Where did bone come from? An overview of its evolution Darja Obradovic Wagner and Per Aspenberg Linköping University Post Print N.B.: When citing this work, cite the original article. Original Publication: Darja Obradovic Wagner and Per Aspenberg, Where did bone come from? An overview of its evolution, 2011, Acta Orthopaedica, (82), 4, 393-398. http://dx.doi.org/10.3109/17453674.2011.588861 Postprint available at: Linköping University Electronic Press http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-71096 Acta Orthopaedica 2011; 82 (4): 393–398 393 Where did bone come from? An overview of its evolution Darja Obradovic Wagner1 and Per Aspenberg2 1Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany, 2Orthopedics, AIR/IKE, Faculty of Health Science, Linköping University, Linköping, Sweden Correspondence: [email protected] Submitted 10-12-07. Accepted 11-03-08 Bone is specific to vertebrates, and originated as mineralization (enamel, bone, dentine, cartilage) was controversial. While around the basal membrane of the throat or skin, giving rise to one hypothesis suggested that the four tissues all emerged tooth-like structures and protective shields in animals with a early in vertebrate evolution, the other assumed a long time soft cartilage-like endoskeleton. A combination of fossil anatomy of tissue plasticity in early mineralized skeletons which pre- and genetic information from modern species has improved our ceded differentiation processes that came later on (Tarlo 1963, understanding of the evolution of bone. Thus, even in man, there Halstead 1969). In addition, for many decades, synthesis of are still similarities in the molecular regulation of skin append- paleontological data was influenced by Ernst Haeckel’s bioge- ages and bone. This article gives a brief overview of the major netic law—that ontogeny recapitulates phylogeny—meaning milestones in skeletal evolution. Some molecular machineries that skeletons of ancestral adult vertebrates were assumed to involving members of core genetic networks and their interac- be derived from cartilage, analogous to their embryonic skel- For personal use only. tions are described in the context of both old theories and modern etons (Hall 2003). genetic approaches. Nowadays, evidence of the mineralization of tissues is often related to the repertoire of specific secretory calcium-binding phosphoprotein (SCPP) genes present in various vertebrate lineages (Kawasaki and Weiss 2003). Expression analysis Skeletal evolution: different views revealed SCPP genes and combinations of genes that are If this article had been written a decade ago, it would have mainly used in the bone and dentine, while other SCPP vari- been considerably different. Given that most primitive exam- ants were found to be used to build up enamel structures. Cur- ples of mineralization belong to extinct lineages, for a long rent studies suggest a close relationship between bone, den- Acta Orthop Downloaded from informahealthcare.com by Linkoping University on 11/10/11 time our understanding of bone evolution was entirely based tine, and enamel in terms of a mineralized-tissue continuum on the available fossil evidence. Only paleontology studies in which contemporary dental tissues have evolved from an offered the possibility of gaining some insight into the ancient ancestral continuum through lineage-specific modifications processes that led to mineralized skeleton; from the evidence (Kawasaki 2009). available, it was surmised that the vertebrates were most likely Finally, many recent reports view skeletogenesis in light of descended from amphioxus-like forms with a notochord. the evolution of distinct core gene networks that have been These were followed by jawless creatures with a cartilage-like essential to vertebrate phylogeny (Erwin and Davidson 2009). endoskeleton, reminiscent of the modern hagfish or lamprey For example, a recent search for the molecular origins of skel- (Holland et al. 2001, Meulemans and Bronner-Fraser 2007). etal development has attracted attention to the Runt family The next big event was the appearance of mineralized skeletal of genes (RUNX 1, -2, and -3). RUNX proteins regulate the parts; this presented a major evolutionary leap and led directly key factors involved in skeletogenesis. They are crucial for to the rise of the vertebrate lineage (Denison 1963, Sansom et cartilage development, and RUNX2-deficient mice lack bone al. 1992). (Ito and Miyazone 2003, Fujita et al. 2004). Together with the Given that primitive fossilized vertebral skeletons are scarce RUNX family, several more newly discovered gene networks and that their remains often contain tissues that are difficult are currently seen as central to understanding the evolution of to classify, the emergence of the four skeletal tissue types skeleton. Open Access - This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the source is credited. DOI 10.3109/17453674.2011.588861 394 Acta Orthopaedica 2011; 82 (4): 393–398 From outer to inner protection: design combined have led early vertebrates to sequester marine phosphate could with fortuitous circumstances have been the fact that accessible phosphate stores were useful So, how did mineralized tissues develop in the first place? sources of energy for active animals, and may therefore have What factors forced the first organisms to develop protective improved their metabolism (Ruben and Bennett 1980). How- shields? ever, this view of the unique chemical attributes of vertebrates Following the violent moves of tectonic plates about 1.5 affords no advantage that would not have been equally advan- billion (1.5 × 109) years ago, huge amounts of minerals, tageous to the invertebrates. including CaCO3, were washed into the oceans. This created Another possible advantage of the novel chemical composi- the possibility for its inhabitants of developing hard body tion of vertebrate skeletons might be that calcium hydroxy- parts, such as shells or spines. At first, this helped unicellu- apatite building blocks provide greater chemical stability. lar organisms to cope with excessive amounts of minerals and This may have been important, especially in the acidic envi- to prevent over-crusting. It also led to the sharp increase in ronments created after bursts or periods of intense physical the diversity of multicellular organisms (and their fossils!) a activity—conditions that are typical of most vertebrate species little more than 0.5 billion years ago, known as the “Cambrian (Ruben and Battalia 1979, Ruben and Bennett 1981). Follow- explosion” (Schopf 1994, Kawasaki et al. 2004). Furthermore, ing intense activity, vertebrates experience a depression in the the appearance of a rigid outside skeleton extended the effec- pH values of extracellular fluids, dropping in humans from a tive length of limbs, thus permitting more rapid locomotion in resting value of 7.41 to a post-activity pH of 7.15. This path- many organisms. The appearance of mineralized body parts way relies on the production of lactic acid for generation of is seen by many scientists as one of the forces that generally ATP, and enables vertebrates to attain levels of energy produc- increased the pace of animal evolution (Kumar and Hedges tion that would not be possible with aerobic metabolism alone. 1998, Kutschera and Niklas 2004). However, the release of lactic acid and decrease in extracel- As much as exoskeleton added speed to the evolution of lular pH causes a certain degree of skeletal dissociation and animal life in general and created opportunities for animals hypercalcemia. As discussed by Ruben and Bennet (1980, to expand their activity radius by using calcified extremities 1981), the magnitude of these processes would be signifi- and protection shields, it also imposed limitations, associated cantly greater if the skeleton consisted of calcitic rather than mostly with limited body size and lack of surface sensory phosphate-based material, which would necessitate a lower organs. In addition, rigid shells and shields did not allow much overall metabolism and activity. This hypothesis was investi- movement and locomotion; therefore, the next major change gated in a series of in vivo experiments with fish, where calcite in the evolution of skeleton—dislocation of mineralized skel- or hydroxyapatite crystals were implanted into different body For personal use only. eton from the outside to the inside of animal bodies, proved to parts and the animals were kept on varying exercise regimes. be a major adaptive advantage. Especially in animal lineages Subsequent analysis of fish serum and implants showed that at that later gave rise to vertebrates, the appearance of endoskel- pH 7.1 (associated with high activity), calcium concentration eton enabled the expansion of activity radius and habitation of and implant dissolution rates were considerably higher in fish entirely new environments (Bennet 1991). In addition, those with calcite implants. In summary, other biomaterial proper- developments encouraged the development of a strong mus- ties being equal, hydroxyapatite builds a more stable mineral cular system and added further adaptive values such as greater component of the skeleton than can be achieved with a calcitic overall mobility and the appearance of a regenerative and material, which is particularly important at pH ranges that are environment-sensitive