Did detoxification processes cause complex life to emerge?
Abstract
Excess oxygen is toxic for many cells and cell function can be disrupted by calcium, even if present in small amounts. Cells avoid the toxic effects of these substances by excreting oxygen-rich or Ca-containing molecules. The origin of macroscopic multi-celled animals (metazoans) can be attributed to the excretion of oxygen-rich collagen molecules (or their precursors) at a time when the seas were for the first time both oxygenated and sufficiently loaded with phosphorus for the energy (ATP) requirements of sizable metazoans. With subsequent increase of Ca in the marine environment, hard parts of CaCO3 were produced. Excretion of oxygen in combination with abundant phosphorus permitted phosphate biomineralization. In this view, the most informative biological development during the late Neoproterozoic was not the emergence of metazoans but the initial construction of viable tissues. When tissue integrity is lost, whether due to low oxygen, collagen failure, injury, chemical insult or other reasons, individual cells are released from tissue-constraints. To survive, they may then revert to unicellular life-styles that emphasize cellular proliferation and variation. When this occurs in metazoans, the result may be cancer.
Keywords
The emergence of complex multicellular life, and of marine animals equipped with shells and other hard parts, occurred during times when, with one notable exception, the oxygen content of the seas was generally rising (Des Marais et al. 1992). These and other imperfectly understood evolutionary developments occurred when the concentration of oxygen, and subsequently of calcium, reached levels that were toxic to certain single celled eukaryotes. These creatures then excreted diverse oxygen-rich molecules by activation and modification of an already ancient detoxification mechanism.
Developments during these times, listed here in their approximate order, include the first appearances in the fossil record of:
•
animal embryos lacking indications of epithelial development, found in shallow-water phosphate beds deposited ~635–551 million years ago (Ma) (Hagadorn et al. 2006),
•
very small soft-bodied metazoans dated ~600–580 Ma (Chen et al. 2004),
•
the Ediacara, ~575–542 Ma, soft-bodied and presumably collagen-poor creatures lacking well-defined symmetry, perhaps grown directly from blastulas without undergoing full or familiar gastrulation-style cell rearrangement (Saul 2007),
•
tracks, trails and pellet traces (‘trace fossils’),
•
•
short linear or zigzag U-shaped burrows in firm clay with bilobed or trilobed lower surfaces, dated close to the Ediacaran–Cambrian boundary (Dzik 2005),
•
trace-fossil assemblages influenced by the concentration of oxygen in both water column and unconsolidated sediments, from the early Cambrian (Parcha et al. 2005),
•
cylindrical chambers open to the surface (Dzik 2005),
•
worm-tubes lined with mica flakes (Onuphionella; Spiroscolex) in the earliest or early Cambrian,
•
unicellular eukaryotes that agglutinated sand grains (Knoll & Lipps 1993),
•
unicellular eukaryotes that secreted calcium carbonate (Ridgwell et al. 2003),
•
small shelly fragments derived from multielement skeletons, and debris from corals, archaeocyathids and other metazoans with radial symmetry as well as remains of molluscs, arthropods and other creatures with bilateral symmetry, marking the Ediacaran–Cambrian transition at 542 ± 1.0 Ma,
•
diverse multicelled creatures equipped with mineralized spicules, external sclerites, ‘teeth’, carapaces and reinforcements, with individual taxa believed to have acquired biomineralization independently (Porter 2007). These hard parts were constructed of aragonite (CaCO3), calcite (also CaCO3), phosphate (most commonly as hydroxylapatite, Ca5(PO4)3(OH)), chitin ((C8H13O5N)n), silica (SiO2·nH2O) (Signor & Lipps 1992), compact collagen fibres (Simkiss & Wilbur 1989) and agglutinated sand (Culver 1991; Signor & Lipps 1992),
•
and, by inference, cancer, given the presumption that cancer is not contagious across phyla and the fact that cancer affects metazoan individuals belonging to phyla which have been distinct and have had separate developmental histories at least since the Cambrian Explosion (Saul 1994; Saul 2007; Saul & Schwartz 2007).
Evidence now presented suggests that the detoxification of oxygen and of calcium can account for many or all these effects and for others as well.
Magnetite and magnetotactic navigation
By some time prior to 1.9 billion years ago (Ga), certain bacteria had acquired the ability to precipitate iron in the form of magnetite, Fe3O4, and this ability was subsequently widely acquired among various anaerobic prokaryotes. Possible benefits that have been suggested include the storage of Fe for future metabolic use, the sequestration of toxic quantities of Fe, and use as magnets to sense the vertical component in the Earth's magnetic field and thus to aid in navigating up and down.
Living bacteria incorporating linear chain-like accumulations of grains of Fe3O4 are commonly found in sharp oxic–anoxic transition zones where torque on the chain provides a magnetotactic ability that enables them to flee downwards when encountering toxic concentrations of oxygen (Fenchel & Finlay 1995; Johnsen & Lohmann 2008). The tightly defined habitat of such bacteria and their generally low oxygen tolerance suggest yet another possible origin for biogenic magnetite, namely, as a detoxification and sequestration product of oxygen by prokaryotic anaerobes in times when Fe was abundantly available.
Biogenic magnetite grains with comparable characteristics have also been found in certain flagellates (euglenoid algae) and in salmon, pigeons and humans. Their utility, if any, in the flagellates and metazoans is not known but their presence suggests that the prokaryotic mechanism or mechanisms employed to sequester Fe3O4 was at some point or points also acquired by eukaryotes.
Collagen and cancer
Complex multicelled animals with differentiated cells (metazoans) could not have emerged until the oxygen level in the oceans had attained some particular threshold (Nursall 1959). Yet since multicelled animals require molecules of the collagen family in order to form coherent tissues, and since collagen-family molecules require molecular oxygen (Towe 1981), the threshold in question must have been the level of O2 that permitted the formation of collagen for the construction of physically stable tissues (Saul 2007; Saul & Schwartz 2007).
Cancer can then be understood as a consequence of the failure of collagen to maintain the functional integrity of a metazoan tissue whether as a consequence of low oxygen or other circumstances (Saul & Schwartz 2007). Following tissue failure, individual cells may be partly or completely released from essential metazoan constraints (Sonnenschein & Soto 1999; Saul & Schwartz 2007). If such cells then survive and are not restored to their home tissue, they may proliferate and vary – the two Darwinian imperatives – in ways that are incompatible with the metazoan requirement that individual cells cooperate with one another (Saul 1994; Sonnenschein & Soto 1999; Saul & Schwartz 2007).
Primary cancer is a pathology of tissues that causes the release of cells from metazoan constraints (Sonnenschein & Soto 1999; Saul & Schwartz 2007). Released cells proliferate and vary, and those that survive may travel within the individual metazoan. On subsequent anchoring at other tissue sites, descendants of these cancer cells may cause secondary cancers (Saul 2007).
Oxygen and oxygen toxicity
Our record of life starts ~3.9–3.5 Ga in a world in which molecular oxygen, O2, was very scarce though not entirely absent and it was in these chemical surroundings that many fundamental metabolic pathways were established. Around 2.9–2.7 Ga, cyanobacteria (formerly called ‘algae’ and commonly referred to as ‘pond scum’) began to harness sunlight to photosynthesize CO2 and H2O into carbohydrates, generating free oxygen as a waste product. This oxygen may not have begun to accumulate immediately, however, for it would have been rapidly consumed by reducing gasses issued by undersea volcanoes (Kump & Barley 2007). A period of fluctuating oxygen conditions ensued until stabilization of the cratons (Kump & Barley 2007) at the Archaean–Proterozoic transition, ~2.5 Ga. At that time, land-based flood-basalt volcanism, which occurs at higher temperatures and produces fewer reducing gasses than submarine volcanism, greatly increased in importance and thereby initiated the Earth's modern-style oxygen regime (Kump & Barley 2007).
With time, the oxygen content of the seas rose (with at least one interruption), forcing marine life to contend with environment change. As the level of oxygen increased, thresholds of toxicity were occasionally crossed as a consequence of the highly reactive nature of free oxygen and many of its derivative molecules, and at times certain unicells would have been exposed to what was for them a toxic environment.
Survival in a toxic environment and collagen
If they were to survive, these unicellular eukaryotes would have had to seek shelter in zones with lower concentrations of O2 (by burrowing, for example; or by entering a cell with a higher tolerance for oxygen); by constructing domains with less exposure to O2 (by clustering together, for example, as do many anaerobic ciliates when placed in oxygenated water (Fig. 1); by becoming facultative aerobes; or by developing detoxification mechanisms. These mechanisms and strategies were not mutually exclusive.
One detoxification mechanism would have been the shedding of oxygen-rich molecules. At the outset diverse easy-to-manufacture oxygen-rich substances, apparently including Fe3O4, would have been shed but with time, natural selection would favour molecules that were the least costly to shed and/or the most useful once produced. By the time of the appearance of the first metazoans, such molecules had come to include members of the collagen family, for collagen, which is essential for the formation of tissues, is present in all metazoans. Among the characteristics of collagen-family molecules are:
•
the absolute requirement of molecular oxygen (O2) for their formation (Towe 1981),
•
their repetitive structure, with periodic spacings that vary according to the particular variety of collagen,
•
their accumulation in extracellular space,
•
production in great quantities,
•
their presence in all metazoans, including sponges, and
•
their apparent total absence in unicellular eukaryotes (protists) (Towe 1981).
As noted, collagen could not have been formed until the availability of molecular oxygen had exceeded some minimal threshold (Towe 1981; Saul & Schwartz 2007). Yet just prior to the appearance of large numbers of metazoans during the main phase of the Cambrian Explosion around 520 Ma), the level of oxygen in the seas was actually falling (Des Marais et al. 1992; Squire et al. 2006). This indicates that the threshold for the formation of collagen had been passed well before, perhaps around 575 Ma when the first Ediacara-type megafossils appeared (Knoll et al. 2006), though most probably not before the end of the Gaskiers glaciation, 580 ± 1 Ma, at which time the deep ocean was anoxic (Canfield et al. 2007). Additional arguments indicate that by the latest Precambrian certain burrowing creatures and others possessed structures with properties akin to those conferred by collagen (but unlike chitin) (Dzik 1999). Yet the complexity and perhaps the size of multicelled creatures in Ediacaran times had been constrained:
•
perhaps because the quality of collagen was poor, either because of chemical constraints or lack of sufficient time for selective winnowing (Saul & Schwartz 2007),
•
perhaps because the mechanism of gastrulation had not yet evolved among embryo-like animals (Saul 2007), and
•
by other factors, presumably including the limits to the efficiency of animals lacking well defined symmetry or metameres.
Yet behind any and all such considerations is the possibility that creatures in these times were starved for nutrients, specifically for the phosphorus required in order to form the energy-currency molecule ATP (adenosine 5′-triphosphate) in sufficient quantities to maintain active metazoans of non-microscopic sizes.
Phosphorus and the Pan-African event
Exceptional quantities of phosphorus may have become available around this time, derived from the erosion of what Squire et al. (2006) call the ‘Transgondwanan Supermountain’, an extraordinary topographic feature formed by the oblique collision of East and West Gondwanaland in late Pan-African times (Squire et al. 2006). Its dimensions were 8000+ km long by 1000+ km wide and it extended from what would become southern Israel through northeastern and eastern Africa, Madagascar, west Australia and into Antarctica. Erosion of this mountain was quantitatively and qualitatively unique for it occurred in conditions of high rainfall at a time when soil biota may have already ‘evolved to the point that they could accelerate chemical weathering’ (Squire et al. 2006, p. 127), but before the appearance of rooted plants that might retain the soil (Squire et al. 2006). The consequence was a uniquely large and rapid flux of phosphorous into the oceans commencing about 650 Ma, along with a near simultaneous influx of Fe, Sr, Ca and bicarbonate ions (Squire et al. 2006).
The concurrent increase in the 87Sr/86Sr ratio in marine sediments (Squire et al. 2006) during this episode contrasts with the lack of a similar increase during the earlier Grenville orogenic cycle at 1200–900 Ma (Squire et al. 2006). For whereas strontium, whose residence time in the ocean is 2.5 × 106 years (Squire et al. 2006), had been cleared from the oceans during the Grenville cycle, the flux of Sr around 650 Ma had evidently been too great to be cleared (Squire et al. 2006). This argument has been extended to phosphorus, whose oceanic residence time is some 25 times shorter than that of strontium (Squire et al. 2006), thereby providing an explanation for the apparently unprecedented deposition of substantial phosphate beds in the late Neoproterozoic, a consequence of the influx of phosphorous far in excess of worldwide metabolic uptake.
On its own, the phosphorous provided by the erosion of the Transgondwanan Supermountain does not adequately explain all the ‘first appearances’ evoked earlier because events during these 200–300 Ma possessed a fine structure spread over a longer period than the presumed erosion of the Supermountain. In addition to Snowball episodes, events during this interval included a series of oceanic anoxic events between 800 and 600 Ma (Donnelly et al. 1990) and a double phosphogenic event close to the Precambrian–Cambrian boundary (Brasier 1990). Thus, rather than evoking the extraordinary erosion of the Supermountain as a one-time solitary event, it seems necessary to consider the several closely spaced continent-to-continent collisions during Pan-African times (Veevers 2003), their respective mountain-building and erosional sequels, and their culmination with the uplift and erosion of the Transgondwanan Supermountain. ‘Pan-African’ is the name given to this multiphased happening which, despite its name, affected all of Gondwanaland, not just Africa (Veevers 2003). The Pan-African Event was itself unique (Veevers 2003), and the Pan-African Supermountain doubly so.
Calcium and calcium detoxification
Oxygen had first become abundant and then phosphorous. Yet excess oxygen is toxic to many creatures and, as deduced here, was excreted by the unicellular ancestors of the metazoa in the form of the ‘oxygen expensive’ (Towe 1970, p. 781) molecules of the collagen family (Saul 2007; Saul & Schwartz 2007).
The formation of collagen was a necessary precursor for the formation of animalian tissues for the early metazoans, all of which were small and soft-bodied. By ~542 Ma, phosphorus had provided the energy that enabled them to grow larger. But in the times that followed, from 543 to 515 Ma, the calcium content of seawater increased by a factor of three (Squire et al. 2006) and calcium is also toxic. Indeed, ‘the calcium ion is pharmacologically one of the most disruptive substances for normal cell function’, with the intracellular concentrations of calcium ions carefully regulated (Simkiss 1977, p. 199). Thus salt-water biofilms of the cholera bacteria Vibrio cholerae disintegrate when a calcium-binding compound is added to their environment, an effect that does not occur when ions other than those of calcium are similarly bound (Kierek & Watnick 2003). Expressed more broadly, ‘calcium makes germs cluster’ (Harder 2003, p. 293).
As ‘a toxic ion that must be removed from most cells’ (Simkiss 1977, p. 199), calcium accumulates ‘extracellularly’ and the occurrence of calcium deposits may therefore represent a form of ‘detoxification’ (Simkiss 1977, p. 199). Hence ‘biomineralization may be a cellular detoxification mechanism’ (Simkiss 1977, p. 199), and the removal of calcium by a wide variety of metazoans by precipitation in the form of highly insoluble intracellular granules ‘may be energetically more economical than pumping it out of the cells into a supersaturated body fluid’ (Simkiss 1977, p. 199).
When oxygen and calcium are simultaneously present in toxic amounts, the two may be inexpensively excreted together in molecules of CaCO3, with taxa that manufactured aragonite appearing earlier (Porter 2007). Here the notion of ‘inexpensive’ is contingent on the concurrent availability of carbon, just as ‘inexpensive’ in the earlier Fe-rich seas had permitted or favoured or required anaerobes to sequester oxygen as magnetite, Fe3O4.
A published survey of calcium deposition in diverse invertebrate tissue samples indicates that Ag, Al, B, Ba, Cd, Co, Cr, Fe, Mg, Mn, Ni, Pb, Si, Sr and zinc phosphate have been detected within Ca-rich granules (Simkiss 1977). These substances are present in widely different ratios from one sample to another, apparently reflecting the toxins to which individual creatures had been exposed. A generalized excretionary mechanism is thus indicated, a mechanism by which undesired cations can be eliminated in conjunction with an oxide, carbonate, phosphate, oxalate or other oxygen-rich anion. In this view, cases of ossified metastases in muscles and other soft tissues (Geukens et al. 2001) may be attributed to a multistep dysfunction of an ancient system for the detoxification and sequestration of oxygen.
The evident adaptability of this ancient mechanism suggests that it may have been co-opted for additional biological functions and, likewise, that its dysfunction may be implicated in pathologies other than cancer. It also supports the notion that haemoglobin may have originally functioned as an oxygen scavenger (Minning et al. 1999).
Silica and calcium: common mechanisms in biomineralization
Hard parts composed of hydroxylapatite, Ca5(PO4)3(OH), or other phosphate minerals first appear towards earliest Cambrian times and may reflect an abundance or bio-surplus of phosphorus. Something similar may be said of the slightly earlier appearance of hard parts of silica, SiO2·nH2O, known only in certain protists, algae, glass sponges (Hexactinellida), and among Demospongiae possessing spicules of silica and skeletons of the collagen-like protein spongin. These chronologically early uses of silica may reflect seawater conditions in times well before the culmination of the Pan-African during which Si had been available in abundance, phosphorous was still rare, and oxygen, but not (yet) calcium, was present in toxic concentrations.
Another type of biomineralization is known among the Sclerospongiae (coralline sponges), a poorly defined group present since Cambrian times, some of whose members have spicules of aragonite or calcite which have been secreted over a siliceous base. Observations of Sclerospongiae have led to a suggestion that ‘there may be some common mechanisms in these rather different [Si- and Ca-] systems of mineralization (Simkiss & Wilbur 1989, p. 143). But since the Sclerospongiae also produce spongin, which is a phylum-specific variety of collagen (K. Towe, personal communication, 2004), collagen too may be provisionally attributed to these ‘common mechanisms’. In recent years, better-understood features of these mechanisms have been harnessed in the manufacture of hybrid materials for biocompatible medical implants, with collagen used ‘as an organic template that binds silicic acid whose condensation results in local silicification and strengthening’ (Heinemann et al. 2007, p. 1).
Conservation of biomineralizing pathways
In the course of the emergence of Ca biomineralization, aragonite or calcite, whichever was easiest to precipitate, was first employed (Porter 2007). Yet despite subsequent changes to the chemistry of the seas, ‘taxa rarely switched mineralogies’ (Porter 2007, p. 1302), thus indicating a conservation of mineralizing pathways as regards calcium. Comparable pathway conservation may have been maintained for phylum-specific and other varieties of collagen, for non-collagenous agglutinating molecules, and for chitin, (C8H13O5N)n, a material which is ‘sensitive to oxygen availability’ (Towe 1985, p. 677) for its strengthening but not its biosynthesis (Towe 1985). In investigating such matters, it will be useful, and perhaps necessary, to relate the secretion of each substance to the great numbers of biochemical mechanisms employed by organisms to detoxify reactive oxygen species and derivatives (Raymond & Segrè 2006, p. 1764).
Tissues require an exquisitely dosed supply of oxygen in order to maintain moment-to-moment ATP requirements. Changes and imbalances in this supply may initially manifest themselves in the production, weakening, alteration, aging or pathology of collagen.
Conclusion
Many of the events comprising the emergence of complex life appear to have been driven by the need for individual cells to rid themselves of toxic excesses of oxygen and calcium. This commonly involved the concurrent shedding of other elements (Fe, Si, P and C, in particular) which were available at the times oxygen, calcium or other elements reached toxic concentrations. The shedding into extracellular space of oxygen-expensive molecules of the collagen family induced tissue-like structures to come into being, necessitated cell-to-cell cooperation, and led to the emergence of the metazoa. The emergence of complex animals with mineralized hard parts followed as a consequence of the periodic structure of molecules of the collagen family whose regularly spaced anchor-points were well suited to serve as templates or guides for the epitaxial deposition of diverse minerals.
Acknowledgements
I thank Arthur J. Boucot, Tom Fenchel, Bland J. Finlay, John C. Harshbarger, George Mayer, Susannah Porter, A.V. Sankaran, Laurent Schwartz, John B. Southard, Rick Squire and Kenneth M. Towe for their help and encouragement.
References
Brasier, M.D. 1990: Phosphogenic events and skeletal preservation across the Precambrian-Cambrian boundary interval. In Notholt, A.J.G. & Jarvis, I. (eds): Phosphorite Research and Development, volume 52, 289–303. Geological Society [London] Special Publication. Geological Society of London, London, UK.
Canfield, D.E., Poulton, S.W. & Narbonne, G.M. 2007: Late-Neoproterozoic deep-ocean oxygenation and the rise of animal life. Science 315, 92–95.
Chen, J.-Y., Bottjer, D.J., Oliveri, P., Dornbos, S.Q., Gao, F., Ruffins, S., Chi, H.-M., Li, C.-W. & Davidson, E.W. 2004: Small bilaterian fossils from 40 to 55 million years before the Cambrian. Science 305, 218–222.
Culver, S.J. 1991: Early Cambrian foraminifera from West Africa. Science 254, 689–691.
Des Marais, D.J., Strauss, H., Summons, R.E. & Hayes, J.M. 1992: Carbon isotope evidence for the stepwise oxidation of the Proterozoic environment. Nature 359, 605–609.
Donnelly, T.H., Shergold, J.H., Southgate, P.N. & Barnes, C.J. 1990: Events leading to global phosphogenesis around the Proterozoic/Cambrian boundary. In Notholt, A.J.G. & Jarvis, I. (eds): Phosphorite Research and Development. volume 52, 273–287. Geological Society [London] Special Publication, Geological Society of London, London, UK.
Dzik, J. 1999: Organic membranous skeleton of the Precambrian metazoans from Namibia. Geology 27, 519–522.
Dzik, J. 2005: Behavioral and anatomical unity of the earliest burrowing animals and the cause of the ‘Cambrian Explosion’. Paleobiology 31, 503–521.
Fenchel, T. & Finlay, B.J. 1995: Ecology and Evolution in Anoxic Worlds, 276 pp. Oxford University Press, Oxford, UK.
Geukens, D.M., Vande Berg, B.C., Malghem, J., De Nayer, P., Galant, C. & Lecouvet, F.E. 2001: Ossifying muscle metastases from an esophageal adenocarcinoma mimicking myositis ossificans. American Journal of Roentgenology 176, 1165–1166.
Hagadorn, J.W., Xiao, S.-H., Donoghue, P.C.J., Bengtson, S., Gostling, N.J., Pawlowska, M., Raff, E.C., Raff, R.A., Turner, F.R., Yin, C.-Y., Zhou, C.-M., Yuan, X.-L., McFeely, M.B., Stampanoni, M. & Nealson, K.H. 2006: Cellular and subcellular structure of Neoproterozoic animal embryos. Science 314, 291–294.
Harder, B. 2003: Calcium makes germs cluster: ion dilution leads cholera bacteria to disperse. Science News 164, 293–294.
Heinemann, S., Ehrlich, H., Knieb, C. & Hanke, T. 2007: Biomimetically inspired hybrid materials based on silicified collagen. International Journal of Materials Research 98, 1–7.
Johnsen, S. & Lohmann, K.J. 2008: Magnetoreception in animals. Physics Today 61, 29–35.
Kierek, K. & Watnick, P.I. 2003: Environmental determinants of Vibrio cholerae biofilm development. Applied and Environmental Microbiology 69, 5079–5088.
Knoll, A.H. & Lipps, J.H. 1993: Evolutionary history of prokaryotes and protists. In Lipps, J.H. (ed.): Fossil Prokaryotes and Protists, 19–29. Blackwell Scientific, Boston, Massachusetts.
Knoll, A.H., Walter, M.R., Narbonne, G.M. & Christie-Blick, N. 2006: The Ediacaran period: a new addition to the geologic time scale. Lethaia 39, 13–30.
Kump, L.R. & Barley, M.E. 2007: Increased subaerial volcanism and the rise of atmospheric oxygen 2.5 billion years ago. Nature 448, 1033–1036.
Minning, D.M., Gow, A.J., Bonaventura, J., Braun, R., Dewhirst, M., Goldberg, D.E. & Stamler, J.S. 1999: Ascaris haemoglobin is a nitric oxide-activated ‘deoxygenase’. Nature 401, 497–502.
Nursall, J.R. 1959: Oxygen as a prerequisite to the origin of metazoa. Nature 183, 1170–1172.
Parcha, S.K., Singh, B.P. & Singh Birendra P. 2005: Palaeoecological significance of the ichnofossils from the Early Cambrian succession of the Spiti Valley, Tethys Himalaya, India. Current Science 88, 158–162.
Porter, S.M. 2007: Seawater chemistry and early carbonate biomineralization. Science 316, 1302.
Raymond, J. & Segrè, D. 2006: The effects of oxygen on biochemical networks and the evolution of complex life. Science 311, 1764–1767.
Ridgwell, A.J., Kennedy, M.J. & Caldeira, K. 2003: Carbonate deposition, climate stability, and Neoproterozoic ice ages. Science 302, 859–862.
Saul, J.M. 1994: Cancer and autoimmune disease: a Cambrian couple? Geology 22, 5.
Saul, J.M. 2007: Origin of the phyla and cancer. Lethaia 40, 359–363.
Saul, J.M. & Schwartz, L. 2007: Cancer as a consequence of the rising level of oxygen in the Late Precambrian. Lethaia 40, 211–220.
Signor, P.W. & Lipps, J.H. 1992: Origin and early radiation of the metazoa. In Lipps, J.H. & Signor, P.W. (eds): Origin and Early Evolution of the Metazoa, 3–23, Plenum Press, New York.
Simkiss, K. & Wilbur, K.M. 1989: Biomineralization, 337 pp. Academic Press, San Diego, California.
Simkiss, K. 1977: Biomineralization and detoxification. Calcified Tissue Research 24, 199–200.
Sonnenschein, C. & Soto, A. 1999: The Society of Cells, 154 pp. Bios Scientific, Oxford, UK.
Squire, R.J., Campbell, I.H., Allen, C.M. & Wilson, C.J.L. 2006: Did the Transgondwanan Supermountain trigger the explosive radiation of animals on Earth? Earth and Planetary Science Letters 250, 116–133.
Towe, K.M. 1970: Oxygen-collagen priority and the early metazoan fossil record. Proceedings of the National Academy of Sciences, U.S.A. 65, 781–788.
Towe, K.M. 1981: Biochemical keys to the emergence of complex life. In Billingham, J. (ed.): Life in the Universe, 297–305. MIT Press, Cambridge, Massachusetts.
Towe, K.M. 1985: A role for collagen and chitin in the early evolution of metazoans. Geological Society of America, Abstracts 16, no. 33354, p. 677.
Veevers, J.J. 2003: Pan-African is Pan-Gondwanaland: oblique convergence drives rotation during 650–500 Ma assembly. Geology 31, 501–504.
Information & Authors
Information
Published In
Copyright
Copyright © 2009 Lethaia Foundation.
All rights reserved.
History
Received: 23 December 2007
Accepted: 30 April 2008
Published online: 1 June 2009
Issue date: 1 June 2009
Authors
Metrics & Citations
Metrics
Citations
Export citation
Select the format you want to export the citations of this publication.
Crossref Cited-by
- Astrobiology: resolution of the statistical Drake equation by Maccone's lognormal method in 50 steps, International Journal of Astrobiology.
- Carbonate and cation substitutions in hydroxylapatite in breast cancer micro-calcifications, Mineralogical Magazine.
- Neoproterozoic copper cycling, and the rise of metazoans, Scientific Reports.
- Cancer Prevention and Therapy of Two Types of Gap Junctional Intercellular Communication–Deficient “Cancer Stem Cell”, Cancers.
- The Role of the Mitochondria in the Evolution of Stem Cells, Including MUSE Stem Cells and Their Biology, Muse Cells.
- The Ediacaran‐Cambrian Transition, Chemostratigraphy Across Major Chronological Boundaries.
- Hormonally active phytochemicals from macroalgae: A largely untapped source of ligands to deorphanize nuclear receptors in emerging marine animal models, General and Comparative Endocrinology.
- A New Progress of the Proterozoic Chronostratigraphical Division, Acta Geologica Sinica - English Edition.
- Evolution of Microbial Quorum Sensing to Human Global Quorum Sensing: An Insight into How Gap Junctional Intercellular Communication Might Be Linked to the Global Metabolic Disease Crisis, Biology.
- Characterisation and Testing of Bioceramic Coatings, Bioceramic Coatings for Medical Implants.
- The use of physiological solutions or media in calcium phosphate synthesis and processing, Acta Biomaterialia.
- Diet/Nutrition, Inflammation, Cellular Senescence, Stem Cells, Diseases of Aging, and Aging, Inflammation, Advancing Age and Nutrition.
- Induction of iPS Cells and of Cancer Stem Cells: The Stem Cell or Reprogramming Hypothesis of Cancer?, The Anatomical Record.
- Not all sponges will thrive in a high-CO2 ocean: Review of the mineralogy of calcifying sponges, Palaeogeography, Palaeoclimatology, Palaeoecology.
- Fossil evidence for the escalation and origin of marine mutualisms, Journal of Natural History.
- The Neoproterozoic oxygenation event: Environmental perturbations and biogeochemical cycling, Earth-Science Reviews.
- A Chronostratigraphic Division of the Precambrian, The Geologic Time Scale.
- Pre-Natal Epigenetic Influences on Acute and Chronic Diseases Later in Life, such as Cancer: Global Health Crises Resulting from a Collision of Biological and Cultural Evolution, Preventive Nutrition and Food Science.
- The gap junction as a “Biological Rosetta Stone”: implications of evolution, stem cells to homeostatic regulation of health and disease in the Barker hypothesis, Journal of Cell Communication and Signaling.