Hydrochemical characterization, spatial distribution, and geochemical controls on arsenic and boron in waters from arid Arica and Parinacota, northern Chile.

The livelihood of inhabitants from rural agricultural valleys in the arid Arica and Parinacota Region, northernmost Chile, strongly depends on water from high altitude rainfall and runoff to lower elevation areas. However, elevated arsenic, boron, and other potentially harmful elements compromise water quality, especially in rural areas. Samples (n = 90) of surface, underground, cold, geothermal springs, and treated and raw tap water were studied to assess water quality and to determine the main geochemical controls on water composition, origin, and geochemical evolution along dominant flowpaths. Water from major river basins across the region (Lluta, San Jose, Codpa-Chaca, Camarones and Altiplanicas) were collected for hydrogeochemical analysis of a suite of major and trace elements, δD and δ18O. Our new dataset was supplemented by hydrochemical data (n > 1500 data points) from secondary sources. Results show that 72% of the collected samples had As >10 µg/L (WHO drinking water provisional guideline) and affected 44% of the studied waters used for drinking (n = 32). Based on Chilean irrigation guidelines, elevated salinity (EC > 0.75 mS/cm) affected 80% of sampled waters, which were also impacted by high B (89% > 0.75 mg/L), and As (31% > 50 µg/L). Water composition was strongly controlled by geothermal water and freshwater mixing in high altitude areas. Magnitude and fate of As and B concentration was determined by the geothermal input type. Highest As (~21 mg/L) was associated with circum-neutral Na-Cl waters in Camarones basin, while lower As (~5 mg/L) with acid SO4 waters in Lluta basin. Additionally, evaporative concentration and sediment-water interactions were shown to control the level of As in surface and groundwaters downstream. This works provides a comprehensive analysis and a conceptual model of geochemical controls on regional water compositions, contributing to better understanding the geochemical processes underpinning the water quality challenges in northern Chile.

Neoproterozoic copper cycling, and the rise of metazoans.

The rise of animal life is temporally related to the increased availability of oxygen in the hydrosphere and atmosphere during the Neoproterozoic. However, the earliest metazoans probably needed relatively low oxygen concentrations, suggesting additional environmental and/or biochemical developments were involved. Copper was required in the exploitation of oxygen by the evolving animals, through the development of respiratory proteins and the extracellular matrix required for structural support. We synthesize global data demonstrating a marked enrichment of copper in the Earth's crust that coincided with the biological use of oxygen, and this new biological use of copper. The copper enrichment was likely recycled into the surface environment by weathering of basalt and other magmatic rocks, at copper liberation rates up to 300 times that of typical granitic terrain. The weathering of basalts also triggered the Sturtian glaciation, which accelerated erosion. We postulate that the coincidence of a high availability of copper, along with increased oxygen levels, for the first time during the Neoproterozoic supported the critical advances of respiration and structural support in evolving animals.

Temporal variation in phenetic affinity of early Upper Egyptian male cranial series.

We carried out an exploratory historical biology study using temporally distinguished groups of predynastic-Early Dynastic male crania from the region of Upper Egypt. The objectives were, first, to determine the overall pattern of phenetic affinity between temporally sequential series and in relation to the earliest series and, second, to explore the possible meanings of the pattern of relationship to sociohistorical change. The cranial series were designated early predynastic, late predynastic, terminal predynastic, and Dynasty I. Craniometric phenetic affinity was ascertained using Mahalanobis distances; a 5% level of probability was chosen for significance. The distance matrix values were ordered into hierarchies of dissimilarity from each series (distance hierarchies) and tabulated for time-successive groups, including the temporally earliest series (i.e., serialized by time). The principal observations were as follows. The overall pattern was not one in which the values between all series were statistically insignificant; nor was it one of consistent sequential increase of biological distance from the earliest series. There was a notable and statistically significant distance between the early and late predynastic groups, with the late and terminal predynastic groups mutually having the lowest and statistically insignificant distances with each other. The value between the terminal predynastic and Dynasty I series was generally larger than the values between other groups and was statistically significant. The overall pattern is possibly consistent with archeological interpretations that postulate increasing intraregional interactions during the late and terminal predynastic periods and the rise of an Egyptian state that eventually included northern Egypt.

Discovery of a 25-cm asteroid clast in the giant Morokweng impact crater, South Africa.

Meteorites provide a sample of Solar System bodies and so constrain the types of objects that have collided with Earth over time. Meteorites analysed to date, however, are unlikely to be representative of the entire population and it is also possible that changes in their nature have occurred with time. Large objects are widely believed to be completely melted or vaporized during high-angle impact with the Earth. Consequently, identification of large impactors relies on indirect chemical tracers, notably the platinum-group elements. Here we report the discovery of a large (25-cm), unaltered, fossil meteorite, and several smaller fragments within the impact melt of the giant (> 70 km diameter), 145-Myr-old Morokweng crater, South Africa. The large fragment (clast) resembles an LL6 chondrite breccia, but contains anomalously iron-rich silicates, Fe-Ni sulphides, and no troilite or metal. It has chondritic chromium isotope ratios and identical platinum-group element ratios to the bulk impact melt. These features allow the unambiguous characterization of an impactor at a large crater. Furthermore, the unusual composition of the meteorite suggests that the Morokweng asteroid incorporated part of the LL chondrite parent body not represented by objects at present reaching the Earth.

Diachronic patterns of dental hypoplasias and vault porosities during the predynastic in the Naqada region, Upper Egypt.

The diachronic pattern of the frequencies of linear enamel hypoplasias and porotic hyperostosis was studied in temporally separated samples of adult predynastic Egyptian remains from the Naqada region, Upper Egypt. The samples covered a period of increasing population density and social complexity as well as decreasing Nile flooding in Egypt. First and second molars were evaluated for hypoplasias in material from the Naqada I, II, and III periods; sample sizes were 13, 30, and 25, respectively, for the first molar, and 11, 28, and 24 for the second molar. Cranial vaults were examined for porotic hyperostosis using several approaches; sample sizes were 26, 66, and 51 for Naqada I, II and III, respectively. Linear regression showed a decreasing trend for several variables: for the individual frequency of first molar hypoplasias (rho = 0.025), the vault porosity score, which indicates the severity of the lesions (rho < 0.001), and the extent score, which indicates the number of superior vault bones having porosities (rho < 0.001). Logistic regression showed a temporal decline in the percentage of crania per sample having any vault porosities and only higher grade lesions (rho < 0.012 and rho < 0.003, respectively). Lesions of the second molar showed no directional trend. The results contrast with the common observation that these skeletal markers usually increase in contexts of increasing population density and social complexity.

Polymorphism and divergence in the beta-globin replication origin initiation region.

DNA sequence polymorphism and divergence was examined in the vicinity of the human beta-globin gene cluster origin of replication initiation region (IR), a 1.3-kb genomic region located immediately 5' of the adult-expressed beta-globin gene. DNA sequence variation in the replication origin IR and 5 kb of flanking DNA was surveyed in samples drawn from two populations, one African (from the Gambia, West Africa) and the other European (from Oxford, England). In these samples, levels of nucleotide and length polymorphism in the IR were found to be more than two times as high as adjacent non-IR-associated regions (estimates of per-nucleotide heterozygosity were 0.30% and 0.12%, respectively). Most polymorphic positions identified in the origin IR fall within or just adjacent to a 52-bp alternating purine-pyrimidine ((RY)n) sequence repeat. Within- and between-populations divergence is highest in this portion of the IR, and interspecific divergence in the same region, determined by comparison with an orthologous sequence from the chimpanzee, is also pronounced. Higher levels of diversity in this subregion are not, however, primarily attributable to slippage-mediated repeat unit changes, as nucleotide substitution contributes disproportionately to allelic heterogeneity. An estimate of helical stability in the sequenced region suggests that the hypervariable (RY)n constitutes the major DNA unwinding element (DUE) of the replication origin IR, the location at which the DNA duplex first unwinds and new strand synthesis begins. These findings suggest that the beta-globin IR experiences a higher underlying rate of neutral mutation than do adjacent genomic regions and that enzyme fidelity associated with the initiation of DNA replication at this origin may be compromised. The significance of these findings for our understanding of eukaryotic replication origin biology is discussed.

Minisatellite mutational processes reduce F(st) estimates.

We have used a new method for binning minisatellite alleles (semi-automated allele aggregation) and report the extent of population diversity detectable by eleven minisatellite loci in 2,689 individuals from 19 human populations distributed widely throughout the world. Whereas population relationships are consistent with those found in other studies, our estimate of genetic differentiation (F(st)) between populations is less than 8%, which is lower than comparative estimates of between 10%-15% obtained by using other sources of polymorphism data. We infer that mutational processes are involved in reducing F(st) estimates from minisatellite data because, first, the lowest F(st) estimates are found at loci showing autocorrelated frequencies among alleles of similar size and, second, F(st) declines with heterozygosity but by more than predicted assuming simple models of mutation. These conclusions are consistent with the view that minisatellites are subject to selective or mutational constraints in addition to those expected under simple step-wise mutation models.

The population genetics of the haemoglobinopathies.

The haemoglobinopathies are the commonest single-gene disorders known, almost certainly because of the protection they provide against malaria, as attested by a number of observations. The geographical distributions of malaria and haemoglobinopathies largely overlap, and microepidemiological surveys confirm the close relationship between them. For two of the commonest disorders, haemoglobin S and alpha(+)-thalassaemia, there is also good clinical evidence for protection against malaria morbidity. However, not all the evidence appears to support this view. In some parts of the world malaria and haemoglobinopathies are not, and never have been, coexistent. It is also difficult to explain why the majority of haemoglobinopathies appear to be recent mutations and are regionally specific. Here we argue that these apparent inconsistencies in the malaria hypothesis are the result of processes such as genetic drift and migration and of demographic changes that have occurred during the past 10,000 years. When these factors are taken into account, selection by malaria remains the force responsible for the prevalence of the haemoglobinopathies.

Seroprevalence of Borrelia burgdorferi in dogs in Alabama, USA.

A random sample of private small-animal practices in Alabama submitted sera from dogs with known tick contact. A total of 579 samples from the three geographic regions of the state were collected (58% of the targeted sample size). Sera were screened for antibodies to Borrelia burgdorferi using an indirect fluorescent antibody (IFA) test which had a sensitivity and specificity of greater than 90%. Anti-B burgdorferi titers of > or = 1:64 were considered to be positive, based on results from B. burgdorferi-inoculated dogs. Ten of the 579 samples (1.7%) were positive, and titers ranged from 1:64 to 1:512. Seropositive dogs were found throughbout the state, and there was no significant difference in seroprevalence by region (Mantel-Haenszel chi 2, P = 0.85). These results indicate that the seroprevalence for canine Lyme disease in Alabama is low and that use of the canine Lyme disease vaccine is not justified.

High diversity of alpha-globin haplotypes in a Senegalese population, including many previously unreported variants.

RFLP haplotypes at the alpha-globin gene complex have been examined in 190 individuals from the Niokolo Mandenka population of Senegal: haplotypes were assigned unambiguously for 210 chromosomes. The Mandenka share with other African populations a sample size-independent haplotype diversity that is much greater than that in any non-African population: the number of haplotypes observed in the Mandenka is typically twice that seen in the non-African populations sampled to date. Of these haplotypes, 17.3% had not been observed in any previous surveys, and a further 19.1% have previously been reported only in African populations. The haplotype distribution shows clear differences between African and non-African peoples, but this is on the basis of population-specific haplotypes combined with haplotypes common to all. The relationship of the newly reported haplotypes to those previously recorded suggests that several mutation processes, particularly recombination as homologous exchange or gene conversion, have been involved in their production. A computer program based on the expectation-maximization (EM) algorithm was used to obtain maximum-likelihood estimates of haplotype frequencies for the entire data set: good concordance between the unambiguous and EM-derived sets was seen for the overall haplotype frequencies. Some of the low-frequency haplotypes reported by the estimation algorithm differ greatly, in structure, from those haplotypes known to be present in human populations, and they may not represent haplotypes actually present in the sample.

VNTR alleles associated with the alpha-globin locus are haplotype and population related.

The human alpha-globin complex contains several polymorphic restriction-enzyme sites (i.e., RFLPs) linked to form haplotypes and is flanked by two hypervariable VNTR loci, the 5' hypervariable region (HVR) and the more highly polymorphic 3'HVR. Using a combination of RFLP analysis and PCR, we have characterized the 5'HVR and 3'HVR alleles associated with the alpha-globin haplotypes of 133 chromosomes, and we here show that specific alpha-globin haplotypes are each associated with discrete subsets of the alleles observed at these two VNTR loci. This statistically highly significant association is observed over a region spanning approximately 100 kb. With the exception of closely related haplotypes, different haplotypes do not share identically sized 3'HVR alleles. Earlier studies have shown that alpha-globin haplotype distributions differ between populations; our current findings also reveal extensive population substructure in the repertoire of alpha-globin VNTRs. If similar features are characteristic of other VNTR loci, this will have important implications for forensic and anthropological studies.

Molecular and population genetic analysis of allelic sequence diversity at the human beta-globin locus.

Allelic sequence polymorphism at the beta-globin locus was investigated in a group of 36 Melanesians. A 3-kilobase fragment containing the gene and its flanking regions was sequenced in 60 normal (beta A) and 12 thalassemic (intron 1, position 5, G-->C) chromosomes. Haplotype relationships between linked polymorphisms were derived by allele-specific PCR amplification and sequencing. Seventeen nucleotide polymorphisms and 2 length variants were identified, and these sites segregated as 17 sequence haplotypes in the normal chromosomes. This haplotype diversity is higher than that expected on the basis of the nucleotide polymorphism observed and is probably due to recombination and gene conversion. Nucleotide diversity at synonymous sites in the sample is 0.14%, suggesting an average age of sequence divergence of approximately 450,000 years, consistent with that expected for a neutrally evolving human nuclear locus.

A computer simulation study of VNTR population genetics: constrained recombination rules out the infinite alleles model.

Extensive allelic diversity in variable numbers of tandem repeats (VNTRs) has been discovered in the human genome. For population genetic studies of VNTRs, such as forensic applications, it is important to know whether a neutral mutation-drift balance of VNTR polymorphism can be represented by the infinite alleles model. The assumption of the infinite alleles model that each new mutant is unique is very likely to be violated by unequal sister chromatid exchange (USCE), the primary process believed to generate VNTR mutants. We show that increasing both mutation rates and misalignment constraint for intrachromosomal recombination in a computer simulation model reduces simulated VNTR diversity below the expectations of the infinite alleles model. Maximal constraint, represented as slippage of single repeats, reduces simulated VNTR diversity to levels expected from the stepwise mutation model. Although misalignment rule is the more important variable, mutation rate also has an effect. At moderate rates of USCE, simulated VNTR diversity fluctuates around infinite alleles expectation. However, if rates of USCE are high, as for hypervariable VNTRs, simulated VNTR diversity is consistently lower than predicted by the infinite alleles model. This has been observed for many VNTRs and accounted for by technical problems in distinguishing alleles of neighboring size classes. We use sampling theory to confirm the intrinsically poor fit to the infinite alleles model of both simulated VNTR diversity and observed VNTR polymorphisms sampled from two Papua New Guinean populations.

Demographic reductions and genetic bottlenecks in humans: minisatellite allele distributions in Oceania.

Polynesians have lower heterozygosities at minisatellite VNTR (Variable Number of Tandem Repeat) loci than have Melanesians; this has been taken as evidence of population-size bottlenecks during the colonisation of Polynesia. We have analysed the allelic distribution of several minisatellite loci in the population of Rapa, a Polynesian island that is known to have undergone a demographic reduction of approximately 95% since first contact with European explores 200 years ago, leaving a surviving population of 120. We found that the minisatellite diversity of this population does not differ significantly from that of other Polynesian populations, and appears consistent with the neutral expectation of diversity assuming the infinite alleles model. This suggests that the demographic crisis that Rapa underwent did not perturb the allele distribution to the extent that the tests used here could detect. Thus we cannot say that a demographic change of this magnitude constitutes a genetic bottleneck detectable at these loci. The reduced diversity seen in Polynesia must therefore be explained either by more severe bottlenecks as might be expected during colonisation, or else by other causes.

Why are some genetic diseases common? Distinguishing selection from other processes by molecular analysis of globin gene variants.

Various processes (selection, mutation, migration and genetic drift) are known to determine the frequency of genetic disease in human populations, but so far it has proved almost impossible to decide to what extent each is responsible for the presence of a particular genetic disease. The techniques of gene and haplotype analysis offer new hope in addressing this issue, and we review relevant studies of three haemoglobinopathies: sickle cell anaemia, and alpha and beta thalassaemia. We show how for each disease it is possible to recognize a pattern of regionally specific mutations, found in association with one or a few haplotypes, that is best explained as the result of selection; other patterns are due to population migration and genetic drift. However, we caution that such conclusions can be drawn in special circumstances only. In the case of the haemoglobinopathies it is possible because a selective agent (malaria) was already suspected, and the investigations could be carried out in relatively genetically homogenous populations whose migratory histories are known. Moreover, some data reviewed here suggest that gene conversion and the haplotype composition of a population may affect the frequency of a mutation, making interpretation of gene frequencies difficult on the basis of standard population genetics theory. Hence attempts to use the same approaches with other genetic diseases are likely to be frustrated by a lack of suitably untrammelled populations and by difficulties accounting for poorly understood genetic processes. We conclude that although this combination of molecular and population genetics is successful when applied to the study of haemoglobinopathies, it may not be so easy to apply it to the study of other genetic diseases.

The population genetics of the haemoglobinopathies.

The haemoglobinopathies are the commonest single gene disorders known, and are so common in some regions of the world that the majority of the population carries at least one genetic abnormality affecting the structure or synthesis of the haemoglobin molecule. The prevalence of the common haemoglobinopathies (the alpha- and beta-thalassaemias, HbS, HbC and HbE) is almost certainly a result of the protection they provide against malaria, as the epidemiological evidence reviewed in this chapter shows. World-wide, the distributions of malaria and the common haemoglobinopathies largely overlap, and micro-epidemiological surveys have confirmed the close relationship between the disorders. However, there are complications to this picture which appear to undermine the malaria hypothesis. First, in some areas, malaria and haemoglobinopathies are not coincident. Second, the malaria hypothesis does not easily explain why no two regions of the world have the same haemoglobinopathy or combination of haemoglobinopathies. The majority of mutations have arisen only once and are regionally specific. By using molecular characterization of mutations and the analysis of haplotypes on haemoglobinopathy-bearing chromosomes it is possible to show how a combination of selection by malaria, genetic drift and population movements can explain the first complication. In order to explain the second, we have argued that malaria selection has operated relatively recently on human populations (within the last 5000 years). The present distribution is then seen as the result of selection elevating sporadic mutations in local populations. In the absence of sufficient gene flow to spread all mutations to all populations, the consequence is a patchwork distribution of haemoglobinopathies. Given time, we would expect the mutations that protect and do not compromise the health of their carriers to become widely disseminated, but it is likely that human intervention will alter this process of natural selection.

The evolution of tandemly repetitive DNA: recombination rules.

Variable numbers of tandem repeats (VNTRs), which include hypervariable regions, minisatellites and microsatellites, can be assigned together with satellite DNAs to define a class of noncoding tandemly repetitive DNA (TR-DNA). The evolution of TR-DNA is assumed to be driven by an unbiased recombinational process. A simulation model of unequal exchange is presented and used to investigate the evolutionary persistence of single TR-DNA lineages. Three different recombination rules are specified to govern the expansion and contraction of a TR-DNA lineage from an initial array of two repeats to, finally, a single repeat allele, which cannot participate in a misalignment and exchange process. In the absence of amplification or selection acting to bias array evolution toward expansion, the probability of attaining a target array size is a function only of the initial number of repeats. We show that the proportions of lineages attaining a targeted array size are the same irrespective of recombination rule and rate, demonstrating that our simulation model is well behaved. The time taken to attain a target array size, the persistence of the target array, and the total persistence time of repetitive array structure, are functions of the initial number of repeats, the rate of recombination, and the rules of misalignment preceding recombinational exchange. These relationships are investigated using our simulation model. While misalignment constraint is probably greatest for satellite DNA it also seems important in accounting for the evolution of VNTR loci including minisatellites. This conclusion is consistent with the observed nonrandom distributions of VNTRs and other TR-DNAs in the human genome.

Phospholipase C-sensitive factor VII complexes in dog plasma.

We report the presence of a phospholipase c-sensitive activated factor VII complex in canine plasma after feeding a special diet. Low levels of complex was observed in the fasting state. The response to feeding in terms of activated factor VII varied markedly among the dogs investigated.

Population bottlenecks in Polynesia revealed by minisatellites.

Tandem-repetitive highly variable loci in the human genome (minisatellites) have been used in gene mapping and as DNA "fingerprints", but they have not yet found much application in population genetics. We have investigate the capacity of six minisatellites to discriminate between four populations in Oceania. We find that in comparison to Melanesians, Polynesians have a significant loss of heterozygosity (or gene diversity), not noted using more traditional markers. We show also that the number of alleles, the allele distribution and the mutation rates at the Polynesian minisatellite loci do not deviate from those predicted by the neutral mutation/infinite allele model. The low gene diversity is therefore likely to be a result of the maintenance of small population sizes and bottleneck effects during the colonization of the Pacific.