Applying an evolutionary mismatch framework to understand disease susceptibility.

Noncommunicable diseases (NCDs) are on the rise worldwide. Obesity, cardiovascular disease, and type 2 diabetes are among a long list of "lifestyle" diseases that were rare throughout human history but are now common. The evolutionary mismatch hypothesis posits that humans evolved in environments that radically differ from those we currently experience; consequently, traits that were once advantageous may now be "mismatched" and disease causing. At the genetic level, this hypothesis predicts that loci with a history of selection will exhibit "genotype by environment" (GxE) interactions, with different health effects in "ancestral" versus "modern" environments. To identify such loci, we advocate for combining genomic tools in partnership with subsistence-level groups experiencing rapid lifestyle change. In these populations, comparisons of individuals falling on opposite extremes of the "matched" to "mismatched" spectrum are uniquely possible. More broadly, the work we propose will inform our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and cultures.

Phalangeal curvature in a chimpanzee raised like a human: Implications for inferring arboreality in fossil hominins.

Arboreal primates such as chimpanzees exhibit pronounced curvature in their hand and foot phalanges, which is assumed to develop throughout life in response to mechanical loads produced by grasping and hanging from branches. Intriguingly, ancient fossil hominins also exhibit substantial phalangeal curvature, which, too, has been interpreted as a direct result of habitual arboreality during life. Here, we describe the phalangeal curvature of a chimpanzee who was raised during the 1930s in New York City to live much like a human, including by having very few opportunities to engage in arboreal activities. We show that the degree of hand and foot phalangeal curvature in this individual is indistinguishable from that of wild chimpanzees and distinct from humans. Thus, rather than being a direct effect of mechanical loads produced by lifetime arboreal activities, phalangeal curvature appears to be shaped largely by genetic factors. An important implication of this finding is that phalangeal curvature among fossil hominins is evidently best interpreted as a primitive trait inherited from an arboreal ancestral species rather than proof of engagement in arboreal activities during life.

Secular decline in limb bone strength among South African Africans during the 19th and 20th centuries.

OBJECTIVES: South African Africans have been reported to have experienced negative or null secular trends in stature and other measures of skeletal structure across the 19th and 20th centuries, presumably due to poor living conditions during a time of intensifying racial discrimination. Here, we investigate whether any secular trend is apparent in limb bone strength during the same period. MATERIALS AND METHODS: Cadaver-derived skeletons (n = 221) were analyzed from female and male South African Africans who were born between 1839 and 1970, lived in and around Johannesburg, and died between 1925 and 1991 when they were 17-90 years of age. For each skeleton, a humerus and femur were scanned using computed tomography, and mid-diaphyseal cross-sectional geometric properties were calculated and scaled according to body size. RESULTS: In general linear mixed models accounting for sex, age at death, and skeletal element, year of birth was a significant (p < .05) negative predictor of size-standardized mid-diaphyseal cortical area (a proxy for resistance to axial loading) and polar moment of area (a proxy for resistance to bending and torsion), indicating a temporal trend toward diminishing limb bone strength. No significant interactions were detected between year of birth and age at death, suggesting that the decline in limb bone strength was mainly due to changes in skeletal maturation rather than severity of age-related bone loss. DISCUSSION: Limb bone strength is thus potentially another feature of the skeletal biology of South African Africans that was compromised by poor living conditions during the 19th and 20th centuries.

Knee osteoarthritis has doubled in prevalence since the mid-20th century.

Knee osteoarthritis (OA) is believed to be highly prevalent today because of recent increases in life expectancy and body mass index (BMI), but this assumption has not been tested using long-term historical or evolutionary data. We analyzed long-term trends in knee OA prevalence in the United States using cadaver-derived skeletons of people aged ≥50 y whose BMI at death was documented and who lived during the early industrial era (1800s to early 1900s; n = 1,581) and the modern postindustrial era (late 1900s to early 2000s; n = 819). Knee OA among individuals estimated to be ≥50 y old was also assessed in archeologically derived skeletons of prehistoric hunter-gatherers and early farmers (6000-300 B.P.; n = 176). OA was diagnosed based on the presence of eburnation (polish from bone-on-bone contact). Overall, knee OA prevalence was found to be 16% among the postindustrial sample but only 6% and 8% among the early industrial and prehistoric samples, respectively. After controlling for age, BMI, and other variables, knee OA prevalence was 2.1-fold higher (95% confidence interval, 1.5-3.1) in the postindustrial sample than in the early industrial sample. Our results indicate that increases in longevity and BMI are insufficient to explain the approximate doubling of knee OA prevalence that has occurred in the United States since the mid-20th century. Knee OA is thus more preventable than is commonly assumed, but prevention will require research on additional independent risk factors that either arose or have become amplified in the postindustrial era.

Secular trends in cranial size and shape among black South Africans over the late 19th and 20th centuries.

BACKGROUND: Previous studies of secular change in cranial size among black South Africans have produced conflicting results. AIM: We re-examined cranial size change in this population during the 19th and 20th century by evaluating its relationship with individual year-of-birth, and the significance of trends among eight decennial cohorts. SUBJECTS AND METHODS: This study is based on 102 male and 89 female adults born between 1865 and 1959. Linear regressions were employed to evaluate possible relationships between year-of-birth and cranial dimensions; ANOVAs were used to evaluate the significance of long-term trends among decennial cohorts. RESULTS: No analysis revealed a secular change in cranial length in either sex; however, the ANOVA for cranial length in the combined sex sample was significant. There is no secular trend in female cranial breadth, but males display a negative trend in this dimension. This results in a secular trend for increased male dolichocephaly. CONCLUSIONS: The factors that underlie the negative secular trend in male cranial breadth and the absence of a secular trend in overall cranial size in this population are unclear. Nevertheless, these observations accord with findings related to stature and long bone strength in this population and are consistent with observations for other sub-Saharan African populations.

Knee osteoarthritis risk in non-industrial societies undergoing an energy balance transition: evidence from the indigenous Tarahumara of Mexico.

Non-industrial societies with low energy balance levels are expected to be less vulnerable than industrial societies to diseases associated with obesity including knee osteoarthritis. However, as non-industrial societies undergo rapid lifestyle changes that promote positive energy balance, individuals whose metabolisms are adapted to energetic scarcity are encountering greater energy abundance, increasing their propensity to accumulate abdominal adipose tissue and thus potentially their sensitivity to obesity-related diseases. OBJECTIVES: Here, we propose that knee osteoarthritis is one such disease for which susceptibility is amplified by this energy balance transition. METHODS: Support for our hypothesis comes from comparisons of knee radiographs, knee pain and anthropometry among men aged ≥40 years in two populations: Tarahumara subsistence farmers in Mexico undergoing the energy balance transition and urban Americans from Framingham, Massachusetts. RESULTS: We show that despite having markedly lower obesity levels than the Americans, the Tarahumara appear predisposed to accrue greater abdominal adiposity (ie, larger abdomens) for a given body weight, and are more vulnerable to radiographic and symptomatic knee osteoarthritis at lower levels of body mass index. Also, proportionate increases in abdomen size in the two groups are associated with greater increases in radiographic knee osteoarthritis risk among the Tarahumara than the Americans, implying that the abdominal adipose tissue of the Tarahumara is a more potent stimulus for knee degeneration. CONCLUSIONS: Heightened vulnerability to knee osteoarthritis among non-industrial societies experiencing rapid lifestyle changes is a concern that warrants further investigation since such groups represent a large but understudied fraction of the global population.

Experimental evidence that physical activity affects the multivariate associations among muscle attachments (entheses).

The morphology of entheses (muscle/tendon attachment sites) on bones is routinely used in paleontological and bioarcheological studies to infer the physical activity patterns of ancient vertebrate species including hominins. However, such inferences have often been disputed owing to limitations of the quantitative methods commonly employed and a lack of experimental evidence demonstrating direct effects of physical activity on entheseal morphology. Recently, we introduced a new and improved method of quantifying and analyzing entheseal morphology that involves repeatable three-dimensional measurements combined with multivariate statistics focused on associations among multiple entheses. Here, to assess the validity of our method for investigating variation in entheseal morphology related to physical activity patterns, we analyzed femora of growing turkeys that were experimentally exercised for 10 weeks on either an inclined or declined treadmill or served as controls (N=15 individuals, 5 per group). Our multivariate approach identified certain patterns involving three different entheses (associated with the gluteus primus, medial gastrocnemius, vastus medialis and adductor magnus muscles) that clearly differentiated controls from runners. Importantly, these differences were not observable when comparing groups within each of the three entheseal structures separately. Body mass was not correlated with the resulting multivariate patterns. These results provide the first experimental evidence that variation in physical activity patterns has a direct influence on entheseal morphology. Moreover, our findings highlight the promise of our newly developed quantitative methods for analyzing the morphology of entheses to reconstruct the behavior of extinct vertebrate species based on their skeletal remains.

Locomotor constraints favour the evolution of the human pygmy phenotype in tropical rainforests.

The convergent evolution of the human pygmy phenotype in tropical rainforests is widely assumed to reflect adaptation in response to the distinct ecological challenges of this habitat (e.g. high levels of heat and humidity, high pathogen load, low food availability, and dense forest structure), yet few precise adaptive benefits of this phenotype have been proposed. Here, we describe and test a biomechanical model of how the rainforest environment can alter gait kinematics such that short stature is advantageous in dense habitats. We hypothesized that environmental constraints on step length in rainforests alter walking mechanics such that taller individuals are expected to walk more slowly due to their inability to achieve preferred step lengths in the rainforest. We tested predictions from this model with experimental field data from two short-statured populations that regularly forage in the rainforest: the Batek of Peninsular Malaysia and the Tsimane of the Bolivian Amazon. In accordance with model expectations, we found stature-dependent constraints on step length in the rainforest and concomitant reductions in walking speed that are expected to compromise foraging efficiency. These results provide the first evidence that the human pygmy phenotype is beneficial in terms of locomotor performance and highlight the value of applying laboratory-derived biomechanical models to field settings for testing evolutionary hypotheses.

Inter-ray variation in metatarsal strength properties in humans and African apes: Implications for inferring bipedal biomechanics in the Olduvai Hominid 8 foot.

When measured as a ratio of mean midshaft diameter to bone length, the OH 8 fossil hominin foot exhibits a metatarsal (Mt) robusticity pattern of 1 > 5 > 3 > 4 > 2, which differs from the widely perceived "common" modern human pattern (1 > 5 > 4 > 3 > 2); African apes generally exhibit a third pattern (1 > 2 > 3 > 4 > 5). Largely because of the relative ranking of Mt2 and Mt5, OH 8 metatarsals structurally resemble the pattern exhibited by bipedal humans more than the pattern of quadrupedal and climbing African apes. Considering only these three phenotypes, however, discounts the potentially important functional implications of variation in modern human (and African ape) metatarsal robusticity patterns, suggesting that they are not useful for interpreting the specific biomechanics of a bipedal gait in fossils (i.e., whether it was modern human-like or not). Using computed tomography scans to quantify metatarsal midshaft cross-sectional geometry in a large sample of Homo (n=130), Gorilla (n=44) and Pan (n=80), we documented greater variation in metatarsal robusticity patterns than previously recognized in all three groups. While apes consistently show a 1 > 2 > 3 > 4 > 5 pattern in our larger sample, there does not appear to be a similarly precise single "common" human pattern. Rather, human metatarsals converge towards a 1 > 4/5 > 2/3 pattern, where metatarsals 4 and 5, and metatarsals 2 and 3, often "flip" positions relative to each other depending on the variable examined. After reassessing what a "common" human pattern could be based on a larger sample, the previously described OH 8 pattern of 1 > 5 > 3 > 4 > 2 is only observed in some humans (<6%) and almost never in apes (<0.5%). Although this suggests an overall greater similarity to (some) humans than to any ape in loading of the foot, the relatively rare frequency of these humans in our sample underscores potential differences in loading experienced by the medial and lateral columns of the OH 8 foot compared to modern humans.

Physical activity alters limb bone structure but not entheseal morphology.

Studies of ancient human skeletal remains frequently proceed from the assumption that individuals with robust limb bones and/or rugose, hypertrophic entheses can be inferred to have been highly physically active during life. Here, we experimentally test this assumption by measuring the effects of exercise on limb bone structure and entheseal morphology in turkeys. Growing females were either treated with a treadmill-running regimen for 10 weeks or served as controls. After the experiment, femoral cortical and trabecular bone structure were quantified with µCT in the mid-diaphysis and distal epiphysis, respectively, and entheseal morphology was quantified in the lateral epicondyle. The results indicate that elevated levels of physical activity affect limb bone structure but not entheseal morphology. Specifically, animals subjected to exercise displayed enhanced diaphyseal and trabecular bone architecture relative to controls, but no significant difference was detected between experimental groups in entheseal surface topography. These findings suggest that diaphyseal and trabecular structure are more reliable proxies than entheseal morphology for inferring ancient human physical activity levels from skeletal remains.

Mobility as an emergent property of biological organization: Insights from experimental evolution.

Anthropologists accept that mobility is a critical dimension of human culture, one that links economy, technology, and social relations. Less often acknowledged is that mobility depends on complex and dynamic interactions between multiple levels of our biological organization, including anatomy, physiology, neurobiology, and genetics. Here, we describe a novel experimental approach to examining the biological foundations of mobility, using mice from a long-term artificial selection experiment for high levels of voluntary exercise on wheels. In this experiment, mice from selectively bred lines have evolved to run roughly three times as far per day as those from nonselected control lines. We consider three insights gleaned from this experiment as foundational principles for the study of mobility from the perspective of biological evolution. First, an evolutionary change in mobility will necessarily be associated with alterations in biological traits both directly and indirectly connected to mobility. Second, changing mobility will result in trade-offs and constraints among some of the affected traits. Third, multiple solutions exist to altering mobility, so that various combinations of adjustments to traits linked with mobility can achieve the same overall behavioral outcome. We suggest that anthropological knowledge of variation in human mobility might be improved by greater research attention to its biological dimensions.

Bone shaft bending strength index is unaffected by exercise and unloading in mice.

Anthropologists frequently use the shaft bending strength index to infer the physical activity levels of humans living in the past from their lower limb bone remains. This index is typically calculated as the ratio of bone shaft second moments of area about orthogonal principal axes (i.e. I(max)/I(min)). Individuals with high I(max)/I(min) values are inferred to have been very active, whereas individuals with low values are inferred to have been more sedentary. However, there is little direct evidence that activity has a causal and predictable effect on the shaft bending strength index. Here, we report the results of two experiments that were designed to test the model within which anthropologists commonly interpret the shaft bending strength index. In the first experiment, mice were treated daily with treadmill exercise for 1 month to simulate a high-activity lifestyle. In the second experiment, in an attempt to simulate a low-activity lifestyle, functional weight-bearing was removed from the hindlimbs of mice for 1 month. Femoral mid-shaft structure was determined with µCT. We found that while exercise resulted in significant enhancement of I(max) and I(min) compared with controls, it failed to significantly increase the I(max)/I(min)index. Similarly, stunted bone growth caused by unloading resulted in significantly diminished I(max) and I(min) compared with controls, but low activity did not lead to significantly decreased I(max)/I(min)compared with normal activity. Together, these results suggest that caution is required when the bone shaft bending strength index is used to reconstruct the activity levels of past humans.

Distinct functional roles of primate grasping hands and feet during arboreal quadrupedal locomotion.

It has long been thought that quadrupedal primates successfully occupy arboreal environments, in part, by relying on their grasping feet to control balance and propulsion, which frees their hands to test unstable branches and forage. If this interlimb decoupling of function is real, there should be discernible differences in forelimb versus hind limb musculoskeletal control, specifically in how manual and pedal digital flexor muscles are recruited to grasp during arboreal locomotion. New electromyography data from extrinsic flexor muscles in red ruffed lemurs (Varecia rubra) walking on a simulated arboreal substrate reveal that toe flexors are activated at relatively higher levels and for longer durations than finger flexors during stance phase. This demonstrates that the extremities of primates indeed have different functional roles during arboreal locomotion, with the feet emphasizing maintenance of secure grips. When this dichotomous muscle activity pattern between the forelimbs and hind limbs is coupled with other features of primate quadrupedal locomotion, including greater hind limb weight support and the use of diagonal-sequence footfall patterns, a complex suite of biomechanical characters emerges in primates that allow for the co-option of hands toward non-locomotor roles. Early selection for limb functional differentiation in primates probably aided the evolution of fine manipulation capabilities in the hands of bipedal humans.

Focal enhancement of the skeleton to exercise correlates with responsivity of bone marrow mesenchymal stem cells rather than peak external forces.

Force magnitudes have been suggested to drive the structural response of bone to exercise. As importantly, the degree to which any given bone can adapt to functional challenges may be enabled, or constrained, by regional variation in the capacity of marrow progenitors to differentiate into bone-forming cells. Here, we investigate the relationship between bone adaptation and mesenchymal stem cell (MSC) responsivity in growing mice subject to exercise. First, using a force plate, we show that peak external forces generated by forelimbs during quadrupedal locomotion are significantly higher than hindlimb forces. Second, by subjecting mice to treadmill running and then measuring bone structure with µCT, we show that skeletal effects of exercise are site-specific but not defined by load magnitudes. Specifically, in the forelimb, where external forces generated by running were highest, exercise failed to augment diaphyseal structure in either the humerus or radius, nor did it affect humeral trabecular structure. In contrast, in the ulna, femur and tibia, exercise led to significant enhancements of diaphyseal bone areas and moments of area. Trabecular structure was also enhanced by running in the femur and tibia. Finally, using flow cytometry, we show that marrow-derived MSCs in the femur are more responsive to exercise-induced loads than humeral cells, such that running significantly lowered MSC populations only in the femur. Together, these data suggest that the ability of the progenitor population to differentiate toward osteoblastogenesis may correlate better with bone structural adaptation than peak external forces caused by exercise.

Cross-sectional structural variation relative to midshaft along hominine diaphyses. I. The forelimb.

OBJECTIVES: Analyses of hominine forelimb diaphyseal structure typically employ sections located at midshaft. This study addresses three questions. First, how accurately must midshaft be defined to yield comparable data? Second, does variation in midshaft location due to alternative definitions fall within error ranges such that data gathered using different length measurements are comparable? Third, do error ranges and length metric effects differ between elements or taxa such that certain bones or species are more prone to issues of comparability? MATERIALS AND METHODS: Humeri, radii, and ulnae of Homo, Pan, and Gorilla were CT-scanned at full length and error ranges for three structural parameters (CSA, J, Imax /Imin ) were calculated around midshafts. RESULTS: Distances proximally and distally from midshaft where structural values become significantly different from midshaft values vary between elements, taxa, and structural parameters. Error ranges are largest for the humerus and smallest for the ulna. Among taxa, error ranges for gorillas are largest and those for humans are smallest. Among structural parameters, error ranges depend on element and taxon such that no parameter consistently exhibits larger or smaller error ranges across all bones or species. Variation in midshaft locations originating from different length definitions is small and falls within error ranges defined by maximum length across all elements and taxa. DISCUSSION: Including fragmentary specimens for which midshaft location is uncertain in comparisons of forelimb diaphyseal structure requires evaluation on a case-by-case basis, with consideration to element, taxon, and structural traits of interest. However, midshaft data for all three structural parameters considered here that are recorded using different length measurements can be reasonably compared.

Cross-sectional structural variation relative to midshaft along hominine diaphyses. II. The hind limb.

OBJECTIVES: In comparative analyses of hominine hind limb diaphyseal structure, homologous cross sections are located according to half bone length (midshaft). Here, we address three questions. First, how accurately must midshaft be defined to yield comparable data? Second, does variation in midshaft location due to different ways of measuring length fall within error ranges such that data gathered using different metrics are comparable? Third, do error ranges and length metric effects differ between elements or taxa such that certain bones or species are more prone to issues of comparability? MATERIALS AND METHODS: Femora and tibiae of Homo, Pan, and Gorilla were CT-scanned longitudinally and error ranges for multiple structural parameters (CSA, J, Imax /Imin ) were calculated around midshafts. RESULTS: Distances proximally and distally from midshaft where structural values differ significantly from midshaft values vary between bones, species, and structural traits. Femoral error ranges are typically larger than tibial ranges. In the femur, error ranges are generally largest for chimpanzees and smallest for gorillas. A similar taxonomic pattern is not evident in the tibia. No structural trait consistently displays larger or smaller error ranges across both elements and all species. Variation in midshaft locations stemming from different length definitions is small and falls within observed error ranges defined by any one metric. DISCUSSION: Incorporating fragmentary specimens (e.g., fossils) for which midshaft location is unknown in comparisons of diaphyseal structure necessitates evaluation on a case-by-case basis, with thought to element, taxon, and structural traits of interest. Midshaft data recorded from distinct length measurements are generally comparable.

Variation, sexual dimorphism, and enlargement of the frontal sinus with age in adult South Africans.

OBJECTIVES: To document frontal sinus volume (FSV) in a sample of sub-Saharan Africans with a view to evaluating claims that such populations exhibit comparatively small sinuses. This study also addresses questions related to sexual dimorphism, incidence of sinus aplasia, and the possibility that FSV continues to increase through adulthood. MATERIALS AND METHODS: FSV was measured from CT scans of adult crania from the Dart Collection. Sex and age were known for each individual. Linear cranial dimensions were used to compute a geometric mean from which a scaled FSV was computed for each cranium. RESULTS: FSV does not differ significantly between sexes, but females exhibit a higher incidence of aplasia. There is considerable variation in FSV in this sample, with the average ranking among the higher means reported for other population samples. The incidence of FS aplasia falls within the range of values recorded for other population samples. Although our study is cross-sectional rather than longitudinal, there is strong evidence that FSV continues to increase with age throughout adulthood. DISCUSSION: The FSV mean of our sample contradicts the notion that sub-Saharan Africans possess small sinuses. In a global context, geography (climate and altitude) does not appear to be related to FSV. The absence of sexual dimorphism in our sample is unexpected, as significant dimorphism has been reported for most other population samples. Our results support other indications that the frontal sinus continues to expand throughout adulthood, especially in females, and that it is likely due to bone resorption.

The effects of the industrial transition on lower limb bone structure: A comparison of the inhabitants of Pecos Pueblo and present-day Indigenous peoples of New Mexico.

OBJECTIVES: Comparisons between Indigenous peoples over time and within a particular geographic region can shed light on the impact of environmental transitions on the skeleton, including relative bone strength, sexual dimorphism, and age-related changes. Here we compare long bone structural properties of the inhabitants of the late prehistoric-early historic Pecos Pueblo with those of present-day Indigenous individuals from New Mexico. MATERIALS AND METHODS: Femora and tibiae of 126 adults from Pecos Pueblo and 226 present-day adults were included in the study. Cross-sectional diaphyseal properties-areas and second moments of area-were obtained from past studies of the Pecos Pueblo skeletal sample, and from computed tomography scans of recently deceased individuals in the present-day sample. RESULTS: Femora and tibiae from Pecos individuals are stronger relative to body size than those of present-day Indigenous individuals. Present-day individuals are taller but not wider, and this body shape difference affects cross-sectional shape, more strongly proximally. The tibia shows anteroposterior strengthening among Pecos individuals, especially among males. Sexual dimorphism in midshaft bone shape is stronger within the Pecos Pueblo sample. With aging, Pecos individuals show more medullary expansion but also more subperiosteal expansion than present-day individuals, maintaining bone strength despite cortical thinning. DISCUSSION: Higher activity levels, carried out over rough terrain and throughout adult life, likely explain the relatively stronger lower limb bones of the Pecos individuals, as well as their greater subperiosteal expansion with aging. Greater sexual dimorphism in bone structure among Pecos individuals potentially reflects greater gender-based differences in behavioral patterns.