-stimulating hormone (a-MSH) as well as B-endorphin. So too, the enkephalins are opioid peptides derived from distinct precursor proenkephalin but structurally related to the endorphins. More recently, the sig~na receptor system has been noted to cross-regulate neural, endocrine and immune function. Such cross-linkage points to a common phylogenetic descent of these systems from common ancestral tissue. Embryological studies also point to such evolutionary unity insofar as these systems are, in part, derived from primitive ectodermal genes. Thus, peptide function and structure demonstrates fascinating parsimony in evolution. In darwinian terms, the endocrine and immune systems can be said to have arisen from a common neural primordial ancestor. Likewise, specific molecular constituents of these systems appear to be phylogenetically related, not merely evolved homologues. It is plausible that certain neural genes, successful for their primary purposes, were copied. Once a copy arose, even if only evolutionarily neutral, then subsequent adaptive refinements might be quickly evinced. Thus, the early neural genes may have been duplicated, via autologous cloning, with the copies serving as the founding stock of a new line of evolutionary innovations. These new lines of evolutionary innovation led to endocrinological and immunological systems with genes, processes and other characteristics reminist'ent of the neural system from which they sprang as parsimonious exaptations. Autologous cloning of neural ectodermic homebox genes is a mechanism which can account for the numerous structural and functional similarities in neural, endocrine and immune biology. In fact, from a darwinian vantage it is difficult to avoid the deduction that these systems have arisen by common descent. But it is this very lack of a phylogenetic and evolutionary perspective that has deprived the corpus of neuroscience research a coherence view by which to integration its explosion of data. As Dobzhansky said, nothing in biology makes sense except in light of evolution. This is as true of neuro-endo- immunology as it is of pea pods.
REFERENCES Gould, SJ. and R.C. Lewontin (1979). The spandrels of San Marco and the panglossian paradigm. Proe. R.S.(Lon.) B205: 581-98. Hyman, S. and E. Nestler (1993). The molecular foundations of psychiatry. Washington, APA Press. Schubert, F.R. (1993). Anteanapedia-type homcoboxsplit into three classes early in the metazoic. Proc. Nat. Ae. Sei. (USA) 90: 143-147. Wimsatt, W. (1989). Evolutionary entrenchment. Ethology and Sociobiol. 10: 5.
Daniel R. Wilson Cambridge University Harvard Medical School 19 Clarkson Road Cambridge C B 3 0 E H England
