NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-2013.

Cover of Madame Curie Bioscience Database

Madame Curie Bioscience Database [Internet].

Show details

Development of Biological Potential


Should development come after speciation? Yes, of course, in the new model it is natural, one produces the Anlage and develops it to its potential. The word evolution is derived from the latin term evolvere which means to roll out and that describes precisely the process postulated in the Genomic Potential Hypothesis for the post-Cambrian time. With speciation behind us there remain two distinct phases of evolution in the widest sense of the word, the streamlining of the chemistry in the nucleus, which leaves no traces other than species-specific stem cells, and the post-Cambrian ‘unrolling’ of species and variants that produces a spectacular display of phenotypes. Looks like we are on the right track.

About two hundred years ago it was clear that life's history began in the Cambrian and whatever was before, long or short, was a blank called Precambrian. Even in the 1994 a non-religious book appeared the author of which, de facto placed the origin of life into the Cambrian.1 Darwin sensed the need for more time than 500 million years for his evolution model and that conflict led to an argument with Kelvin who was unaware of radioactive decay and its heating effect upon the earth and had, as a consequence, miscalculated the age of the universe to be no more than 500 million years. The naturalists at that time would have missed the 3 billion-year period of evolution anyway because the methods to find fossils of micro-organisms and to determine the age of the rock matrix had not been developed.2 What difference would it make to know about a period during which nothing overtly happened? It provides a credible basis for a scientific hypothesis of evolution!

Although the first cells and the first macro-organisms are separated by an unimaginable stretch of time, without these early events the planet would have been arid today. Archean rocks, however, reveal an astounding assembly of micro-organisms,3 many of them sufficiently familiar to find a place in today's systematic taxonomy. Life flooded the underground scene to begin the longest bio-period known to us. The old model retrofits this stage by calling it a stasis of 3 billion years. True, the fossil record shows 3.5 billion-year-old cyanobacteria, looking like those 800 million years of age as well as contemporary ones, but that does not really mean that nothing happened, it only shows that cyanobacteria did not change.4 This pattern continues throughout all of the evolutionary history; as soon as a species is recognized in the fossil record it will no longer change significantly. Most macro-organisms were not finished until the Cambrian but then they shattered the tranquility with an avalanche of animals strewn over the shallow Cambrian seas around America, Australia, and all the way to what is now the eastern part of China (all in the Pangea5 configuration). Prokaryotes remained prokaryotes and today they constitute perhaps the most abundant and most adaptable form of life. They are reproductively so successful that any development away from prokaryotic life must be considered a significant step backwards in terms of survival capacity. Potential eukaryotes were invisible for us during the first billion years of the Hadean. The potential to produce, either protozoan, plants, or animals is recognized only when it is expressed.

If indeed the potential for all organisms was there at the moment life appeared, what took them so long to get up and running? Energy minimization is a possible answer, but to make sense of it I must appeal to the power of imagination which lets one penetrate the cell and perceive its minuscule dimension as a cavernous space with chemical reactions occurring in the polymer phase at many different places at once. Looking through a nuclear pore of a eukaryote that lived 2.5 billion years ago6 one would see long strands of DNA and RNA turning and forming loops which occasionally break off, only to be reorganized and incorporated into a different section. The field of view changes constantly; bundles of loops, hairpins and loose ends of DNA hopelessly entwined, jerking and twisting from thermal motion until an RNA loop drifts by, interacts with the bundled DNA for a millisecond upon which the knot falls apart, relieved of internal strain. Certain sections of the DNA have served as a template for new strands, but now some of the previously inaccessible loop sections that have been freed by internal catalysis will also duplicate. In this way one could imagine additional potential of a genomic configuration in a particular cell to be recovered for the production of catalytic or structural proteins. The reorganization of the DNA is a sequence-dependent phenomenon which, by the nature of this molecule, will cause loop-outs, self-cutting and back-splicing of cut-outs into another position until an equilibrium is established wherein forth and back reactions occur equally fast and the nucleus, or rather the DNA, will retain a particular configuration for a majority of its lifetime. Reorganization under the direction of energy parsimony provides the major orienting force, but the equilibrium changes as proteins are produced that catalytically expedite the process. Within cells from the same region these reactions will happen with the precision of a democratically run ballet, nearly the same way in every cell sooner or later. A different initial configuration of clones will lead to different final products and so on, for billions of surviving foci.7 By this process, one might imagine that the basis accumulated for the expression of potential species and variations.

Imagine two long stretches of DNA which are alike except for a few positions in the center. It is energetically favorable for configuration A to bend back upon itself, re-anneal its terminal ends to the middle of the molecule, cause a breakage, and then reinsert the broken piece in the middle of the loop. Molecule B cannot do so because the two or three different bases prevent annealing in the same position, but it can form a loop much smaller at the opposite end where it causes a scission and reinsertion.8 When we compare the linear sequence of these hypothetical DNA polymers, the original minor differences have now been increased substantially because of one step of reorganization that was predetermined by the stability of a configuration but could not be anticipated from mere inspection of the DNA pieces. The process, if carried out over eons, would cause molecules that were similar at the start to be significantly different at the end of the 3 billion-year re-organizational period without the need for a single mutation. Again it is important to remember that no goal is being pursued; the rearrangement leads the nucleus to a less energetic conformation. These processes are restricted to the cell, nothing escapes and nothing enters; the genomic material merely reorganizes according to its potential in the direction of the lowest free energy. Pro-eukaryotes did evolve at the same time as prokaryotes but had a different developmental potential, which became obvious when the oxygen levels in the atmosphere increased significantly. In any event, subsequent eons belonged to genomic refinement, i.e., evolution in the spirit of the Genomic Potential Hypothesis.

And what may drive refinement in this world that knows of no encouraging canines or poisons, summarily called evolutionary pressure, to force progress?

The products of efficient reactions will accumulate faster than the products of inefficient ones and therefore the most robust processes will dominate, no urging required. This is how efficient life forms came about at the cellular level, and this is also the reason why three billion years later well-functioning and efficient forms of macroscopic life (Trilobites lived more than 50 million years) appeared suddenly,9,10 peppering the Cambrian landscape.

The selection is based upon favorable reactions; transcripts may re-enforce their own messages and thus establish a hierarchy that forces development into a particular direction so that the low energy-state now includes the new proteinaceous catalyst. This process took 3 billion years, which is understandable considering the complexity of a nucleus.

Chemistry is a very fast process and one might wonder why the re-arrangement should have taken all of 3 billion years. Analogies provide no answers but they reinforce one's imagination, and in this case “Rubric's Cube” might help to explain why genomic streamlining took so long. Starting with a cube in its most disordered state one begins to twist and turn until the most ordered state has been reached (all red surfaces out, for example). The energy we spend depends upon the length of time it takes to reach that defined end point. So it is for chemical or physical processes which will always tend toward low energy positions, provided that a kinetic path exists between the two states. But the path can be full of minor energy minima, and the process could therefore get stuck in intermediate positions for very long times. The cube was designed to have a path from state A to B, which the initiated will complete in a few minutes. But for the uninitiated the path may be extremely long or never-ending because of many wrong moves that have to be corrected by backing off and starting over again.

Symmetry in biology is one of the many unresolved problems, but complex examples can be observed in the inanimate world. As dust specs are drifting through the wintry sky, water molecules freeze to the surface to form a delicate crystalline marvel of precisely sixfold symmetry.11 Deterministic? No doubt! The architecture of each of the six identical leaflets in one flake is determined in part by the nucleating surface and by the temperature gradients through which it tumbles. While it is said that no two snowflakes are alike, the sixfold symmetry is invariant.

The assembly of animals contains an element of lateral symmetry as well as longitudinal orientation which may be represented by a string of letters that designate complexity factors and subscripts that are symmetry factors whereby 2 means bilateral - and 3,4,5 --n multi-dimensional symmetry. Thus, a bacterium is A1, a starfish A(5–9), and a bony fish might be A2 B2C2D2 + SCF, (Segment Control Factor).

The reader may blend in the scenario of nuclear reactions and be reminded that this is where biological symmetry originates. Let us assign completely imaginary complexity labels, A, B, C, D, E -------------N, to a potential organism. Level A1 is the starting position most frequently attained and that would be typical in microorganisms which has no fixed major axes of symmetry. One could assume that symmetry factors terminate the complexity chain growth and that, if an A could associate with a B before a symmetry factor would prevent lengthening of the string of letters, then a more complex organism could result. Thus A, B, and C would have to find symmetry factors which would take more time than for A and B alone and so on. The original genomic organizational level might be A2 B2 C2 F2 G2 H I J K2 L M N O P Q R2 S, which would be the foundation for a complex ‘bilateral’, provided that the second unit is found for those letters that do not have a subscript. In contrast A2 B C2 is the basis for a simple organism. Required for phenotypical expression is an unbroken series of complexity and symmetry factors and, clearly, it would have taken more time to complete the long series than the small one; such a model would cause simple organisms to appear first and complex ones last. Note that this proposal matches observations and explains in concept why the human fossil record is about 160 million years shorter than that of a frog. It may be a simple model but it addresses a functional aspect of organogenesis and is therefore quite advanced compared to the standard model that advocates searching for Lucy's (A. afarensis) grandmother in a litter of tree shrews.

Energy minimization of the genetic material in the nucleus can be displayed as an asymptotic curve that edges ever closer to a minimum. Upon close scrutiny innumerable small energy valleys may be seen superimposed on the general trend wherein a conformation could get stuck for a long time. This roughness is related to the tremendous size of a genome. If a favorable conformation occurs on one end and another one at the other end, upon coming together those two folds may turn out to be unfavorable for the overall energy. Hence the large nucleic acid molecule can go through many conformational and covalent bond changes that, just like turning sections of Rubric's Cube, would have nearly equal energy differences, and a wrong move at one point might similarly require a return to another starting configuration before successful reorganization can occur. For eukaryotes the final state must be so efficient that the 3 billion base pairs of the genome can be unrolled, duplicated, and reorganized in the few minutes of a mitotic cycle. For that feat basic proteins had to be recruited about which nucleic acid could be wound and unwound in the few minutes of a duplication cycle.

Complexity increases if one factors-in the effects of the gene products, namely the proteins that form cellular structures or biological catalysts. Some of these proteins do regulate the expression of genomic material and in the process combine with DNA to either inhibit or promote the translation of the DNA into proteins. Thus, the gene products enter this equilibrium toward conformational and structural stability and the speed with which these reactions occur may cause the genome to stay on one of the conditional energy recesses where it is more responsive to control than it would be in an absolute minimum state. There is no evidence for this suggestion and our level of experimental sophistication is not sufficient to produce any. In principle, this problem can be addressed because it is embodied in a structure.

Arrival at this metastable state wherein the existence of a genomic configuration depends on the continuous rapid production of proteins was the signal, the moment when macro-organisms might have arisen from cells. The simplest nuclei reached that equilibrium first and the most complex ones did so later, and therefore the time of appearance of species in the fossil record is inversely related to complexity . Species persist as long as the genomic material is maintained in that metastable state and slight shifting across the bottom of this conditional energy valley may cause members of a species to grow larger, smaller, to develop or lose appendages. But essentially they will stay what they are for their whole existence on earth, which varies from about 5 to 500 million years for animals to 3.5 billion years for microorganisms. One may speculate that this metastable state is essential for the persistence of a species and that, when after millions of years the genomic material drops into an absolute energy valley, extinction will ensue regardless of catastrophes!

Thus, the genome goes from the incipient state to childhood, adult life, senescence, and death, and as it does it expresses itself in different forms. Childhood would be the time when the genetic mechanisms develop, and adulthood would result in an escape from the single cellular state to the production of animals and plants. Genomic senescence (the absolute energy valley) may be an inescapable phenomenon that will eventually lead to the extinction of species.

To be effective the genomic configuration must have a consequence in terms of proteins that provide structural stability or catalytic activity. Beyond the well-known concept of the dependence of protein structures upon linear genomic coding sequences there may well be a relationship that makes proteins produced within one cell compatible with each other. This difficult concept requires some reflection upon the function of structural features of macromolecular surfaces. The argument is based upon the suggestion that interacting coding sequences might give rise to interacting proteins (the most simple example). This prediction is an educated speculation and the evidence that can be cited in support is very scarce. Attempts have been made to find such a relationship between receptor/ligand pairs.12,13 The new methodology, called proteomics, may promote discovery of relations that may be relevant for this proposal.14 It is not impossible that the initial DNA structure induced organization and thus loaded the dice for the nuclear refinement process a little different in each case.

So much for a period that is generally ignored as the most uneventful phase of evolution. Of course, most of what has been said about the interregnum is speculation, induced by the genomic potential hypothesis of evolution. True, the skeleton of facts concerning this period has been fleshed out which is the normal function of a hypothesis. Evidence for the existence of bacterial life 3.5 billion years ago is, however, unequivocal3 as is the fact that larger cells were found 2.2 billion years ago15 (the time appears to be pushed back with every new report). The appearance of macro-organisms in unimaginable numbers and variety during the early Cambrian period is also well documented in the fossil record and that leaves one no choice but to view the development of macro-organisms as the display of the configuration that the genomes had perfected during the eon of single cellularity; it was the egg that evolved.

There it is, the story of the main events in evolution, shrouded in nebula as is the black hole at the center of our galaxy. We can know it is there by the way it pulls in stars and gases as it bends space into a whirlpool of gravity, and we know that the evolutionary events were there by the way they spew finished creatures from an invisible past without much warning and with their origin hidden from our view.


Senapathy P. Independent Birth of OrganismsGenome Press, Madison1994.
Lopuchin AS. Structures of biogenic origin from early Precambrian rocks of Euro-Asia. Origins of Life. 1975;6:45. [PubMed: 807898]
Schopf W. Microfossils of the early Archean Apex chert: New evidence of the antiquity of life. Science. 1993;260:640. [PubMed: 11539831]
Pennisi E. Static evolution. Science News. 1994;145:168.
Stanley SM. Earth and Life Through TimeViking Press, New York1986.
Brocks JJ, Logan Ga, Buick R. et al. Archean molecular fossils and the early rise of eukaryotes. Science. 1999:1033. [PubMed: 10446042]
Schwabe C, Warr GW. A polphyletic view of evolution: the genetic potential hypothesis. Perspectives in Biology and Medicine. 1984;27:465. [PubMed: 6374609]
Celander DW, Cech TR. Visualizing the higher order folding of a catalytic RNA molecule. Science. 1991;251:401. [PubMed: 1989074]
Cisne JL. Trilobites and the origin of arthropods. Science. 1974;186:13. [PubMed: 17818086]
Gould SJ. Wonderful LifeW. W. Norton, New York1989.
LaChapelle E. Field Guide to Snow CrystalsUniversity of Washington, Press, Seattle1969.
Goldstein A, Brutlag DL. Is there a relationship between DNA sequences encoding peptide ligands and their receptors? Proc Natl Acad Sci USA. 1989;86:42. [PMC free article: PMC286399] [PubMed: 2536158]
Fassina G, Zamai M, Brigham-Burke M. et al. Recognition properties of antisense peptide to Arg-8-vasopressin/bovine neurophysin II biosynthetic precursor sequences. Biochemistry. 1989;28:8811. [PubMed: 2605222]
Borman S. Proteomics: Taking over where genomics leaves offC&EN2000.
Knoll AH. A new molecular window on early life. Science. 1999;285:1025. [PubMed: 10475845]
Copyright © 2000-2013, Landes Bioscience.
Bookshelf ID: NBK6472


  • PubReader
  • Print View
  • Cite this Page

Related information

  • PMC
    PubMed Central citations
  • PubMed
    Links to PubMed

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...