Chimpanzees as an outgroup for the examination of human dental evolution.

In the assessment of human origins, chimpanzees (Pan troglodytes, henceforth called Pan) represent the best hominoid outgroup for comparisons. Such an outgroup roots the "anatomically modern" human population cluster, or continuum. This study incorporates chimpanzees into a worldwide modern human database of quantified complete tooth variables (approximately 30 per tooth; e.g., root, pulp, enamel) in an attempt to develop a more accurate phylogeny of the hominoid continuum, with only intervening extinct hominids missing. Canonical discriminate analysis was performed mainly among Liberian common chimpanzees and global samples of humans. The first canonical variable explained 70% of the total variance and showed a tight cluster of humans, with chimpanzees as a distant outgroup. Within the human community, first non-San Bushman, sub-Saharan Africans and Andamanese, and then, close in, Australian aborigines were positioned towards Pan. Their relative orientation suggested an African human origin with the first branch within sub-Saharan Africa: sub-Saharan Africans and San Bushmen. Next, Andamanese Negritos, and then Australian aborigines, formed the early first surviving modern human lineage to leave Africa. Thin enamel and big teeth with relatively large roots characterized Pan nonmolar teeth. Humans showed a generalized sexual dimorphism for all teeth, with males having bigger teeth, bigger relative roots, and thinner enamel than females, while only Pan canines had significant and impressive sexual dimorphism. Interestingly, Pan molars were not larger than human molars. The data suggest that although hominids underwent two dental macroevolutionary events, the lineage leading to modern humans only experienced anterior tooth-size reduction. The suggested evolutionary significance of the observed total tooth variation is discussed.

Her name is "Lucy", our three-million-year-old ancestor.

Dental anthropology is a key discipline in studies to determine the evolutionary history of our hominid ancestors, to identify the origin and dispersal of modern humans, and to reconstruct the source of observed dental variation. A survey of hominid and modern human evolutionary history, emphasizing results from powerful multivariate dental morphometric methodologies, suggests a single African origin of modern humans > 150,000 years before present from a Homo heidelbergensis ancestor. A continuum among modern humanity is described, with, first, sub-Saharan Africans, then southeast Asian Negrito, and Australian aborigines at its extant root. Other interpretations of the available data are possible. Examinations of the progress of the evolution of teeth through time give significant insight into dental morphogenetics and variation, and the biology of dental evolution. The mechanisms of evolution which fashion a phenotype and the methods of molecular and dental phylogenetics are reviewed and evaluated. This is an exciting time for dental anthropology, with fascinating and challenging questions to address, but anthropologists, not dentists, dominate the field. The perspective of a dentist can meaningfully add to the dynamics of dental anthropology.

Technical note: Stafne static mandibular bone defect-further expression on the buccal aspect of the ramus.

The anatomic distribution of the Stafne static mandibular bone defect (SSBD) is extended with a description of a cavitation defect on the buccal ramus of the mandible. The anatomical placement of SSBD thus correlates precisely with the submandibular and parotid salivary glands, and gives further evidence that an increase in major salivary gland size is associated with the defect. The global latitudinal variation in the population prevalence of SSBD ranges from 10% in the tropics to virtually 0% in most of the arctic. Globally the defect directly correlates with parasite load and diversity, and may be a marker for of a history of an environment with high levels of enteric macroparasite infestation.

A new perspective of human origin and dispersals derived from the microevolution of teeth.

Recent genetic studies have heightened the expectation that the origin of modern humans will be defined, but one clear vision has yet to be developed. The study of teeth has historically been an informative means to help define human dispersals. Quantitative tooth data is presented encompassing worldwide human populations. A null hypothesis phylogeny developed from the multivariate analysis of the microevolution of the dental phenotype was interpreted to be broadly in accord with the dominant interpretation of genetic, archaeological, and other dental data by showing that the first division in the dispersion of extant humanity was within sub-Sahara Africans; i.e., San, and Western Africans and Bantu. This "out-of-Africa" interpretation of the graphical results suggests that the first modern human African emigrants not to go extinct were Southeast Asian Negritos. All Eurasians then emerged and expanded through a series of extinct antecedent populations branching from the short lineage extending from Negritos to Australian aborigines. Caucasoids were the first group to fission from this stock. Under this hypothesis, the next to have emerged were antecedent Southeast Asians, from which present Southeast Asians and then antecedent east Central Asians then diverged. Independently, people from the region of Mongolia and all Native Americans arose as daughter populations from antecedent east Central Asians. The broad outline of humanity studied here cannot disprove the equally explanatory protean multiregional hypotheses, but with the inclusion of hominids and further modern human populations either parts of the multiregional hypothesis or the outlined more linear evolutionary scenario likely can be refuted.

Does a parasite have a better chance of survival if an Inuit or a Mayan spits on it?

An earlier puzzling observation [Shields and Mann, J Craiofac Genet Dev Biol, 16:126-136, 1996] that the prevalence of a polymorphic male predominate, major salivary gland-associated, static lesion of the mandible increased exponentially from the Arctic to the Tropics was explained by both positive and negative selection (balancing) on major salivary gland endocrine and exocrine factors. Additional prevalence rates presented here identified three high prevalence high-Temperate zone cultures that were unusually exposed to alimentary parasites. A correlation between macroparasite exposure and the mandibular lesion helped refine the potential selective forces that fashioned major salivary gland size variation. The data suggests that positive selection occurred for androgen-induced enlargement of the suite of major salivary glands and consequently increased quantities of factors. Increased quantities of salivary gland biologically active factors enhance innate protection against infestation of macroparasites per se, especially gut parasites. The data further suggests that negative selection against enlarged salivary glands occurred as protection against electrolyte imbalances in electrolyte stressed environments and in females.

The origin of Europeans is not rooted in the Middle East but in southern east Asia.

The study of tooth crown variables has proven useful in the assessment of human origin and dispersal. I show that multivariate analysis of quantified total tooth structure from dental X-rays is a powerful phylogenetic methodology. From an analysis of the complex global dental phenotype ("GDP," composed of approximately 30 root, pulp, crown, and enamel variables per tooth), a representative Western European population was found to associate with Southeast Asians, while Mongolians formed a tight cluster with all Native Americans. The results suggest that either an emigrant wave, or waves, of modern humans emerged from Africa and with time segregated into at least three groups: Australian aborigines, Europeans, and Southeast Asians, or less likely due to genetic and archaeologic observations, a southern Asia origin of all modern humans from an emigrant African hominid. Both hypotheses portend an early evolution of the European genotype and support the argument that Europeans are principally derived from Upper Paleolithic hunter-gatherers, and thus Middle East Neolithic people did not have a major genetic impact on Europeans.

Dorset and Thule divergence from East Central Asian roots.

The history of the immigration of East Asians to America during the last glacial period remains controversial. In an attempt to add critical data to this problem, a large sample of whole teeth derived from Southeast Asian, Mongolian, Thule, Western Inuit, and pre-Inca (Huari) people was quantified (N = 4,507 teeth from 495 individuals; approximately 30 variables per tooth). Multivariate analysis helped establish that all Native Americans were likely derived from one ancient, extinct population that resided in the region of Mongolia (east Central Asia), and that Mongolians and Southeast Asians are two independent groups. A controversial and enigmatic Central Canadian Arctic "Thule culture Inuit" group on Southampton Island that survived until 1902 was identified as a relic, mainly Paleoeskimo Dorset community. Surprisingly, there was little, or no, indication of Dorset-to-Thule gene flow. Cumulatively, the data suggest that a small population of Paleoindian founders remained resident in Beringia, may have blocked further immigration, and were the antecedents to the Thule/Inuit. With the confluence of the Arctic and Pacific oceans at the breakup of Beringia, the resulting increased availability of marine animal food sources allowed this population to increase in size and expand throughout the eastern Arctic.

Australian aborigines represent the first branch from Eurasian antecedents: odontometric evidence.

Most genetic data suggest that Australian aborigines and Southeast Asians associate, but their relative evolutionary relationship has remained obscure. Historically, the study of tooth crown variables has been important in establishing phylogenetic relationships. Through the quantification of whole tooth structure (GDP), including root, pulp, and enamel, a likely Eurasian phylogeny emerged from a canonical discriminant analysis of the microevolution among the populations. The analysis suggested that in modern human evolutionary history, Australian aborigines are the best representative extant population (first branch) from an unknown antecedent Eurasian founder population. The next branch from the Asian-based antecedent population was Caucasoids. Within the resident antecedent East Asian population, Southeast Asians then evolved, followed by a branch that lead to antecedent east Central Asians. Mongolians and all Native Americans independently evolved from this antecedent east Central Asian population. The relatively short morphogenetic separation between two areas that have been isolated for great periods of time, i.e., Australian aborigines and Native Americans, suggests that their association is not due to gene flow.

Quantitative complete tooth variation among east Asians and Native Americans: developmental biology as a tool for the assessment of human divergence.

The quantification of total tooth structure derived from X-rays of Vietnamese, Southern Chinese, Mongolians, Western Eskimos, and Peruvian pre-Inca (Huari Empire) populations was used to examine dental divergence and the morphogenetics of change. Multivariate derived distances between the samples helped identify a quasicontinuous web of ethnic groups with two binary clusters ensconced within the web. One cluster was composed of Mongolians, Western Eskimos, and pre-Inca, and the other group consisted of the Southern Chinese and Vietnamese. Mongolians entered the quasicontinuum from a divergent angle (externally influenced) from that of the Southeast Asians. The Chinese and pre-Inca formed the polar samples of the distance superstructure. The pre-Inca sample was the most isolated, its closest neighbor being the Western Eskimos. Univariate and multivariate analyses suggested that the pre-Inca, whose ancestors arrived in America perhaps approximately 30,000 years ago, was the least derived sample. Clearly, microevolutionary change occurred among the samples, but the dental phenotype was resistant to environmental developmental perturbations. An assessment of dental divergence and developmental biology suggested that the overall dental phenotype is a complex multigenic morphological character, and that the observed variation evolved through total genomic drift. The quantified dental phenotype is greater than its highly multigenic algorithm and its development homeostasis is tightly controlled, or canalized, by the deterministic organization of a complex nonlinear epigenetic milieu. The overall dental phenotype quantified here was selectively neutral and a good character to help reconstruct the sequence of human evolution, but if the outlying homeostatic threshold was or will be exceeded in antecedents and descendants, respectively, evolutionary saltation occurs.

Heterochronic quantitative microevolution: dental divergence in aboriginal Americans.

Studies of tooth crown morphology alone have proven valuable in defining human population differentiation. We test the hypothesis that quantitative comparisons of more complex whole tooth structure may prove informative in understanding human diversity. Three disparate populations in Native American genetic history were compared: Kodiak Island Western Eskimos, Peruvian Inca Amerindians, and Southeast Asians. Enamel depth (an increasing gradient extended from Southeast Asians to the Inca) and root parameters were the most discriminating variables. The observed microevolution appears to result from variation in timing of known X-linked, Y-linked, and autosomal genes that affect either ameloblast or odontoblast differentiation. The dental traits were sexually dimorphic, the effect being more pronounced in aboriginal Americans, with male teeth having robust roots and thin enamel compared to female. Southeast Asians were isometrically related. The prominence of sexual dimorphism and the importance of sex-linked genes in the determination of the dental phenotypes suggest that sexual selection was one evolutionary force acting on early Asian populations. Subsequently, the selection appears to have been relaxed in Southeast Asians. Observed divergence of tooth shape among the populations, i.e., differences in the appropriation process of tooth primordia, was mainly the consequence of genetic drift modulating heterochronic regulators of homeotic genes.

Salivary glands and human selection: a hypothesis.

Stafne static bone defect (SSBD) of the mandible is the only described destructive bone lesion that is highly localized, nonprogressive, but nonhealing. This common defect in male is found in the region of the major salivary glands that produce a cornucopia of biologically active factors. We describe rare phenocopies caused by mandibular immobility that hold the gland in a constant position thus implicating a localized chronic "leak" of an osteoclast induction factor from the major salivary glands as the pathologic agent. This finding suggests that increased salivary gland size could simulate immobility by apposing the gland to bone, thus allowing the "leaked" factor's gradient to have an effect. In one step, the putative genetic enlargement of a critical gland that produces many factors important for survival, a broad biological vista would be available to the massive potential for both positive and negative selection. Positive selection was identified by observing a correlation between the prevalence of enhanced androgen-induced enlarge salivary glands (SSBD) as a marker, with a great preponderance of males) and the conjectured resulting increased production of immunoreactive factors, with pole-to-equator isotherm and broad ranged infection clines. Negative selection was observed among the slave ancestors of African Americans for a potential embryonic homeotic mutation causing larger salivary glands in both sexes (decreased prevalence of SSBD, with an equal sex ratio). The decreased production of saliva and electrolytes diminished the salt and water depletive effects of severe diarrhea and vomiting induced by enteric diseases, which killed many slaves. Data presented suggests that SSBD is a polymorphism and a marker of selection processes that cause variation in size, or structure, of the major salivary glands.

Locomotor phenotypes of unstimulated CD45RAhigh and CD45ROhigh CD4+ and CD8+ lymphocytes in three-dimensional collagen lattices.

The spontaneous locomotion of immunomagnetically isolated resting CD4+ and CD8+ lymphocytes in three-dimensional collagen gels was recorded by time-lapse videomicroscopy. Two-dimensional projections of the paths of randomly selected individual cells were digitized, plotted and quantitatively analysed. Among five different donors 46 +/- 10% of CD4+ and CD8+ lymphocytes (n = 180) showed initial spontaneous locomotion (individual speed 5-25 microns/min; mean speed CD4+ 5.2 +/- 3.6 microns, CD8+ 3.23 +/- 2.72 microns). Active CD4+ cells were constantly migrating for more than 4 hr, whereas CD8+ lymphocytes significantly slowed down after 60-90 min in the collagen gel (P < 0.003). Quantitative analysis of the paths indicated at least three migratory phenotypes: (1) spontaneously locomoting cells exhibiting high speed and low frequency of stopping; (2) a major non-motile fraction without significant displacement; and (3) a subpopulation within CD4+ and CD8+ cells with intermediate activity of speed and stopping. Further subtype analysis of immunomagnetically isolated CD45RAhigh/ROlow or CD45RAlow/ROhigh lymphocytes showed that more than 90% of CD4+ CD45RAhigh/ROlow cells were actively locomoting. In contrast, only 20% of the CD4+ CD45ROhigh/RAlow phenotype showed spontaneous motility to a limited degree. The data indicate that resting CD4+ and CD8+ lymphocytes comprise further locomotory subpopulation related to the expression of different CD45 isoforms.

Changes in cell three-dimensional locomotory characteristics upon expression of the EJ-ras oncogene.

Activation of the ras oncogene induces ruffling of membranes, enhances cell locomotion and has been implicated in the invasive process. We have investigated the locomotory changes of a 212 cell line due to ras activation using a novel system for determining the three-dimensional trajectories of cells migrating within collagen lattices. It was found that a small, yet statistically significant increase in cell speed resulted and that the duration of locomotory periods was prolonged in ras activated cells. These locomotory periods was prolonged in ras activated cells. These locomotory periods were cyclic in nature with a periodicity of approximately 30 min. These results are discussed in the relation to the current hypotheses concerning the molecular mechanisms involved in pseudopod kinetics.

Does a genetically determined aggressive locomotion favour the establishment of intracellular macrophage parasites?

A novel computerized methodology was used to quantify, for the first time, the 3-dimensional locomotory phenotypes of individual macrophages moving within an extracellular matrix-like hydrated collagen lattice/gel. Comparisons between two macrophage lines genetically susceptible to intracellular parasites (B10S4 and ANA-1) and two genetically resistant (B10R4 and CD2) demonstrated that Bcgs alleles consistently endowed macrophages with an outward searching and active locomotion, whereas Bcgr imparted a retrocessive phenotype. Several different macrophage pathogens may have exploited this genetically determined aggressive locomotory behavior of susceptible macrophages to allow them to rapidly enter a sanctuary.

Cavitation defects on the lingual ramus: a further expression of Stafne's defect.

Seven archaeological examples of 6,700 mandibles examined were found to have developmental cortical defects on the ramus. The defects, unusual in their position, were grossly and radiographically similar to developmental bone cavities (Stafne's) located in the sublingual region. Of the seven ramus defects, all of which were in adult males, six were in Alaskan Eskimos from Kodiak Island (N = 5) and Nelson Island (N = 1), and one was in a native American from Arkansas. Only five adult males from Finland have been reported with similar defects. A statistical examination of the metrics defining mandibular cavitation defects, along with prevalence data, suggest that the seemingly rare findings of ramus defects are an extreme manifestation of the continuum of severity of the Stafne's defect. Bilateral Stafne's defects also represent a severe manifestation.

Locomotory characteristics of fibroblasts within a three-dimensional collagen lattice: modulation by a helium/neon soft laser.

It has been postulated that low energy (soft) lasers can enhance wound healing. Considering the importance of cell locomotion in the wound healing process, we have studied the effects of a helium/neon laser upon the locomotory behaviour of a population of fibroblasts migrating within a three-dimensional hydrated collagen lattice. Statistical methods were used to quantify cell three-dimensional trajectories obtained using a computer-assisted tracking system. A two-minute exposure of embryonic fibroblasts to soft laser light decreased the speed and increased the frequency and duration of stops compared to controls. The locomotory phenotype induced in embryonic fibroblasts by the laser light resembled that of the developmentally older c20 fibroblasts, which are known to express a more mature locomotory phenotype. The relevance of these results to wound healing is discussed.

X-linked hypophosphatemia: the mutant gene is expressed in teeth as well as in kidney.

Mutation at a locus (HPDR) on the X chromosome (McKusick 30780 [HPDR1]; 30781 [HPDR2]) causes impaired renal phosphate transport, hypophosphatemia, and an associated impairment in the process of mineralization in bone and teeth (X-linked hypophosphatemia [XLH]). We measured the dental pulp profile area (PRATIO [= pulp area/tooth area]) and serum phosphorus (Pi) values in uniformly treated XLH patients (six males, 81 teeth, 1,457 Pi values; 11 females, 129 teeth, 1,439 Pi values). Serum Pi values, reflecting the metabolic environment of tooth development, were obtained by repeated measurement between 1 mo and 26 years of age during treatment. PRATIO values calculated from standardized Rinn radiographs were used as outcome measurements of tooth development in XLH patients and in age-matched controls (12 males, 100 teeth; 27 females, 275 teeth). Age-dependent serum Pi values were not different in the treated XLH males and females. In teeth forming primary dentin there was no gene dosage effect on PRATIO values apparent in subjects below 15 years of age. However, in teeth forming secondary dentin a gene dosage was found in the subjects aged 15 to 25 years: XLH male teeth (n = 65) mean +/- SD = 0.163 +/- 0.046; XLH female teeth (n = 75) mean +/- SD = 0.137 +/- 0.039; control teeth (n = 209) mean +/- SD = 0.116 +/- 0.023; (higher PRATIO values mean less development or mineralization of secondary dentin); differences in these PRATIO values (males vs. female and XLH vs. control) were significant by mixed-model analysis of variance.(ABSTRACT TRUNCATED AT 250 WORDS)

Odontometric variation among American black, European, and Mongoloid populations.

Quantified dental parameters (including root and pulp areas and shape variables) derived from periapical radiographs were used to make comparisons among a sample of American Black (8 males--124 teeth, 9 females--138 teeth), European derivative (31 males--304 teeth, 43 females--497 teeth) and Mongoloid populations (12 males--166 teeth, 19 females--252 teeth). The magnitude of sexual dimorphism within each ethnic stock was also examined. Teeth from American Black males were robust. Sexual dimorphism was unambiguous in all groups although a hierarchical order existed from the highly dichotomous American Black sample to the more homogeneous European sample. The female dental phenotype was down-scaled from their male counterparts, but not gracile in form. Easily obtained area and shape parameters derived from dental radiographs proved useful as discriminators among racial groups and the sexes. The relationships among these data lend further support to the hypothesis of an African origin of modern humans.

Time-based changes in fibroblast three-dimensional locomotory characteristics and phenotypes.

Three-dimensional locomotory trajectories have been determined for an embryonic fibroblast population and also for these cells after a 20-day period in tissue culture (C-20 cells). Differences in locomotory characteristics between these two cell populations are reported. Applying factor analysis to the distribution of angle changes between vectors in a cell's trajectory reveals the possibility that different locomotory phenotypes exist. Of the three phenotypes detected in the embryonic population only one continues in the C-20 population while a new phenotype appears in the latter. These results document changes in locomotory characteristics and phenotypes in an embryonic population with time.

Oral findings in patients with autosomal dominant hypophosphatemic bone disease and X-linked hypophosphatemia: further evidence that they are different diseases.

Oral examinations were performed on 5 patients with hypophosphatemic bone disease (HBD) (2 males and 3 females), 14 patients with X-linked hypophosphatemia (XLH), and 4 affected XLH relatives (6 males and 12 females). The control subjects were the unaffected siblings and parents of the patients and unrelated healthy, gender- and age-matched subjects. Serum phosphorus values were the same by disease type and gender in patients with HBD and XLH. They shared certain dental abnormalities, in particular pulpal necrosis and large pulp spaces. However, only patients with XLH had Class III malocclusions and mild enamel defects, and males with XLH had more severe occlusal and enamel defects than females with XLH. Different dental phenotypes are further evidence that XLH and HBD are different diseases. The dental abnormalities were not prevented by treatment, instituted early in life, which raised serum phosphorus to the near normal range.