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.

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.

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.

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.

Microdemographic Determinants of Population Recovery among the Northern Aché.

A pattern of population crash and rapid recovery is a common feature of the pacification and settlement experience of the indigenous peoples of tropical South America. Despite the obvious importance of these events to the demographic and anthropological sciences as a whole, as well as their significant practical implications, little is known about the microdemographic determinants of these paired phenomena. Using methods of asymptotic and stochastic demographic analysis, we reconstructed the microdemographic drivers of this history among one indigenous population: the Northern Aché of eastern Paraguay. This article explores the implications of these relationships for understanding the overall demographic turnaround observed within similar groups, as well as for the future trajectory of the Northern Aché in particular.

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.

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.

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.

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 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.

Cooperative breeding in South American hunter-gatherers.

Evolutionary researchers have recently suggested that pre-modern human societies habitually practised cooperative breeding and that this feature helps explain human prosocial tendencies. Despite circumstantial evidence that post-reproductive females and extra-pair males both provide resources required for successful reproduction by mated pairs, no study has yet provided details about the flow of food resources by different age and sex categories to breeders and offspring, nor documented the ratio of helpers to breeders. Here, we show in two hunter-gatherer societies of South America that each breeding pair with dependent offspring on average obtained help from approximately 1.3 non-reproductive adults. Young married males and unmarried males of all ages were the main food providers, accounting for 93-100% of all excess food production available to breeding pairs and their offspring. Thus, each breeding pair with dependants was provisioned on average by 0.8 adult male helpers. The data provide no support for the hypothesis that post-reproductive females are the main provisioners of younger reproductive-aged kin in hunter-gatherer societies. Demographic and food acquisition data show that most breeding pairs can expect food deficits owing to foraging luck, health disabilities and accumulating dependency ratio of offspring in middle age, and that extra-pair provisioning may be essential to the evolved human life history.

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.

Genetic clues about the origin of Aché hunter-gatherers of Paraguay.

Seventeen genetic studies performed among the until recently hunter-gatherer Aché were reviewed and the corresponding data integrated to general information about this group, and to statistical tests of hypothesis concerning its origin(s). Two features of the Aché gene pool emerge: (a) the distinctiveness in relation to the general pattern of Amerindian genetic data; and (b) the reduced within population genetic variability. As for the origin of this people, the evidence suggests a general Tupian background with considerable introgression of Jê genetic material, which could be explained by the Tupi warfare habit of absorption instead of extermination of defeated individuals.

The beta-globin gene cluster distribution revisited-patterns in Native American populations.

New frequencies for the beta-globin gene cluster haplotypes are presented for the Aché (N = 82 individuals), Guarani (N = 76), and Kaingang (N = 54), three Native South American populations that live in an area between parallels 20 degrees S and 30 degrees S not covered by previous studies at this locus. The haplotype frequencies obtained for the three populations are within the interval observed for 28 other Native American populations. The Aché show much less haplotypes (five) than the other two populations (9-10), the haplotype prevalences being more similar to those of the Guarani than to the Kaingang. The Native American total heterozygosity was about half (0.41) that obtained for the African populations (0.71), but was not much different from those obtained for other continents. A geographical pattern was disclosed in South America by mapping the frequencies of the most common haplotype (haplotype 2), and by means of spatial correlation analysis. The analysis of molecular variance (AMOVA) and pairwise F(ST) data suggest three distinct sectors for the genetic landscape of Native South America: the Andes, the Center/Southeast region, and the Amazon.

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.

Emergence of indigenous vegetation classifications through integration of traditional ecological knowledge and remote sensing analyses.

Traditional ecological knowledge (TEK) can play an important role in the understanding of ecological systems. Although TEK has complemented scientific and managerial programs in a variety of contexts, its formal incorporation into remote sensing exercises has to date been limited. Here, we show that the vegetation classifications of the Ache, an indigenous hunter-gatherer tribe of the Mbaracayu Forest Reserve in Paraguay, are reflected in a supervised classification of satellite imagery of the reserve. Accuracy of classification was toward the low end of the range of published values, but was reasonable given the difficult nature of separating forest classes from satellite images. Comparison of the resultant map with a more traditionally elaborated vegetation map highlights differences between the two approaches and the gain in information obtained by considering TEK classifications. We suggest that integration of TEK and remote sensing may provide alternative insights into the ecology of vegetation communities and land cover, particularly in remote and densely forested areas where ecological field research is often limited by roads and/or trail systems.

Natural selection and molecular evolution in primate PAX9 gene, a major determinant of tooth development.

Large differences in relation to dental size, number, and morphology among and within modern human populations and between modern humans and other primate species have been observed. Molecular studies have demonstrated that tooth development is under strict genetic control, but, the genetic basis of primate tooth variation remains unknown. The PAX9 gene, which codes for a paired domain-containing transcription factor that plays an essential role in the development of mammal dentition, has been associated with selective tooth agenesis in humans and mice, which mainly involves the posterior teeth. To determine whether this gene is polymorphic in humans, we sequenced approximately 2.1 kb of the entire four-exon region (exons 1, 2, 3 and 4; 1,026 bp) and exon-intron (1.1 kb) boundaries of 86 individuals sampled from Asian, European, and Native American populations. We provided evidence that human PAX9 polymorphisms are limited to exon 3 only and furnished details about the distribution of a mutation there in 350 Polish subjects. To investigate the pattern of selective pressure on exon 3, we sequenced ortholog regions of this exon in four species of New World monkeys and one gorilla. In addition, orthologous sequences of PAX9 available in public databases were also analyzed. Although several differences were identified between humans and other species, our findings support the view that strong purifying selection is acting on PAX9. New World and Old World primate lineages may, however, have different degrees of restriction for changes in this DNA region.

Life in the slow lane revisited: ontogenetic separation between chimpanzees and humans.

This study investigates the evolution of human growth by analyzing differences in body mass growth trajectories among three populations: the Ache of eastern Paraguay, the US (NHANES, 1999-2000), and captive chimpanzees. The relative growth statistic "A" from the mammalian growth law is allowed to vary with age and proves useful for comparing growth across different ages, populations, and species. We demonstrate ontogenetic separation between chimpanzees and humans, and show that interspecific differences are robust to variable environmental conditions. The human pattern of slow growth during the lengthened period from weaning to the beginning of the adolescent growth spurt is found among the Ache (low energy availability and high disease load) and also in the US (high energy availability and low disease load). The human growth pattern contrasts with that of the chimpanzee, where absolute growth rates and relative "A" values are faster and less prolonged. We suggest that selection has acted to decrease human growth rates to allow more time for increased cognitive development with lower body-maintenance costs.