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N-acetyltransferase 2 (NAT2) is responsible for metabolizing xenobiotics; NAT2 polymorphisms lead to three phenotypes: rapid, intermediate and slow acetylators. We aimed to investigate NAT2 diversity in Native Americans. NAT2 exon 2 was sequenced for 286 individuals from 21 populations (Native American and American Mestizos). Excluding the basal/rapid haplotype NAT2*4, the most frequent haplotypes are NAT2*5B (35.95%) in hunter-gatherers and NAT2*7B (20.61%) and NAT2*5B (19.08%) in agriculturalists that were related to the slow phenotype. A new haplotype was identified in two Amerindians. Data from the ~44 kb region surrounding NAT2 in 819 individuals from Africa, East-Asia, Europe and America were used in additional analyses. No significant differences in the acetylator NAT2 haplotype and phenotype distributions were found between Native American populations practicing farming and/or herding and those practicing hunting and gathering, probably because of the absence or weakness of selection pressures and presence of demographic and random processes preventing detection of any selection signal.

N-acetyltransferase 2 (NAT2), an important enzyme in clinical pharmacology, metabolizes antibiotics such as isoniazid and sulfamethoxazole, and catalyzes the transformation of aromatic and heterocyclic amines from the environment and diet into carcinogenic intermediates. Polymorphisms in NAT2 account for variability in the acetylator phenotype and the pharmacokinetics of metabolized drugs. Native Americans, settled in rural areas and large cities of Latin America, are under-represented in pharmacogenetics studies; therefore, we sequenced the coding region of NAT2 in 456 chromosomes from 13 populations from the Americas, and two from Siberia, detecting nine substitutions and 11 haplotypes. Variants *4 (37%), *5B (23%) and *7B (24%) showed high frequencies. Average frequencies of fast, intermediate and slow acetylators across Native Americans were 18, 56 and 25%, respectively. NAT2 intra-population genetic diversity for Native Americans is higher than East Asians and similar to the rest of the world, and NAT2 variants are homogeneously distributed across native populations of the continent.

A total of 1558 base pairs in the 16p13.3 region were investigated in 98 individuals of Mongolian, Northern Arctic and Amerindian affiliation, and the results compared with those obtained in a previous worldwide study of the same genomic region. Fifty-five polymorphic sites could be classified into thirty-five haplotypes from the total data. A median joining network based on the haplotypes revealed two distinct clusters: one with low diversity, with haplotypes found in all five geographic-ethnic categories; while the other, with the most divergent haplotypes, was composed mainly of Africans and a few Amerindians. Almost all neutrality parameters yielded significantly negative values. Demographic simulations with the exclusively Amerindian dataset rejected all scenarios, including a bottleneck beginning more than 12,000 years ago. The demographic scenarios tested considering population growth were similar among the Amerindian and worldwide or Eurasian data sets. The results suggest that Amerindians are a representative sample of Eurasian populations, preserving the signal of demographic growth from the out of Africa exodus and, together with data from uniparental markers, support a scenario of a bottleneck of moderate intensity during the peopling of the New World.

The low density lipoprotein receptor gene (LDLR) contains many Alu insertions, and is especially Alu-rich at its 3'-untranslated region (3'-UTR). Previous studies suggested that the LDLR 3'-UTR could regulate gene expression by the stabilization of its mRNA. Given the faster Alu evolutionary rate, and wondering about its consequences in a possibly regulatory locus, we have studied approximately 800 bp of 222 chromosomes from individuals of African, Asian, Caucasian and Amerind ancestry, to better understand the evolution of the worldwide genetic diversity at this locus. Twenty-one polymorphic sites, distributed in 15 haplotypes, were found. High genetic diversity was observed, concentrated in one Alu insertion (Alu U), which also shows a fast evolutionary rate. Genetic diversity is similar in all populations except Amerinds, suggesting a bottleneck during the peopling of the American continent. Three haplotype clusters (A, B, C) are distinguished, cluster A being the most recently formed (approximately 500,000 years ago). No clear geographic structure emerges from the haplotype network, the global F(st) (0.079) being lower than the average for the human genome. When ancestral population growth is taken into account, neutrality statistics are higher than expected, possibly suggesting the action of balancing selection worldwide.

One-hundred three individuals from two Mongolian, two Siberian, and ten native American populations were studied in relation to a 340-bp sequence from an Alu insertion located in the 3' untranslated region of the LDLR gene. Seven haplotypes have been determined, and haplotype B1 was the most common, accounting for about half the sequences found. In general, diversity values are quite high, about 2.5 times higher than those found in other autosomal Alu sequences. Almost all (93%) of the variability occurs at the intrapopulation level, but the greatest among-group differentiation (6-8%) was found when we grouped in a single population all Native Americans plus Siberian Eskimos and Chukchi and compared them with Mongolians. This result is compatible with earlier mtDNA and Y-chromosome suggestions of a single origin for the first colonizers of the American continent. With this nuclear locus it was not possible to broadly distinguish between Central and South American natives. No evidence of selection or marked demographic changes was obtained with these data.

A total of 100 chickens from the Brazilian (blue-egg Caipira) native breed were studied in relation to exon 2 of the B-F genes of the major histocompatibility complex (MHC) region. After a first screening on 100 birds, 22 animals were selected for amplification, cloning and sequencing experiments of exons 2-4 (a total of 1048 bp) of their DNA. Twenty-three sequences were obtained, of which at least 10 appear novel. Inferred protein sequences were compared with those previously described, totalling 41 different sequences with amino acid changes in 33 of the 88 sites in alpha1, and 34 of the 91 sites in alpha2 domains. Allele expression was investigated in these animals through cloning experiments. The blue-egg Caipira chickens may provide a source of novel B-F alleles for genetic improvement programmes.

A total of 91 Ayoreo individuals previously studied for blood groups and protein markers, living in two Bolivian and one Paraguayan communities, were extensively investigated in relation to the hypervariable 1 segment of the control and eight coding regions of their mitochondrial DNA (mtDNA). They show an extremely reduced mtDNA variability, the observed haplotypes being classifiable in just two haplogroups (C and D). They were also variously studied in relation to six Alu insertions; in this case, however, the prevalences found did not depart markedly from those obtained in other populations of this ethnic group. To assess the Ayoreo position in relation to these populations, 11 other groups that had also been studied for these systems and for blood groups and proteins were selected. The dendrograms obtained with two of the three sets of markers showed distinct patterns, but the Ayoreo were placed in a central position in both the blood group + proteins and Alu insertions trees. Therefore, they are clearly distinct in relation to their mtDNA only, suggesting a strong founder effect and/or random loss of variability in this system.

The study of the HLA variability of Native American populations revealed several alleles specific to one or more of the Latin American indigenous populations. The analysis of Amerindian groups distributed all over the continent might inform about the area of origin and the dispersal of these alleles and shed light on the evolution of this remarkable polymorphism. Moreover, HLA alleles and haplotypes are excellent markers to understand the genetic relationships between populations. For these reasons, we characterized the HLA class II polymorphism in seven South American Amerindian populations and compared the results with those previously reported for other Amerindian groups. The Guarani-Kaiowá (n = 160) and Guarani-Nandeva (n = 87) were from the Brazilian state of Mato Grosso do Sul, the Guarani-M'byá (n = 93) and Kaingang (n = 235) from Paraná state, the Aché (n = 89) from eastern Paraguay, the Quechua (n = 44) from Andean Peru. From Amazonia, a heterogeneous group was analyzed (n = 45). The most frequent alleles and haplotypes are common also in other Amerindian populations. Each HLA-DRB1 allele was typically found in combination with just one DQA1-DQB1 haplotype, most likely as a result of some form of random genetic drift and reduced gene flow from non-Amerindians. The frequency distribution differed significantly among all populations, although differences were less pronounced between the Guarani subgroups. Marker alleles allowed an estimate of European and sub-Saharan African gene flow into these populations: Quechua 23%, Guarani-Nandeva 14%, Kaingang 7%, Guarani-M'byá 4%, Guarani-Kaiowá, Amazonia, and Aché 0%. Interestingly, the DRB1*1413 allele, previously found only among the Guarani-M'byá (frequency 15%), appeared in the Aché (8%). The relationship of the Aché to other Amerindian populations is unclear, and this finding reveals a link with the Guarani. On the basis of genetic distance and the HLA allele/haplotype set, we propose that the Aché are differentiated Tupi-Guarani group, most closely related to the Guarani-M'byá.

To better understand the relationship between genetic variability, geographical distance, and linguistic affiliation in South Amerinds, and to elucidate whether the migration rate is the same for both sexes, spatial autocorrelation, Mantel's test, and F(ST) analyses were performed in four sets of populations and alleles (group 1: 48 populations, 12 alleles; group 2: 16 (all belonging to the Tupi linguistic group) and 12; group 3: 21 and 17; and group 4: 28 and 4 haplotypes). Groups 1-3 included blood group and protein (i.e., serum protein, red cell enzymes, and immunoglobulin systems), while group 4 was concerned with mitochondrial DNA (mtDNA) only. The latter set was also subjected to a molecular analysis of variance (AMOVA) evaluation. The frequencies of statistically significant correlograms were lower than those obtained in other populations when the blood groups and protein systems were considered, but 3 of the 4 mtDNA haplogroups gave suggestions of population structure. The variability in this organelle is also significantly correlated with language when geography is held constant. Migration per generation is generally low, but higher estimates were obtained for females. The AMOVA results suggest that populations whose members speak the same language are genetically homogeneous and may be viewed as the ultimate evolutionary unit at this level of analysis., (Copyright 2002 Wiley-Liss, Inc.)

New data on 17 blood group and protein genetic systems obtained among the Ayoreo and Lengua Indians of Paraguay are presented. They include the first report on the red cell band-3 protein investigated among South American Indians. This information was integrated with previous results available for these two and four other groups. Five of the six populations reside in the Chaco area, while the sixth was included as an outgroup living elsewhere in Paraguay. Four of the five Chaco tribes exhibit good genetic homogeneity, but the Ayoreo are somewhat different. The results confirm the Chaco as a distinct biological (as well as cultural and economic) region, which should be considered in evaluations of genetic variability among South American Indians.

To evaluate the genetic diversity of Brazilian populations and contribute to the knowledge of their evolutionary history this study investigated three TP53 polymorphisms (BstUI and MspI RFLPs in exon 4 and intron 6, respectively, and a 16 bp duplication in intron 3). The populations studied were: 114 Amerindians from five Brazilian Indian tribes (Gavião, Surui, Zoró, Wai-Wai and Xavante), 95 Euro-Brazilians and 70 Afro-Brazilians. The polymorphisms were all analysed using PCR amplifications. Gene frequencies and haplotype prevalences were calculated using the ARLEQUIN software. The genetic affinities of these groups with other world populations were estimated by the D(A) distance and neighbour joining method, using the NJBAFD computer program. Neo-Brazilians (immigrants from Europe and Africa) generally presented more variability than Amerindians, Afro-Brazilians being the most variable population. Among Amerindians, Gavião is the only group polymorphic for the three markers. Wai-Wai showed variability in BstUI and MspI RFLPs, while the other tribes were monomorphic for the 16 bp A1 and MspI A2 alleles. A rare haplotype (1-2-1) was verified among the Wai-Wai. This haplotype was previously described in a Chinese sample only, but with low frequency. Therefore, either this combination was lost in the other tribes by genetic drift, recombination, or other factor, or it occurs in the Wai-Wai and Chinese by independent events. The Gavião also presented a haplotype (2-1-1) not observed in the other Amerindians; but since it is present in Euro- and Afro-Brazilians. its occurrence there is probably due to interethnic admixture. The relationships of several world populations obtained using TP53 indicates that this marker is very efficient in clustering populations of the same ethnic group.

Two microsatellites (CD4 and F13A1) were investigated in seven Brazilian populations: one group each of European- and African-derived subjects from Porto Alegre, southern Brazil, and five Amerindian tribes (three Tupi-Mondé speaking [Gavião, Surui, and Zoró], one Macro-Gê [Xavante], and one Carib [Wai-Wai]). For both markers, neo-Brazilians presented with a high diversity, but Amerindians showed a low level of variability. Genotype frequency distributions were heterogeneous among populations, the only exception being similar CD4 frequencies in Afro- and Euro-Brazilians. Gene diversity analysis revealed that most of the total variation is due to intrapopulational diversity in all populations. Because of the high information content of these markers in Afro- and Euro-Brazilians, these systems are most appropriate for forensic analyses. The comparison among Brazilian and other world populations revealed high similarity among populations of the same ethnic group, indicating a high discriminative power for these markers.

Selected aspects of the evolutionary process and more specifically of the genetic variation are considered, with an emphasis in studies performed by my group. One key aspect of evolution seems to be the concomitant occurrence of dichotomic, contradictory (dialect) processes. Genetic variation is structured, and the dynamics of change at one level is not necessarily paralleled by that in another. The pathogenesis-related protein superfamily can be cited as an example in which permanence (the maintenance of certain key genetic features) coexists with change (modifications that led to different functions in different classes of organisms). Relationships between structure and function are exemplified by studies with hemoglobin Porto Alegre. The genetic structure of tribal populations may differ in important aspects from that of industrialized societies. Evolutionary histories also may differ when considered through the investigation of patrilineal or matrilineal lineages. Global evaluations taking into consideration all of these aspects are needed if we really want to understand the meaning of genetic variation.

We report the distribution of the APOB signal peptide polymorphism in 5 native populations of South America: 2 samples of Mataco and 1 sample each of Pilagá and Toba from the Argentinian Chaco and 1 sample of Ache from the Paraguay forest. A randomly selected subsample of a previously studied sample from the Cayapa of Ecuador (Scacchi et al. 1997) was reanalyzed to investigate probable differences attributable to sampling, laboratory techniques, or interobserver error. The polymorphism observed in the signal peptide region of the APOB gene among native populations of South America exhibits the same range of variation found among geographic continental populations, confirming the high genetic heterogeneity of South Amerindians. Extremes in the allele prevalences were found among the Mataco and Ache, populations not far apart geographically. The small differences in genotype and allele frequencies between the subsample of the Cayapa analyzed here and the original Cayapa sample and between the 2 Mataco samples were not statistically significant and most likely were due to sampling error.

A total of 582 individuals (1,164 chromosomes) from two African, eight African-derived South American, five South American Amerindian, and three Brazilian urban populations were studied at four variable number of tandem repeat (VNTR) and two short tandem repeat (STR) hypervariable loci. These two sets of loci did not show distinct allele profiles, which might be expected if different processes promoted their molecular differentiation. The two African groups showed little difference between them, and their intrapopulational variation was similar to those obtained in the African-derived South American communities. The latter showed different degrees of interpopulation variability, despite the fact that they presented almost identical average degrees of non-African admixture. The F(ST) single locus estimates differed in the five sets of populations, probably due to genetic drift, indicating the need to consider population structure in the evaluation of their total variability. A high interpopulational diversity was found among Amerindian populations in relation to Brazilian African-derived isolated communities. This is probably a consequence of the differences in the patterns of gene flow and genetic drift that each of these semi-isolated groups experienced., (Copyright 1999 Wiley-Liss, Inc.)

Three apolipoprotein B restriction fragment length polymorphism (RFLPs) (XbaI, MspI, and EcoRI) and the signal peptide insertion-deletion polymorphism were investigated using the polymerase chain reaction in 140 individuals from 5 Brazilian Indian tribes. All studied markers were polymorphic in this ethnic group. The insertion allele 5' beta SP*29 at the signal peptide previously observed in Mexican Americans was detected in about 8% of the chromosomes of 2 tribes (Gavião and Zoró), therefore confirming the Amerindian origin of this allele. Negative linkage disequilibrium was observed between alleles at the signal peptide and the EcoRI polymorphism in all tribes. In 3 populations (Gavião, Suruí, and Zoró) a negative disequilibrium was also detected between the insertion-deletion signal peptide markers and the XbaI polymorphism. In the whole sample of Amerindians 14 of the 24 (58%) possible 4-marker extended haplotypes were identified, but only haplotype 2 (5' beta SP*24/*X+/*M+/*E+) and haplotype 5 (5' beta SP*27/*X-/*M+/*E+) were shared by all tribes. No associations between plasma lipid levels or body mass index and these polymorphisms were observed in this sample.

Humans are among the most genetically variable species in existence. The advent of new genetic tools for analyzing this variation has uncovered even greater variability than previously recognized. These genetic data, available at multiple biological levels, are yielding new insights into population structure, population history, and evolutionary dynamics. This review highlights several issues in human diversity studies utilizing samples drawn from studies of South American populations.

A review is made of G6PD population surveys conducted in 4,558 European-derived, 2,484 admixed Black/Indian/White or Black/White, and 10,298 Indian subjects living in South America. Despite the fact that twice more Amerindians than Whites had been examined, no autochtonous variant was found among them, while seven different types (besides the most common Gd*B, Gd*A, Gd*A- and Gd*Med) were observed among the Whites. We also describe two new mutations in the G6PD molecule (Farroupilha, 977 C-->A and Lages, 40 G-->A), bringing the number of mutants characterized to 98. G6PD Lages is the most 5' mutation detected thus far. G6PD Seattle, previously found in the United States and Italy, seems to occur in other European countries and was observed by us in five independent Brazilian families.

Despite considerable investigation, two main questions on the origin of Native Americans remain the topic of intense debate-namely, the number and time of the migration(s) into the Americas. Using the 720 available Amerindian mtDNA control-region sequences, we reanalyzed the nucleotide diversity found within each of the four major mtDNA haplogroups (A-D) thought to have been present in the colonization of the New World. We first verified whether the within-haplogroup sequence diversity could be used as a measure of the haplogroup's age. The pattern of shared polymorphism, the mismatch distribution, the phylogenetic trees, the value of Tajima's D, and the computer simulations all suggested that the four haplogroups underwent a bottleneck followed by a large population expansion. The four haplogroup diversities were very similar to each other, offering a strong support for their single origin. They suggested that the beginning of the Native Americans' ancestral-population differentiation occurred approximately 30,000-40,000 years before the present (ybp), with a 95%-confidence-interval lower bound of approximately 25,000 ybp. These values are in good agreement with the New World-settlement model that we have presented elsewhere, extending the results initially found for haplogroup A to the three other major groups of mtDNA sequences found in the Americas. These results put the peopling of the Americas clearly in an early, pre-Clovis time frame.

In the circulation, non-esterified fatty acids are transported by albumin which also facilitates their removal from donor cells and uptake into receptor cells. We have studied whether genetic variations in the albumin molecule can affect its in vivo fatty acid-binding properties. The fatty acids bound to 25 structurally different variants and to their wildtype counterparts, isolated from heterozygous carriers, were determined gas chromatographically. The variants were proalbumins, albumins with single amino acid substitutions and glycosylated or truncated albumins. In eight cases the total amount bound to the variants was diminished (0.4-0.8-fold), and in seven cases the load was increased to 1.3 or more of normal. Twenty-one fatty acids were quantitated, and for 19 alloalbumins significant deviations from normal were found. Usually, changes in total and individual fatty acid binding were of the same type, but several exceptions to this rule was found. The glycosylated albumin Casebrook showed the largest changes, the total load and the amount of bound palmitate was 8.6 and 14 times, respectively, the normal. The most pronounced changes and the majority of cases of increased binding were caused by molecular changes in domain III. Mutations in domain I, II and the propeptide resulted in smaller effects, if any, and these were often reductions in binding.

Sequence data from the first hypervariable segment of the mitochondrial DNA control region of 124 subjects belonging to three African-Brazilian and three Brazilian Indian populations were compared with information related to 12 protein genetic loci from 601 persons living in the same localities. There is high diversity among the mtDNA sites, and the most variable in one ethnic group are not the most variable in the other. No differences in gene diversity between populations within ethnic groups were observed, but the Indians showed a reduced variability. Much more interpopulation variation was observed in the mtDNA data than in the protein set. The relationships obtained for the six populations, however, are the same regardless whether mtDNA or protein loci are considered. African-Brazilians from Porto Alegre and Salvador, situated 3,000 km apart, are more similar to each other than both are to Paredão, despite the geographical proximity between Porto Alegre and Paredão, which are just 50 km apart. The tree topology in relation to the three Indians groups, on the other hand, is that expected when languages, culture, and geography are considered.

Information concerning the HLA-A and -B loci was considered in relation to 3796 Amerindians living in 39 places in South America, data related to HLA-C being based on a smaller subset of 2989 persons distributed among 33 localities. Synthetic gene frequency maps were then constructed using principal-components analysis. Clearly significant longitudinal (principal component 1) and latitudinal (principal components 1, 2, and 3) clines were observed, most probably indicating ancient migration routes.

We have studied the hypervariable D1S80 locus in 185 individuals from five South American Indian tribes, integrating these results with previous investigations. Three alleles (*18, *24 and *30) were common to all tribes, but their frequencies varied between northern and southern populations. Brazilian tribes have a high frequency of *30 (average 35%) while in Argentinian and Chilean Indian populations this allele is present, on average, in 7% of the chromosomes only. Allele *24, the most common in other ethnic groups, was observed in 10% and 25% of northern and southern Amerindians respectively. Genetic distance and dendrogram analyses placed the Argentinian and Chilean tribes closer to Brazilian Caucasians, suggesting non-Indian admixture among them.

Data related to ten protein genetic loci expressed in blood obtained from four South American black populations were compared with data from seven African countries. Estimates of admixture among South American blacks were revised, and several indexes of gene diversity and genetic distances between the 11 populations were calculated. The admixture values and genetic relationships observed among the South American black communities conform well with those expected on historical grounds, and they show only moderate reductions in genetic diversity.

We have studied the hypervariable locus D1S80 in 75 white and 53 black Brazilians from Porto Alegre, a southern Brazilian population, and in 50 Brazilian Indians from the Xavante and Zoró tribes. Allele frequencies were significantly different among the three ethnic groups, mainly because of the higher frequencies of alleles *21, *22, *28, and *34 and the lower frequency of allele *18 in individuals of African ancestry and the higher frequencies of alleles *18 and *30 in Brazilian Indians. In the Indian group a restriction in the number of alleles (7) and genotypes (15) was found. The data suggest that the D1S80 locus is a useful interpopulation marker. This is the first report of its allele frequencies in Amerindians.

Information related to 31 protein genetic systems was obtained for 307 individuals affiliated with the Cinta Larga, Karitiana, Surui and Kararaô Indians of northern Brazil. In terms of genetic distances the Cinta Larga showed more similarities with the Karitiana (both are Tupi-speaking tribes), while at a more distant level the Surui clustered with the Kararaô. The latter, a Cayapo subgroup, showed a completely different genetic constitution from the other subgroups of this same tribe. Both the Kararaô and Karitiana are small, remnant populations, and their gene pools have presumably been severely affected by random and founder effects. These results were incorporated with those of 25 other Amazonian Indian tribes, and analysis by two multivariate techniques confirmed a previously observed geographical dichotomy, suggesting either that the Amazon river constitutes a barrier to north-south gene flow or that latitudinally different past migrations entered the region from the west.

A review is made of the Gm haplotype distribution in 60 groups of Eskimos, North, Central and South American Indians, totaling 22,808 individuals. Differences were observed in the shapes of the distribution of Gm*ag and the other markers. Nearly identical values for FST and average heterozygosities were obtained in the North+Central/South comparisons. North-South and Southwest/Northeast clinal differences were observed in the Americas using correspondence factorial analysis. The two haplotypes mainly responsible for these differences are Gm*axg and Gm*abOst. When the populations are classified by language groups, besides the recognized differences between Eskimos and Athabaskan (Na-Dene) speakers compared with Amerinds, others are found. For instance, Uto-Aztecan speakers of the United States and Mexico differ in Gm frequencies from the Nuclear Chibchan, Macro-Arawak, and Carib speakers of Central and South America. The notion of a homogeneous Amerind genetic pool does not conform with these and other results.

Specimens from three species of the Callicebus moloch group--C. moloch (N = 80), C. brunneus (N = 166), and C. cupreus (N = 23)--were studied. Twenty genetic loci were investigated through electrophoresis, genetic distances were estimated, and the results compared with the available cytogenetic data. Low values of genetic distance were encountered, contrasting with relatively large chromosome differences. We propose that recent karyotypic rearrangements, rather than other Pleistocene events, were the major evolutionary mechanisms determining speciation in these three taxa.

Electrophoretic surveys of 7794 individuals from different regions of Brazil and a study of subjects with hemolytic anemia have disclosed 9 putative G6PD variants in addition to the B, A, A-, and Mediterranean types. No variants were found among the 3739 Brazilian Indians tested. Four variants underwent DNA analysis. Three were identified with the Mediterranean, Seattle, and Anaheim types, but the fourth variant was previously undescribed and we propose to designate it G6PD São Borja.

DNA samples from 60 Mapuche Indians, representing 39 maternal lineages, were genetically characterized for (1) nucleotide sequences of the mtDNA control region; (2) presence or absence of a nine base duplication in mtDNA region V; (3) HLA loci DRB1 and DQA1; (4) variation at three nuclear genes with short tandem repeats; and (5) variation at the polymorphic marker D2S44. The genetic profile of the Mapuche population was compared to other Amerinds and to worldwide populations. Two highly polymorphic portions of the mtDNA control region, comprising 650 nucleotides, were amplified by the polymerase chain reaction (PCR) and directly sequenced. The 39 maternal lineages were defined by two or three generation families identified by the Mapuches. These 39 lineages included 19 different mtDNA sequences that could be grouped into four classes. The same classes of sequences appear in other Amerinds from North, Central, and South American populations separated by thousands of miles, suggesting that the origin of the mtDNA patterns predates the migration to the Americas. The mtDNA sequence similarity between Amerind populations suggests that the migration throughout the Americas occurred rapidly relative to the mtDNA mutation rate. HLA DRB1 alleles 1602 and 1402 were frequent among the Mapuches. These alleles also occur at high frequency among other Amerinds in North and South America, but not among Spanish, Chinese or African-American populations. The high frequency of these alleles throughout the Americas, and their specificity to the Americas, supports the hypothesis that Mapuches and other Amerind groups are closely related.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparative study of 13 blood genetic systems and pelage color variation was performed in four wild populations of Alouatta belzebul. The animals from the west bank of the Tocantins River showed less color variation than those from the east bank, as well as less than those from Tocantins Island. The blood genetic markers, however, revealed an opposite pattern of variation. A previously undescribed morphological variant (completely red) was observed in one specimen of the east bank, where pelage color of the local population varied from completely black to completely red. Levels of heterozygosity and inter- and intralocus variances for the blood systems are compared with those observed in five other species of New World primates.

Allele frequencies for the orosomucoid 1 (ORM1), orosomucoid 2 (ORM2), alpha-2-HS-glycoprotein (AHSG) and complement component I (IF) loci were studied in 393 individuals of three Brazilian Indian tribes. In the ORM1 locus only two alleles were observed among the Urubu-Kaapor, while five were found among the Pacaás Novos. The frequency of ORM1*1 was similar in these two tribes (0.734 and 0.715, respectively) but departed more markedly among the Parakanã (0.870). Variation for ORM2 locus was found among the Pacaás Novos only, with ORM2*3 being observed in just three individuals. A new variant (AHSG*PN) was found in the AHSG system. Frequency for AHSG*1 was unexpectedly low in the three tribes, especially, among the Pacaás Novos, where the prevalence (0.145) is the lowest considering other data reported thus far. For IF locus, variability was also restricted to only one trible (Urubu-Kaapor) and attributed to a new polymorphic allele, IF* A3.

Data are presented on electrophoretic variants of 25 polypeptides found in the blood serum and erythrocytes, in 812 individuals from three Amerindian tribes, the Pano, the Baniwa, and the Kanamari. Two "private polymorphisms" were encountered, of PEPB in the Pano and CAII in the Baniwa. A single example of a different PEPB variant was encountered in the Baniwa, and two possible examples of an unstable variant of HGB A2 in the Kanamari. In addition, the well-known A variant of ACP1, the Duarte variant of GALT, the 2 variant of Hp and the 2 variant of PGM1 occurred in polymorphic proportions in all three tribes, and the TFDChi variant was present as a polymorphism in the Baniwa. These data have recently been incorporated into a treatment which concludes that the eight electrophoretically-defined "private polymorphisms" thus far encountered in Amerindian tribes can be explained by a mutation pressure of 0.7 x 10(-5)/locus/generation on the assumption of neutrality of the phenotypes in question (Neel and Thompson, '78).

A total of 505 individuals belonging to four populations of three Brazilian Indian tribes were variously studied in relation to 34 genetic systems, and the results were compared with South American Indian averages and five other Tupi populations. Rare variants (CdE of the Rh system, PGM211-1, Cp A-CAY1, serum cholinesterase2 C5+ and some Gm combinations) were observed with varying prevalences, and the three tribes showed different degrees of departure (28%-40% of differences of 10% or more in gene frequencies) from South American Indian averages. People from two communities who speak the same language and are labelled as belonging to the same tribe (Asurini) showed a large degree of genetic differentiation. Another of the tribes studied (Urubu-Kaapor) link through genetic distance analyses with two other tribes from the north of the continent, forming a distinct microevolutionary unit. These features emphasize the peculiarities of the genetic variation in populations with a hunter-gatherer, rudimentary agriculture type of economy.

Conventional horizontal starch-gel electrophoresis in four buffer systems and structural studies were performed on four albumin variants, and the findings were compared with similar previous data. Albumins Coari I and Porto Alegre I have a previously unreported amino acid substitution (glutamic acid replaced by lysine at position 358, denoted 358 Glu----Lys). The alteration in albumin Porto Alegre II (501 Glu----Lys) is the same as that found for three alloalbumins of Asiatic origin, designated Vancouver, Birmingham, and Adana. Albumin Oriximiná I has the same exchange as albumin Maku (541 Lys----Glu). Some of these findings can be explained only by the occurrence of independent mutations at the same site in the albumin gene. They also point to a third cluster of mutations in that gene, indicating hypermutability in some of its segments.

Nine Carib and eight Tupi groups were studied for a minimum of eight common polymorphic systems and compared in terms of genetic distances using the methods of Nei and Edwards. Two levels of genetic information were distinguished, one with a maximum of 20 loci and another with a maximum of 12 loci considered. The dendrograms produced consistent, reproducible results, independent of the method used, when a minimum of ten polymorphic systems were included in the analysis. Irrespective of the number of systems or the method used, the Tupi showed two to three times higher average interpopulation genetic distances than the Carib groups, which may be due to their lower average population sizes, allowing for the action of genetic drift and/or founder effects, as these two sets of populations do not differ significantly in geographic range, years of contact with non-Indians, or degree of acculturation.

Data on blood group, serum protein, erythrocyte enzyme, and histocompatibility antigen (HLA) traits are presented for the Waiãpi, a Tupi-speaking tribe of the Brazilian and French Guianas. Intra- and intertribal comparisons have been made between these data, and previously published data from French Guiana, from another Tupi tribe and from other tribes of neighboring areas, and from the continent as a whole. For this purpose, we have modified the usual measure of genetic distance to obtain a value which is independent of the number of loci being considered. The intertribal genetic distances do not correlate with linguistic affinity. Social differences, which may have affected the rate of drift from the continental mean, correlate better with genetic distances.

Blood samples from 509 Macushi and 623 Wapishana Amerindians of of Northern Brazil and Southern Guyana have been analyzed with reference to the occurrence of rare variants and genetic polymorphisms of the following 25 systems: (i) Erythrocyte enzymes: acid phosphatase-1, adenosine deaminase, adenylate kinase-k, carbonic anhydrase-1, carbonic anhydrase-2, esterase A1,2,3, esterase D, galactose-1-phosphate uridyltransferase, isocitrate dehydrogenase, lactate dehydrogenase, malate dehydrogenase, nucleoside phosphorylase, peptidase A, peptidase B, phosphoglucomutase 1, phosphoglucomutase 2, phosphogluconate dehydrogenase, phosphohexoseisomerase, triosephosphate isomerase and (ii) Serum proteins: albumin, ceruloplasmin, haptoglobin, hemoglobin A2 and transferrin. Fifteen different rare variants were detected, involving 11 of these systems. In addition, a previously undescribed variant of ESA 1,2,3 which achieves polymorphic proportions in both these tribes is described. Excluding this variant, the frequency of rare variants is 1.1/1000 in 12510 determinations in the Macushi and 4.7/1000 in 15396 determinations in the Wapishana. The ESA 1,2,3 polymorphism was not observed in 382 Makiritare, 232 Yanomama, 146 Piaroa, 404 Cayapo, 190 Kraho and 112 Moro. Irregularities in the intratribal distribution of this polymorphism in the Macushi and Wapishana render a decision as to the tribe of origin impossible at present. Gene frequencies are also given for previously described polymorphisms of 5 systems: haptoglobin, phosphoglucomutase 1, erythrocyte acid phosphatase, esterase D, and galactose-1-phosphate-uridyl-transferase.

A total of 136 individuals were studied in relation to 31 genetic systems, and the results were compared with South American Indian averages and previous surveys on the Wayana of French Guiana and Surinam. The information was afterwards integrated with data from other Carib groups, and two types of genetic distances (Nei's and Edwards') were calculated a) between five groups, considering ten systems; and b) between nine groups, using five systems. The two measures of genetic distances correlated well (Spearman's correlation coefficient around 0.70), and there was good agreement between the geographical and genetic distances. All analyses indicated a peripheral position for the Apalai-Wayana and their distinctiveness from the Wayana of French Guiana and Surinam, suggesting that intertribal fusions may play an important role in the genetic differentiation of these populations.

A total of 562 individuals living in four villages of two Brazilian Indian tribes (Cayapo and Krahó) was studied in relation to blood groups ABO, MNSs, , Rh, Lewis, Duffy, Kidd and Diego; haptoglobin, Gc, acid phosphatase and phosphoglucomutase types. These results were compared with those obtained previously among the Xavante, and the inhabitants of three other Cayapo villages, all of whom speak Ge languages; the ranges in gene frequencies observed in a representative series of South American Indians from all over the continent were also compiled. The Ge Indians are characterized by low frequencies of RZ, medium frequencies of R1, R2, R0, or r, Jka and PGM1/1, and high frequencies of Gc2 and ACPA when compared with other South American tribes. Genetic distance analyses based on six loci indicate that the intratribal variability observed among Cayapo is of the same order of magnitude as those obtained among the Xavante and Krahó, being much less pronounced than those observed among the Yanomama and Makiritare. The intertribal differences within this linguistic group are much less pronounced than those encountered among tribes that speak more differentiated languages.