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EVOLUTION  OF  METAZOANS  AND  THEIR  CONTROL  SYSTEM

 

Evolution of the neuron and the nervous system, determined the unprecedented rapid rates of the evolution of metazoans.

 

 Judging by the incomparably longer period of time it took to occur, evolution of multicellularity has been the most difficult of all the great transitions in the history of life on earth. The main problem to be resolved in the evolution of metazoans was the source of the huge volume of epigenetic information for the spatial arrangement of the myriad of cells in molding animal morphology and the coordination of their activities. Evolution of the first metazoans (the Urmetazoa) and Parazoa (sponges and placozoa), despite the enormous increase of the genetic information, ultimately led to an evolutionary dead end. Only with the evolution of eumetazoans, during the Cambrian explosion, ca. 545 Mya, did the animal kingdom enter the stage of an unprecedented rapid evolution, part of which is the extant fauna with its astonishing diversity of forms and functions. Based on some preexisting forms of epigenetic information that are operational in protozoans, but not in protophyta, eumetazoans succeeded in differentiating the neuron and the ensuing neural net. This was the key event determining the evolutionary success of metazoans. The neural net, whose centralization in the process of evolution led to evolution of the central nervous system, became the source of epigenetic information for erecting the huge multicellular metazoan structure. Being capable of generating that information, the nervous system and endocrine structures under its control became the core of the integrated control system, which took control of animal reproduction, including reproductive behavior, gametogenesis, early development, postphylotypic development, and life history as well as the maintenance of homeostasis and structural identity of the metazoan organism during its lifetime.

 

Principles of Organization of the Multicellular Structure

It might be argued that if laws, rules, and genetic information of unicellulars would have been sufficient for the evolution of multicellularity, evolution of metazoan life would not have taken more than 2 billion years, which is longer than any other event in the evolution of life on earth. Evolution of multicellularity required emergence of new rules and principles of organization of cells in supracellular structures. Unicellulars, by definition, did not need such new rules and principles. For the evolution of multicellular  systems they were indispensable. Some of these principles are self-evident. So, e.g. the development and functioning of multicellular organisms requires differentiation of phenotypically well-defined cell types from cells that are genotypically identical. These cells have to be spatially arranged in strictly determined patterns from which various parts and organs of the multicellular organism arise. Obviously, unicellulars did not need to evolve this capability.

Focusing on metazoans, obviously erection of metazoan structures requires huge amount of information for specifying the spatial arrangement of the myriad of cells they consist of. There is reason to believe that no evolutionary pressure would arise for producing that kind of information in unicellulars.

The metazoan organism has to coordinate the activity of all of its cells and, based on this, perform the higher functions at the organismic level. Obviously this requirement does not apply to unicellulars, hence no evolutionary pressure would arise for evolving mechanisms of coordination of functions of cells in unicellulars.

Cell differentiation, generation of information for the multicellular structure (as well as modes of its transmission to the offspring), and the coordination of the function of all the cells for generating functions at the organismic level, are among the fundamental new attributes that enabled evolution of metazoan life from unicellular organisms.

The complexity arising from aggregation of cells in multicellular structures and coordination of their function unavoidably led to evolution of hierarchies of organization in metazoans. The structural complexity and hierarchical organization, naturally lead to functional compexity (Valentine, 2003) to differentiation and specialization of cells based on the division of labor between them.

The acquisition of the ability to generate information for determining the spatial order of cells in the system facilitated evolution in them of a new type of control system, which is essential for any aggregation of cells that has to rise to the level of a multicellular organism. As argued in chapter 1, no metazoan organism would be able to maintain its structure in absence of a control system. The evolution of such a system that would make the transformation of a colony of unicellulars into a primitive metazoan and later into an eumetazoan organism possible took almost 3 billion years, with the development of the neuron and the nervous net, less than 600 million years ago.

Evolution of unicellular life is obviously depends on the increase in the number and changes in the structure of their genes: mycoplasmas, a group of simplest unicellular organisms known so far, contain in their genome several hundred genes, whereas the prokaryote Escherichia coli, contains more than 4000 genes. A more complex unicellular eukaryote, the protozoan Plasmodium falciparum, has 5300 genes but that number dramatically increased to 40,000 in an evolutionarily higher unicellular eukaryote, Paramecium tetraurelia (Aury et al., 2006). The parallel increase in the number of genes and the degree of functional and structural complexity in the kingdom of unicellular organisms suggests the existence of a causal relationship between genes on the one hand, and the function and morphology in evolution of unicellulars.

The unicellular principle of correlation between the number of genes and degree of structural complexity is not valid for metazoans. The early expectations of geneticists that the number of genes in higher metazoans would be larger than in lower metazoans did not prove to be true. Genome sequencing of various metazoan organisms has shown that no relationship between the number of genes or the size of the genome and the complexity or the position of metazoans in the tree of life exists. A human organism has about 20-25,000 genes in its genome (International Human Genome Sequencing Consortium, 2004), i.e. only little more than, the fruit fly (~20,000), a lower invertebrate organism but less than a sheep or a chimpanzee and, even more surprisingly, half of the genes of a unicellular eukaryote (Aury et al., 2006).

This evidence leads to the question: if the degree of metazoan structural and functional complexity, and the evolutionary progress related to it, depends not on the number of genes, what it may depend on?

Before entering into a discussion on this topic, it is necessary to theoretically argue why the number of genes in metazoans, contrary to what is observed in unicellulars, is not related to the degree of their functional and structural complexity. Why a correlation between evolution of genes and structural complexity does not exist in metazoans?

One of the biggest challenges for the transition to the multicellular organization is the coordination of the activity cells that would enable the emergence and maintenance of the multicellular system. Individual cells would be instructed to relinquish their independent existence, show some elementary “altruism” and subject their existence to the need of maintaining the structure and function of the multicellular system to which they belong. Ultimately, their own life depends on, and is subordinate to, the life of the multicellular system.

Thus, the emerging multicellular system was confronted with another problem: generation and provision of information for the functioning of the individual cells. Obviously, this information is not in the genes inherited from their unicellular ancestors, which could not predict that their multicellular descendants some day would need some other type of information. Metazoans, and multicellular organisms in general, evolved from unicellulars, which clearly lack any “coordinating genes” for they had no cells to coordinate. Evolution does not work prophetically.

The ability of unicellulars to form colonies, loose aggregates of relatively independent cells, seems to have appeared as early as prokaryotes of the type of modern bacteria, with considerable progress shown in the eukaryotic colonies of the Volvox type. These aggregations are qualitatively different from what is normally understood to be an organism; the activity of the cells in the colony is neither coordinated nor subordinate to the “demands of the colony”.

Transition from those loose communities of cells (multicellular colonies) to the more complex multicellular structure of parazoans (porifera and parazoans) occurred no later than 600 million years ago.

Before the emergence of and eumetazoans, elements of the coordination at the level of the multicellular system evolved in Porifera. Moreover, non-genetic, epigenetic control evolved early in unicellular eukaryotes (cortical inheritance) as it will be shown later in this chapter.

Parazoans (Porifera and Placozoa) display a minimal degree of coordination and cooperation at suborganismic levels and a degree of structural integration at the level of organism, which inspired some biologists to speak of the presence of a still unidentified “neuroid” system in that group. They also display a surprising degree of cellular differentiation, which is comparable to that observed in lower eumetazoans (Cnidaria).

Axiomatically, it may be said that the development of complex structures such as a metazoan organisms of this primitive group from unicellular gametes, egg or zygote, implies the presence of a developmental program at the supracellular level, which is necessary not only for the individual development from the unicellular stage to adulthood but also for maintaining the unavoidably eroding adult structure.  What both the individual development of the metazoan organism from a unicellular state to adult and the maintenance of that structure, the homeostasis in the broad meaning of the word, have in common is that both rely on the presence of information for that normal adult structure.

For reasons discussed earlier, this information is not in genes (see chapter 1), for the only type of information contained in genes are instructions for the primary protein structure, i.e. for determining the sequence of amino acids in the polypeptide chain. All the rest, the bulk of the information for building metazoan structures is non- genetic in origin.

A cell aggregation could behave as, and evolve into, a multicellular organism only if it succeeds in meeting the following minimal requirements:

1. Create a stable internal environment that would sustain the life of all the cells throughout the multicellular system.

2. “Memorize” its own supracellular structure and function and, on this basis, set standards (set points) of the parameters of its structure and functions.

3. Continually monitor the status of its structure and function.

4. Process the input of information from the external and internal environment for detecting deviations from the normal structure and function and generate its output in the form of signaling molecules that start signal cascades for maintaining and restoring the unavoidably eroding structure and functions of the organism.

5. Transmit to the germ cells its information on the species-specific structure and function.

The above functions are essentially the functions of a control system.

It seems that the first multicellular systems capable of meeting all the above requirements and enter the path of the evolutionary progress emerged some 550 to 540 million years ago, during the Cambrian explosion. This seems to have roughly coincided with the differentiation of the nerve cell, the resulting nerve net, and the CNS (central nervous system). At this juncture metazoans succeeded in evolving the epigenetic system capable of generating and storing the huge amounts of epigenetic information necessary for erecting their extremely complex structure.

The ICS evolved out of the necessity to encode and remember the extremely complex metazoan structure arising from the precise spatial arrangement of billions to trillions of cells of tens to hundreds of different types.

The CNS/neural net serves as controller of the integrated system of control (ICS) in metazoans (see chapter 1).

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Unicellulars on the Verge of Multicellularity

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Unicellular Antecedents of Metazoan Life

 

From an evolutionary point of view, the emergence of metazoans may be considered a natural result of the ~2.5 billion years evolution  of unicellular life and accumulated “evolutionary experience and wisdom”. In a specific meaning, Protista was pregnant with multicellular life. Primitive multicellulars used differentiated cells, instead of molecules, as building blocks of their structures, tissues and organs. Just as unicellulars use different macromolecules in molding their organelles, multicellulars use differentiated cells as building blocks for erecting their structure and have to produce these building blocks starting from a single initial cell (an egg cell or zygote) Differentiated metazoan cells adopt different morphologies and specialize to perform different physiological and structural functions, despite the fact that they are genetically identical. Division of labor between differentiated cells in metazoans has its counterpart in  a “division of labor” at the molecular level in unicellulars.

 

 

Unicellular Premises of Coordination of Cell Activity in Metazoans

 

If one would accept the prevailing idea that metazoans are monophyletic, then the last common ancestor of Porifera and eumetazoans, the Urmetazoa, has been in possession of

 

nearly all developmental gene families used by living animals and that these families evolved before metazoan cladogenesis. (Degnan, 2006)

 

A crucial condition for evolution of the metazoan structure has been establishment in unicellulars of a link between the extracellular stimuli with specific signal transduction pathways, which in metazoans are related to the cell differentiation, such as tyrosine kinase pathway, TGF-beta and Wnt pathways. Some biologists believe that these pathways could be activated by morphogen gradients (Degnan et al., 2005) but this is very unlikely because such gradients could not determine the intricate and convoluted patterns of different cell types in developing metazoan tissues and organs. The presence of signal transduction pathways in the immediate ancestor of the Urmetazoan has been an essential condition for the controlled expression of transcription factors during embryogenesis that is observed as early in the evolution of metazoan life as sponges are.

Although multicellularity evolved about one billion years ago, sponges as first metazoans in paleontological record are dated 580 million years ago, i.e. between 30 and 50 million years before the Cambrian explosion (Müller et al., 2004). Among the metazoan-specific transcription factor families expressed during sponge embryogenesis are members of POU homeobox genes, LIM-HD, Pax, Bar, Prox2, NK-2, T-box, MEF-2, Fox, Sox, and nuclear hormone receptor gene families (Degnan et al., 2005).

Vast evidence shows that many of the genes that are responsible for production of a number of vitally important molecules in unicellulars are conserved in higher metazoans. If metazoans evolved from unicellulars and if the Urmetazoan had “master” control genes, it inherited them from its unicellular ancestor. This is not just a speculation. All Hox genes in metazoans and metaphyta share a helix-loop-helix (HLH) and one or more modules containing a 180 bp DNA segment, called homeobox. But it is known that regulatory proteins in prokaryotes also contain a similar 60 amino acids (what corresponds to 180 bp in DNA) long helix-loop-helix that is found in all of their repressor molecules. Similar sequences are contained in yeast protein molecules MAT (mating type)-a1 and MAT- a2. It is noteworthy that switching on/off of each of these genes determines the morphological type of the yeast or mating type or both. In support of the hypothesis that Hox genes evolved in protists before the appearance of metazoans and metaphyta also comes from the fact that both animals and plants share “master control genes”, implying that their unicellular LCA (last common ancestor) has been in possession of at least one Hox gene.

It is assumed (based on the number of common Homeobox genes in arthropods and mammals) that the Urmetazoan had 3-5 Hox genes in a single cluster. Later on, a considerable expansion of these genes took place via gene duplication. In sponges, the number of Hox genes surprisingly decreased to 1 from a calculated 5-6 in the Urmetazoan. In arthropods their number is 8, while in mammals the Hox gene cluster has been repeatedly duplicated to form four clusters, all slightly different, with a total of 38 genes (Erwin et al., 1997).

Summarizing, we know that:

1. A unicellular homeobox domain is present in numerous transcription factors in unicellulars,

2. Unicellulars are capable of developing different morphological or mating types depending on whether one or the other of two alternative homeodomain genes is expressed,

3. The Urmetazoan had no one or two Hox genes but at least 5 of them (based on the number of common homeobox genes found in extant animals and plants), and

4. Metaphyta and Metazoa share common Hox genes inherited from their common ancestor, which has been a unicellular.

Hox genes evolved from one (or a few) primitive Hox gene(s) that probably appeared in unicellulars ~1 billion year ago (Lappin et al., 2006). Evolving by gene duplication, in most extant metazoans, Hox genes in extant metazoans are found in gene clusters (figure 13.2).

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