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.     

Analysis of mtDNA variation in African populations reveals the most ancient of all human continent-specific haplogroups.

mtDNA sequence variation was examined in 140 Africans, including Pygmies from Zaire and Central African Republic (C.A.R.) and Mandenkalu, Wolof, and Pular from Senegal. More than 76% of the African mtDNAs (100% of the Pygmies and 67.3% of the Senegalese) formed one major mtDNA cluster (haplogroup L) defined by an African-specific HpaI site gain at nucleotide pair (np) 3592. Additional mutations subdivided haplogroup L into two subhaplogroups, each encompassing both Pygmy and Senegalese mtDNAs. A novel 12-bp homoplasmic insertion in the intergenic region between tRNA(Tyr) and cytochrome oxidase I (COI) genes was also observed in 17.6% of the Pygmies from C.A.R. This insertion is one of the largest observed in human mtDNAs. Another 25% of the Pygmy mtDNAs harbored a 9-bp deletion between the cytochrome oxidase II (COII) and tRNA(Lys) genes, a length polymorphism previously reported in non-African populations. In addition to haplogroup L, other haplogroups were observed in the Senegalese. These haplogroups were more similar to those observed in Europeans and Asians than to haplogroup L mtDNAs, suggesting that the African mtDNAs without the HpaI np 3592 site could be the ancestral types from which European and Asian mtDNAs were derived. Comparison of the intrapopulation sequence divergence in African and non-African populations confirms that African populations exhibit the largest extent of mtDNA variation, a result that further supports the hypothesis that Africans represent the most ancient human group and that all modern humans have a common and recent African origin. The age of the total African variation was estimated to be 101,000-133,000 years before present (YBP), while the age of haplogroup L was estimated at 98,000-130,000 YBP. These values substantially exceed the ages of all Asian- and European-specific mtDNA haplogroups.     

Mitochondrial gene diversity in the common vole Microtus arvalis shaped by historical divergence and local adaptations

The phylogeography of the common vole (Microtus arvalis) was examined by analysing mitochondrial DNA (mtDNA) sequence variation in 1044 base pairs (bp) of the cytochrome b (cytb) gene and in 322 bp of the control region (ctr) among 106 individuals from 58 locations. The geographical distribution of four previously recognized cytb evolutionary lineages in Europe was refined and a new lineage was found in southern Germany. All lineages were distributed allopatrically, except in one sample that was probably located in a contact zone. The occurrence of several lineages in the Alps is in keeping with their recent recolonization from distinct sources. The translation of 84 cytb DNA sequences produced 33 distinct proteins with relationships that differed from those of the DNA haplotypes, suggesting that the mtDNA lineages did not diverge in response to selection. In comparison with M. agrestis, a neutrality test detected no overall evidence for selection in the cytb gene, but a closer examination of a structural model showed that evolutionarily conserved and functionally important positions were often affected. A new phylogeographical test of random accumulation of nonsynonymous mutations generated significant results in three lineages. We therefore conclude that the molecular diversity of cytb in M. arvalis is overall the result of the demographic history of the populations, but that there have been several episodes of local adaptation to peculiar environments.     

SIMCOAL 2.0: a program to simulate genomic diversity over large recombining regions in a subdivided population with a complex history

We present an extension of the program SIMCOAL, which allows for simulation of the genomic diversity of samples drawn from a set of populations with arbitrary patterns of migrations and complex demographic histories, including bottlenecks and various modes of demographic expansion. The main additions to the previous version include the possibility of arbitrary and heterogeneous recombination rates between adjacent loci and multiple coalescent events per generation, allowing for the simulation of very large samples and recombining genomic regions, together with the simulation of single nucleotide polymorphism data with frequency ascertainment bias. AVAILABILITY: http://cmpg.unibe.ch/software/simcoal2/.     

Human diversity: our genes tell where we live

A detailed genetic analysis of more than a thousand human subjects clusters them into five groups corresponding to major geographical regions. This new study shows that self-reported ancestry is a good predictor of one's genetic make-up.     

Incorporating genotypes of relatives into a test of linkage disequilibrium.

Genetic data from autosomal loci in diploids generally consist of genotype data for which no phase information is available, making it difficult to implement a test of linkage disequilibrium. In this paper, we describe a test of linkage disequilibrium based on an empirical null distribution of the likelihood of a sample. Information on the genotypes of related individuals is explicitly used to help reconstruct the gametic phase of the independent individuals. Simulation studies show that the present approach improves on estimates of linkage disequilibrium gathered from samples of completely independent individuals but only if some offspring are sampled together with their parents. The failure to incorporate some parents sharply decreases the sensitivity and accuracy of the test. Simulations also show that for multiallelic data (more than two alleles) our testing procedure is not as powerful as an exact test based on known haplotype frequencies, owing to the interaction between departure from Hardy-Weinberg equilibrium and linkage disequilibrium.     

High variability and non-neutral evolution of the mammalian <Emphasis Type="Italic">avpr1a</Emphasis> gene

Background  

The arginine-vasopressin 1a receptor has been identified as a key determinant for social behaviour in Microtus voles, humans and other mammals. Nevertheless, the genetic bases of complex phenotypic traits like differences in social and mating behaviour among species and individuals remain largely unknown. Contrary to previous studies focusing on differences in the promotor region of the gene, we investigate here the level of functional variation in the coding region (exon 1) of this locus.     

Fine-scale genetic structure and dispersal in the common vole (Microtus arvalis)

The genetic structure and demography of local populations is tightly linked to the rate and scale of dispersal. Dispersal parameters are notoriously difficult to determine in the field, and remain often completely unknown for smaller organisms. In this study, we investigate spatial and temporal genetic structure in relation to dispersal patterns among local populations of the probably most abundant European mammals, the common vole (Microtus arvalis). Voles were studied in six natural populations at distances of 0.4-2.5 km in three different seasons (fall, spring, summer) corresponding to different life-history stages. Field observations provided no direct evidence for movements of individuals between populations. The analysis of 10 microsatellite markers revealed a persistent overall genetic structure among populations of 2.9%, 2.5% and 3% FST in the respective season. Pairwise comparisons showed that even the closest populations were significantly differentiated from each other in each season, but there was no evidence for temporal differentiation within populations or isolation by distance among populations. Despite significant genetic structure, assignment analyses identified a relatively high proportion of individuals as being immigrants for the population where they were captured. The immigration rate was not significantly lower for females than for males. We suggest that a generally low and sex-dependent effective dispersal rate as the consequence of only few immigrants reproducing successfully in the new populations together with the social structure within populations may explain the maintenance of genetic differentiation among populations despite migration.     

Bipolar gene flow in deep-sea benthic foraminifera

Despite its often featureless appearance, the deep-ocean floor includes some of the most diverse habitats on Earth. However, the accurate assessment of global deep-sea diversity is impeded by a paucity of data on the geographical ranges of bottom-dwelling species, particularly at the genetic level. Here, we present molecular evidence for exceptionally wide distribution of benthic foraminifera, which constitute the major part of deep-sea meiofauna. Our analyses of nuclear ribosomal RNA genes revealed high genetic similarity between Arctic and Antarctic populations of three common deep-sea foraminiferal species (Epistominella exigua, Cibicides wuellerstorfi and Oridorsalis umbonatus), separated by distances of up to 17, 000 km. Our results contrast with the substantial level of cryptic diversity usually revealed by molecular studies, of shallow-water benthic and planktonic marine organisms. The very broad ranges of the deep-sea foraminifera that we examined support the hypothesis of global distribution of small eukaryotes and suggest that deep-sea biodiversity may be more modest at global scales than present estimates suggest.     

Enhanced AFLP genome scans detect local adaptation in high-altitude populations of a small rodent (Microtus arvalis)

Adaptation to adverse environmental conditions such as high altitude requires physiological and/or morphological changes. Genome scans provide a means to identify the genetic basis of such adaptations without previous knowledge about the particular genetic variants or traits under selection. In this study, we scanned 3027 amplified fragment length polymorphisms (AFLP) in four populations of the common vole Microtus arvalis for loci associated with local adaptation and high altitude. We investigated voles from two populations at high elevation (~2000 m a.s.l.) representing the upper limit of the altitudinal distribution of the species and two geographically close low-altitude populations (<600 m a.s.l.). Statistical analysis incorporated a new Bayesian F(ST) outlier approach specifically developed for AFLP markers, which considers the intensity of AFLP bands instead of mere presence/absence and allows to derive population-based estimates of allele frequencies and F(IS) values. Computer simulations showed that this approach increases the statistical power of the detection of AFLP markers under selection almost to the power of single nucleotide polymorphism (SNP) data without compromising specificity. Our enhanced genome scan resulted in 20 prime candidate markers for positive selection, which show mostly extremely high allele frequency differences between the low- and high-altitude populations. The comparison of global- and pairwise-enhanced genome scans demonstrated further that very strong selective signatures may also be associated with single populations suggesting the importance of local adaptation in alpine populations of common voles.