Remarkably Low KIR and HLA Diversity in Amerindians Reveals Signatures of Strong Purifying Selection Shaping the Centromeric KIR Region.

The killer-cell immunoglobulin-like receptors (KIR) recognize human leukocyte antigen (HLA) molecules to regulate the cytotoxic and inflammatory responses of natural killer cells. KIR genes are encoded by a rapidly evolving gene family on chromosome 19 and present an unusual variation of presence and absence of genes and high allelic diversity. Although many studies have associated KIR polymorphism with susceptibility to several diseases over the last decades, the high-resolution allele-level haplotypes have only recently started to be described in populations. Here, we use a highly innovative custom next-generation sequencing method that provides a state-of-art characterization of KIR and HLA diversity in 706 individuals from eight unique South American populations: five Amerindian populations from Brazil (three Guarani and two Kaingang); one Amerindian population from Paraguay (Aché); and two urban populations from Southern Brazil (European and Japanese descendants from Curitiba). For the first time, we describe complete high-resolution KIR haplotypes in South American populations, exploring copy number, linkage disequilibrium, and KIR-HLA interactions. We show that all Amerindians analyzed to date exhibit the lowest numbers of KIR-HLA interactions among all described worldwide populations, and that 83-97% of their KIR-HLA interactions rely on a few HLA-C molecules. Using multiple approaches, we found signatures of strong purifying selection on the KIR centromeric region, which codes for the strongest NK cell educator receptors, possibly driven by the limited HLA diversity in these populations. Our study expands the current knowledge of KIR genetic diversity in populations to understand KIR-HLA coevolution and its impact on human health and survival.

Variability of innate immune system genes in Native American populations-relationship with history and epidemiology.

OBJECTIVES: The immune system of a host, defending him/her against invading pathogens, has two main subsystems: innate immunity and acquired immunity. There are several evidences showing that Native American populations are immunologically different from non-Native populations. Our aim was to describe the variability of innate immune system genes in Native American populations. MATERIALS AND METHODS: We investigated heterozygozities and patterns of population differentiation (FST ) of 14 polymorphisms related to the innate immune response in five Native American populations (Aché, Guarani-Kaiowá, Guarani-Ñandeva, Kaingang, and Xavante) and the results were compared with the three major world population data (YRI, CEU, and CHB) available at the 1,000 genomes database. RESULTS: Mean heterozygosities ranged between 0.241 ± 0.057 (Aché) and 0.343 ± 0.033 (Kaingang), but no significant differences were observed (Friedman test, P = 0.197). Mean heterozygosities were also not significantly different when Amerindians were pooled and compared with the 1000 genomes populations (Friedman test, P = 0.506). When the Native American populations were grouped as Amerindians, a significantly higher FST value (0.194) was observed between the Amerindian and African populations. The Ewens-Watterson neutrality test showed that these markers are not under strong selective pressure. DISCUSSION: Native American populations present similar levels of heterozygosity as those of other continents, but are different from Africans in the frequency of polymorphisms of innate immune genes. This higher differentiation is probably due to demographic processes that occurred during the out-of-Africa event.

Diurnal variation in salivary cortisol across age classes in Ache Amerindian males of Paraguay.

OBJECTIVES: Cortisol levels exhibit a diurnal rhythm in healthy men, with peaks in the morning and troughs in the evening. Throughout age, however, this rhythm tends to flatten. This diurnal flattening has been demonstrated in a majority of industrialized populations, although the results have not been unanimous. Regardless, little attention has been paid to nonindustrialized, foraging populations such as the Ache Amerindians of Paraguay. As testosterone levels had previously been shown to diminish with age in this population (Bribiescas and Hill [2010]: Am J Hum Biol 22: 216-220), we hypothesized that cortisol levels would behave similarly, flattening in rhythmicity over age. METHODS: We examined morning and evening salivary cortisol samples in Ache Amerindian men in association with age (n = 40, age range 20-64 years). RESULTS: Men in the first age class (<20-29 years) exhibited significantly different morning (AM) and evening (PM) values as did men in the second age class (30-39 years). However, men in the third and fourth age classes (40-49 years, and >50 years, respectively) did not exhibit a significant difference between AM and PM values. CONCLUSION: Ache Amerindian men exhibit a flattening of the diurnal rhythm across age classes. Our results were able to capture both within- and between-individual variations in cortisol levels, and reflected age-related contrasts in daily cortisol fluctuations. The flattening of the diurnal rhythm with age among the Ache may reflect a common and shared aspect of male senescence across ecological contexts and lifestyles. Am. J. Hum. Biol. 27:344-348, 2015. © 2014 Wiley Periodicals, Inc.

Fitness consequences of spousal relatedness in 46 small-scale societies.

Social norms that regulate reproductive and marital decisions generate impressive cross-cultural variation in the prevalence of kin marriages. In some societies, marriages among kin are the norm and this inbreeding creates intensive kinship networks concentrated within communities. In others, especially forager societies, most marriages are between more genealogically and geographically distant individuals, which generates a larger number of kin and affines of lesser relatedness in more extensive kinship networks spread out over multiple communities. Here, we investigate the fitness consequence of kin marriages across a sample of 46 small-scale societies (12,439 marriages). Results show that some non-forager societies (including horticulturalists, agriculturalists and pastoralists), but not foragers, have intensive kinship societies where fitness outcomes (measured as the number of surviving children in genealogies) peak at commonly high levels of spousal relatedness. By contrast, the extensive kinship systems of foragers have worse fitness outcomes at high levels of spousal relatedness. Overall, societies with greater levels of inbreeding showed a more positive relationship between fitness and spousal relatedness.

Evolutionary history of partible paternity in lowland South America.

Partible paternity, the conception belief that more than one man can contribute to the formation of a fetus, is common in lowland South America and characterized by nonexclusive mating relationships and various institutionalized forms of recognition and investment by multiple cofathers. Previous work has emphasized the fitness benefits for women where partible paternity beliefs facilitate paternal investment from multiple men and may reduce the risk of infanticide. In this comparative study of 128 lowland South American societies, the prevalence of partible paternity beliefs may be as much as two times as common as biologically correct beliefs in singular paternity. Partible paternity beliefs are nearly ubiquitous in four large language families--Carib, Pano, Tupi, and Macro-Je. Phylogenetic reconstruction suggests that partible paternity evolved deep in Amazonian prehistory at the root of a tentative Je-Carib-Tupi clade. Partible paternity often occurs with uxorilocal postmarital residence (males transfer), although there are exceptions. Partible paternity may have benefits for both sexes, especially in societies where essentially all offspring are said to have multiple fathers. Despite a decrease in paternity certainty, at least some men probably benefit (or mitigate costs) by increasing their number of extramarital partners, using sexual access to their wives to formalize male alliances, and/or sharing paternity with close kin.

Circadian variation in salivary testosterone across age classes in Ache Amerindian males of Paraguay.

Testosterone levels exhibit a circadian rhythm in healthy men, with morning levels tending to be higher compared to evening titers. However, circadian rhythms wane with age. Although this has been described in males living within industrialized settings, age-related changes have not received similar attention in populations outside these contexts. Because many nonindustrialized populations, such as Ache Amerindians of Paraguay, exhibit testosterone levels that are lower than what is commonly reported in the clinical literature and lack age-associated variation in testosterone, it was hypothesized that Ache men would not show age-related variation in testosterone circadian rhythms. Diurnal rhythmicity in testosterone within and between Ache men in association with age (n = 52; age range, 18-64) was therefore examined. A significant negative association was evident between the ratio of morning and evening salivary testosterone and age (r = -0.28, P = 0.04). Men in their third decade of life exhibited significant diurnal variation (P = 0.0003), whereas older and younger age classes did not. Men between the ages of 30 and 39 also exhibited a higher AM:PM testosterone ratio compared to 40-49 and 50< year old men (P = 0.002, 0.006). Overall, declines in testosterone with aging may not be universal among human males, however, within-individual analyses of diurnal variation capture age-related contrasts in daily testosterone fluctuations. Circadian rhythmicity differs with age among the Ache and may be a common aspect of reproductive senescence among men regardless of ecological context.

Developmental plasticity in fat patterning of Ache children in response to variation in interbirth intervals: a preliminary test of the roles of external environment and maternal reproductive strategies.

A firm link between small size at birth and later more centralized fat patterning has been established in previous research. Relationships between shortened interbirth intervals and small size at birth suggest that maternal energetic prioritization may be an important, but unexplored determinant of offspring fat patterning. Potential adaptive advantages to centralized fat storage (Baker et al., 2008: In: Trevathan W, McKenna J, Smith EO, editors. Evolutionary Medicine and Health: New Perspectives. New York: Oxford) suggest that relationships with interbirth intervals may reflect adaptive responses to variation in patterns of maternal reproductive effort. Kuzawa (2005: Am J Hum Biol 17:5-21; 2008: In: Trevathan W, McKenna J, Smith EO, editors. Evolutionary Medicine and Health: New Perspectives. New York: Oxford) has argued that maternal mediation of the energetic quality of the environment is a necessary component of developmental plasticity models invoking predictive adaptive responses (Gluckman and Hanson 2004: Trends Endocrinol Metab 15:183-187). This study tested the general hypothesis that shortened interbirth intervals would predict more centralized fat patterning in offspring. If long-term maternally mediated signals are important determinants of offspring responses, then we expected to observe a relationship between the average interbirth interval of mothers and offspring adiposity, with no relationship with the preceding interval. Such a finding would suggest that maternal, endogenous resource allocation decisions are related to offspring physiology in a manner consistent with Kuzawa's description. We observed exactly such a relationship among the Ache of Paraguay, suggesting that maternally mediated in utero signals of postnatal environments may be important determinants of later physiology. The implications of these findings are reviewed in light of life history and developmental plasticity theories and ourability to generalize the results to other populations. Recommendations for further empirical research are briefly summarized.

Vitamin D receptor gene polymorphisms and susceptibility M. tuberculosis in native Paraguayans.

Tuberculosis (TB) is a significant health problem for most of the world's populations, and prevalence among indigenous groups is typically higher than among their nonindigenous neighbors. Native South Americans experience high rates of TB, but while research in several other world populations indicates that susceptibility is multifactorial, polygenic, and population-specific, little work has been undertaken to investigate factors involved in Native American susceptibility. We conducted a family-based association study to examine immunologically relevant polymorphisms of a candidate gene, the vitamin D receptor, in conjunction with three measures of TB status in two Native Paraguayan populations, the Aché and the Avá. This is the first large-scale genetic analysis of Native South Americans to examine susceptibility to both infection and disease following exposure to M. tuberculosis. These two types of susceptibility reflect differences in innate and acquired immunity that have proven difficult to elucidate in other populations. Our results indicate that among the Aché, the FokI F allele protects individuals from infection, while the TaqI t allele protects against active disease but not infection. In particular, FF homozygotes are 17 times more likely to test positive for exposure to TB, but no more likely to have ever been diagnosed with active TB. TT individuals are 42 times less likely to mount a delayed-type hypersensitivity response, and the T allele was significantly more likely to have been transmitted to offspring who have been diagnosed with active TB. This ongoing research is of vital importance to indigenous groups of the Americas, because if there is a population-specific component to TB susceptibility, it will likely prove most effective to incorporate this into future treatment and prevention strategies.

The public health implications of maternal care trade-offs.

The socioeconomic and ethnic characteristics of parents are some of the most important correlates of adverse health outcomes in childhood. However, the relationships between ethnic, economic, and behavioral factors and the health outcomes responsible for this pervasive finding have not been specified in child health epidemiology. The general objective of this paper is to propose a theoretical approach to the study of maternal behaviors and child health in diverse ethnic and socioeconomic environments. The specific aims are: (a) to describe a causal pathway between the utility that women obtain through work outside the home and through child care and disease hazard rates in childhood using an optimization model; (b) to specify the influence of ethnic and socioeconomic factors on model constraints; (c) to use the model as a tool to learn about how different combinations of maternal wage labor and child care time might influence child health outcomes in diverse social contexts; (d) to identify parameters that will require measurement in future research; (e) to discuss research strategies that will enable us to obtain these measurements; and (f) to discuss the implications of the model for biostatistical modeling and public health intervention. Optimization models are powerful heuristic tools for understanding how ethnic, environmental, family, and personal characteristics can place important constraints on both the quality and quantity of care that women can provide to their children. They provide a quantitative appreciation for the difficult trade-offs that most women face between working in order to purchase basic goods that children cannot do without (e.g., food, clothing, shelter, health insurance), and increasing offspring well-being through child care (e.g., training in social skills, affection, protection from environmental hazards, help with homework).

Are Isolated Indigenous Populations Headed toward Extinction?

At least 50 indigenous groups spread across lowland South America remain isolated and have only intermittent and mostly hostile interactions with the outside world. Except in emergency situations, the current policy of governments in Brazil, Colombia, and Peru towards isolated tribes is a "leave them alone" strategy, in which isolated groups are left uncontacted. However, these no-contact policies are based on the assumption that isolated populations are healthy and capable of persisting in the face of mounting external threats, and that they can maintain population viability in the long-term. Here, we test this assumption by tracking the sizes and movements of cleared horticultural areas made by 8 isolated groups over the last 10-14 years. We used deforestation data derived from remote sensing Landsat satellite sensors to identify clearings, and those were then validated and assessed with high-resolution imagery. We found only a single example of a relatively large and growing population (c. 50 cleared ha and 400 people), whereas all of the other 7 groups exhibited much smaller villages and gardens with no sizable growth through time. These results indicated that the smaller groups are critically endangered, and it prompts an urgent re-thinking of policies toward isolated populations, including plans for well-organized contacts that may help save lives and rescue isolated indigenous populations from imminent extinction.

The role of variants from the innate immune system genes in tuberculosis and skin test response in a Native American population.

Native American populations show higher tuberculosis (TB) mortality and infectivity rates than non-Native populations. Variants in the innate immune system seem to have an important role on TB susceptibility. The role of some innate immune system variants in TB susceptibility and/or skin test response (PPD) were investigated in the Aché, a Native American population. Complement receptor 1 and toll like receptor 9 variants were associated with anergy to PPD and protection to TB, respectively. These findings demonstrate an important role of the innate immune system variants in TB susceptibility.

Mortality from contact-related epidemics among indigenous populations in Greater Amazonia.

European expansion and contact with indigenous populations led to catastrophic depopulation primarily through the introduction of novel infectious diseases to which native peoples had limited exposure and immunity. In the Amazon Basin such contacts continue to occur with more than 50 isolated indigenous societies likely to make further contacts with the outside world in the near future. Ethnohistorical accounts are useful for quantifying trends in the severity and frequency of epidemics through time and may provide insight into the likely demographic consequences of future contacts. Here we compile information for 117 epidemics that affected 59 different indigenous societies in Greater Amazonia and caused over 11,000 deaths between 1875 and 2008, mostly (75%) from measles, influenza, and malaria. Results show that mortality rates from epidemics decline exponentially through time and, independently, with time since peaceful contact. The frequency of documented epidemics also decreases with time since contact. While previous work on virgin soil epidemics generally emphasizes the calamity of contacts, we focus instead on improvements through time. The prospects for better survivorship during future contacts are good provided modern health care procedures are implemented immediately.

Causes, consequences, and kin bias of human group fissions.

Fissions of human communities are monumental occasions with consequences for cultural and genetic variation and divergence through time by means of serial founder effects. An ethnographic review shows that most human group fissions are fueled primarily by internal political conflict and secondarily by resource scarcity. As found for other social animals, human fissions lead to subgroups that have higher levels of relatedness as compared with the original community because of kin-biased assortment known as the lineal effect. Fission processes that increase the average relatedness of subgroups are important because relatedness governs how strongly kin/group selection favors social behaviors such as warfare, peacekeeping, and other forms of collection action. However, random individual assortment is not an appropriate null model for evaluating lineage assortment because nuclear families and extended households are expected to remain together, which in and of itself forces higher relatedness in smaller subgroups. We develop a lineage assortment index where low values represent subgroups with coefficients of relatedness near those expected if nuclear and extended households had chosen to associate into random groupings. Two fissions of Ache villages (Paraguay) are examples of this type of fission with a low lineage assortment index not significantly different from zero as evaluated with controlled simulations. On the other extreme, a lineage assortment index near unity represents a lineal fission that maximizes the relatedness of subgroups such as the perfect split of a lineage into sublineages. A fission of Piaroa (Venezuela) fits this scenario. While previous discussions of fission have emphasized similarities among human studies and even other social mammals, we highlight the full range of potential kin bias in the formation of new communities.

Hunter-gatherer inter-band interaction rates: implications for cumulative culture.

Our species exhibits spectacular success due to cumulative culture. While cognitive evolution of social learning mechanisms may be partially responsible for adaptive human culture, features of early human social structure may also play a role by increasing the number potential models from which to learn innovations. We present interview data on interactions between same-sex adult dyads of Ache and Hadza hunter-gatherers living in multiple distinct residential bands (20 Ache bands; 42 Hadza bands; 1201 dyads) throughout a tribal home range. Results show high probabilities (5%-29% per year) of cultural and cooperative interactions between randomly chosen adults. Multiple regression suggests that ritual relationships increase interaction rates more than kinship, and that affinal kin interact more often than dyads with no relationship. These may be important features of human sociality. Finally, yearly interaction rates along with survival data allow us to estimate expected lifetime partners for a variety of social activities, and compare those to chimpanzees. Hadza and Ache men are estimated to observe over 300 men making tools in a lifetime, whereas male chimpanzees interact with only about 20 other males in a lifetime. High intergroup interaction rates in ancestral humans may have promoted the evolution of cumulative culture.

Heritability and fitness correlates of personality in the Ache, a natural-fertility population in Paraguay.

The current study assessed the heritability of personality in a traditional natural-fertility population, the Ache of eastern Paraguay. Self-reports (n = 110) and other-reports (n = 66) on the commonly used Big Five Personality Inventory (i.e., extraversion, agreeableness, conscientiousness, neuroticism, openness) were collected. Self-reports did not support the Five Factor Model developed with Western samples, and did not correlate with other-reports for three of the five measured personality factors. Heritability was assessed using factors that were consistent across self- and other-reports and factors assessed using other-reports that showed reliabilities similar to those found in Western samples. Analyses of these items in combination with a multi-generation pedigree (n = 2,132) revealed heritability estimates similar to those found in most Western samples, although we were not able to separately estimate the influence of the common environment on these traits. We also assessed relations between personality and reproductive success (RS), allowing for a test of several mechanisms that might be maintaining heritable variation in personality. Phenotypic analyses, based largely on other-reports, revealed that extraverted men had higher RS than other men, but no other dimensions of personality predicted RS in either sex. Mothers with more agreeable children had more children, and parents mated assortatively on personality. Of the evolutionary processes proposed to maintain variation in personality, assortative mating, selective neutrality, and temporal variation in selection pressures received the most support. However, the current study does not rule out other processes affecting the evolution and maintenance of individual differences in human personality.

Evolutionary history of hunter-gatherer marriage practices.

BACKGROUND: The universality of marriage in human societies around the world suggests a deep evolutionary history of institutionalized pair-bonding that stems back at least to early modern humans. However, marriage practices vary considerably from culture to culture, ranging from strict prescriptions and arranged marriages in some societies to mostly unregulated courtship in others, presence to absence of brideservice and brideprice, and polyandrous to polygynous unions. The ancestral state of early human marriage is not well known given the lack of conclusive archaeological evidence. METHODOLOGY: Comparative phylogenetic analyses using data from contemporary hunter-gatherers around the world may allow for the reconstruction of ancestral human cultural traits. We attempt to reconstruct ancestral marriage practices using hunter-gatherer phylogenies based on mitochondrial DNA sequences. RESULTS: Arranged marriages are inferred to go back at least to first modern human migrations out of Africa. Reconstructions are equivocal on whether or not earlier human marriages were arranged because several African hunter-gatherers have courtship marriages. Phylogenetic reconstructions suggest that marriages in early ancestral human societies probably had low levels of polygyny (low reproductive skew) and reciprocal exchanges between the families of marital partners (i.e., brideservice or brideprice). DISCUSSION: Phylogenetic results suggest a deep history of regulated exchange of mates and resources among lineages that enhanced the complexity of human meta-group social structure with coalitions and alliances spanning across multiple residential communities.

Co-residence patterns in hunter-gatherer societies show unique human social structure.

Contemporary humans exhibit spectacular biological success derived from cumulative culture and cooperation. The origins of these traits may be related to our ancestral group structure. Because humans lived as foragers for 95% of our species' history, we analyzed co-residence patterns among 32 present-day foraging societies (total n = 5067 individuals, mean experienced band size = 28.2 adults). We found that hunter-gatherers display a unique social structure where (i) either sex may disperse or remain in their natal group, (ii) adult brothers and sisters often co-reside, and (iii) most individuals in residential groups are genetically unrelated. These patterns produce large interaction networks of unrelated adults and suggest that inclusive fitness cannot explain extensive cooperation in hunter-gatherer bands. However, large social networks may help to explain why humans evolved capacities for social learning that resulted in cumulative culture.

Longitudinal study of tuberculosis outcomes among immunologically naive Aché natives of Paraguay.

This study documents the course of a tuberculosis epidemic in an immunologically naive group of South American Indians within fewer than 20 years after first sustained contact with outsiders. Groups of Northern Aché (ah-CHAY) of eastern Paraguay were contacted and settled on reservations between 1971-1979. Not surprisingly, the Aché are very susceptible to tuberculosis, and the epidemiological characteristics of the disease are quite different from those of populations that have had tuberculosis for centuries. Within 6 years of the first detected case of tuberculosis among the Aché, the prevalence rate of active tuberculosis cases reached 18.2%, and of infected cases among adults, 64.6%, some of the highest rates ever reported for any human group. Remarkably, males and females are equally likely to have been diagnosed with active tuberculosis, Aché children between birth and 5 years of age are least vulnerable to tuberculosis, high nutritional and socioeconomic status do not decrease the risk of disease or infection, and children immunized with BCG are less responsive to tuberculin challenge than are other children. Moreover, similar to the Yanomamö, but unlike populations of European or African descent, a high percentage of Aché with active disease test negative on tuberculin challenge tests (purified protein derivative; PPD). These differences may be due to a high prevalence of diminished cell-mediated immunity, and T-helper 2 dominance. We also hypothesize that these immunological characteristics, low genetic diversity, hostile intergroup interactions, and behavioral noncompliance to treatment protocols together contribute to the high rates of active disease observed. Existing tuberculosis control programs are poorly equipped to handle the impact of these causal complexities on the course of recent tuberculosis epidemics that have quickly spread throughout native communities of Latin America during the last decade.