Using mitochondrial DNA to test the hypothesis of a European post-glacial human recolonization from the Franco-Cantabrian refuge.

It has been proposed that the distribution patterns and coalescence ages found in Europeans for mitochondrial DNA (mtDNA) haplogroups V, H1 and H3 are the result of a post-glacial expansion from a Franco-Cantabrian refuge that recolonized central and northern areas. In contrast, in this refined mtDNA study of the Cantabrian Cornice that contributes 413 partial and 9 complete new mtDNA sequences, including a large Basque sample and a sample of Asturians, no experimental evidence was found to support the human refuge-expansion theory. In fact, all measures of gene diversity point to the Cantabrian Cornice in general and the Basques in particular, as less polymorphic for V, H1 and H3 than other southern regions in Iberia or in Central Europe. Genetic distances show the Cantabrian Cornice is a very heterogeneous region with significant local differences. The analysis of several minor subhaplogroups, based on complete sequences, also suggests different focal expansions over a local and peninsular range that did not affect continental Europe. Furthermore, all detected clinal trends show stronger longitudinal than latitudinal profiles. In Northern Iberia, it seems that the highest diversity values for some haplogroups with Mesolithic coalescence ages are centred on the Mediterranean side, including Catalonia and South-eastern France.

Mitochondrial DNA variation in Mauritania and Mali and their genetic relationship to other Western Africa populations.

Mitochondrial DNA (mtDNA) variation was analyzed in Mauritania and Mali, and compared to other West African samples covering the considerable geographic, ethnic and linguistic diversity of this region. The Mauritanian mtDNA profile shows that 55% of their lineages have a west Eurasian provenance, with the U6 cluster (17%) being the best represented. Only 6% of the sub-Saharan sequences belong to the L3A haplogroup a frequency similar to other Berber speaking groups but significantly different to the Arabic speaking North Africans. The historic Arab slave trade may be the main cause of this difference. Only one HV west Eurasian lineage has been detected in Mali but 40% of the sub-Saharan sequences belong to cluster L3A. The presence of L0a representatives demonstrates gene flow from eastern regions. Although both groups speak related dialects of the Mande branch, significant genetic differences exist between the Bambara and Malinke groups. The West African genetic variation is well structured by geography and language, but more detailed ethnolinguistic clustering suggest that geography is the main factor responsible for this differentiation.

Y chromosome and mitochondrial DNA characterization of Pasiegos, a human isolate from Cantabria (Spain).

Mitochondrial DNA sequences and Y chromosome haplotypes were characterized in Pasiegos, a human isolate from Cantabria, and compared with those of other Cantabrian and neighbouring Northern Spain populations. Cantabria appears to be a genetically heterogeneous community. Whereas Lebaniegos do not differ from their eastern Basque and western Asturian and Galician neighbours, Pasiegos and other non-Lebaniego Cantabrians show significant differences with all of them. Pasiegos are peculiar for their high frequencies of Y chromosomal markers (E-M81) with North African assignation, and Y chromosomal (R-SRY2627) and mtDNA (V, I, U5) markers related to northern European populations. This dual geographic contribution is more in agreement with the complex demographic history of this isolate, as opposed to recent drift effects. The high incidence in Cantabrians with pre-V and V mtDNA haplotypes, considered as a signal of Postglacial recolonization in Europe from south-western refugees, points to such refugees as a better candidate population than Basques for this expansion. However, this does not discount a conjoint recolonization.

A predominant European ancestry of paternal lineages from Canary Islanders.

We genotyped 24 biallelic sites and 5 microsatellites from the non-recombining portion of the Y chromosome in 652 males from the Canary Islands. The results indicate that, contrary to mtDNA data, paternal lineages of the current population are overwhelmingly (>90%) of European origin, arguing for a highly asymmetric pattern of mating after European occupation. However, the presence of lineages of indisputable African assignation demonstrates that an aboriginal background still persists (<10%). On the basis of distribution and dating of some of these lineages we derived a genetic perspective of settlement processes of the archipelago in two stages, congruent with anthropological, archaeological and linguistic findings.

Mitochondrial DNA characterisation of European isolates: the Maragatos from Spain.

Mitochondrial DNA analysis confirms that Maragatos from Spain are a genetically isolated human group. Genetic distances between Maragatos and the comparison samples are significantly different even with the León sample (P<0.001) which shares the same geographic area as the Maragatos. Although the north-African haplogroup U6 is present in them, their attributed Berber origin is weakened, as this haplogroup is also detected in surrounding populations with which, in addition, Maragatos have the smaller genetic distances. These U6 haplotypes are ascribed to a pre-historic African colonisation that influenced all the Iberian Peninsula. The presence of Neolithic haplogroups in this sample suggests that their isolation culture was not absolute until recent times.

Major genomic mitochondrial lineages delineate early human expansions.

BACKGROUND: The phylogeographic distribution of human mitochondrial DNA variations allows a genetic approach to the study of modern Homo sapiens dispersals throughout the world from a female perspective. As a new contribution to this study we have phylogenetically analysed complete mitochondrial DNA(mtDNA) sequences from 42 human lineages, representing major clades with known geographic assignation. RESULTS: We show the relative relationships among the 42 lineages and present more accurate temporal calibrations than have been previously possible to give new perspectives as how modern humans spread in the Old World. CONCLUSIONS: The first detectable expansion occurred around 59,000-69,000 years ago from Africa, independently colonizing western Asia and India and, following this southern route, swiftly reaching east Asia. Within Africa, this expansion did not replace but mixed with older lineages detectable today only in Africa. Around 39,000-52,000 years ago, the western Asian branch spread radially, bringing Caucasians to North Africa and Europe, also reaching India, and expanding to north and east Asia. More recent migrations have entangled but not completely erased these primitive footprints of modern human expansions.

Structure and evolution of the mitochondrial DNA complete control region in the Drosophila subobscura subgroup.

The complete A + T-rich region of mitochondrial DNA (mtDNA) has been cloned and sequenced in the species of the Drosophila subobscura subgroup D. subobscura, D. madeirensis and D. guanche. Comparative analysis of these sequences with others already published has identified new sequence motifs that are conserved in Drosophila and other insects. A putative bi-directional promoter and a stop signal are proposed to be involved in the primary mtDNA strand replication of Drosophila. This region strongly resolves relationships of the species included in a phylogenetic analysis, both for closely related species and also at deeper phylogenetic levels when only the left and central domains are taken into account.

Phylogeography of the human mitochondrial haplogroup L3e: a snapshot of African prehistory and Atlantic slave trade.

The mtDNA haplogroup L3e, which is identified by the restriction site +2349 MboI within the Afro-Eurasian superhaplogroup L3 (-3592 HpaI), is omnipresent in Africa but virtually absent in Eurasia (except for neighbouring areas with limited genetic exchange). L3e was hitherto poorly characterised in terms of HVS-I motifs, as the ancestral HVS-I type of L3e cannot be distinguished from the putative HVS-I ancestor of the entire L3 (differing from the CRS by a transition at np 16223). An MboI screening at np 2349 of a large number of Brazilian and Caribbean mtDNAs (encompassing numerous mtDNAs of African ancestry), now reveals that L3e is subdivided into four principal clades, each characterised by a single mutation in HVS-I, with additional support coming from HVS-II and partial RFLP analysis. The apparently oldest of these clades (transition at np 16327) occurs mainly in central Africa and was probably carried to southern Africa with the Bantu expansion(s). The most frequent clade (transition at np 16320) testifies to a pronounced expansion event in the mid-Holocene and seems to be prominent in many Bantu groups from all of Africa. In contrast, one clade (transition at np 16264) is essentially restricted to Atlantic western Africa (including Cabo Verde). We propose a tentative L3e phylogeny that is based on 197 HVS-I sequences. We conclude that haplogroup L3e originated in central or eastern Africa about 46,000 (+/-14,000) years ago, and was a hitchhiker of much later dispersal and local expansion events, with the rise of food production and iron smelting. Enforced migration of African slaves to the Americas translocated L3e mitochondria, the descendants of which in Brazil and the Caribbean still reflect their different regional African ancestries.

Phylogeographic patterns of mtDNA reflecting the colonization of the Canary Islands.

Although the Canary Islands were settled by humans, possibly of Berber origin, as late as 2500 years ago, the precise course and numbers of early migrations to the archipelago remain controversial. We have therefore analysed mtDNA variation (HVS-I as well as selected RFLP sites) in 300 individuals from the seven Canary Islands. The distribution and variation across the islands in a specific mtDNA clade of Northwest African ancestry suggest that there was one dominant initial settlement process that affected all the islands, from east to west. This indicates that a certain genetic affinity of present-day Canary Islanders to Northwest African Berbers mainly stems from the autochthonous population rather than slaves captured on the neighbouring African coast. The slave trade after the European conquest left measurable, though minor, traces in the mtDNA pool of the Canary Islands, which in its majority testifies to the European immigration.

Expanding informativeness of microsatellite motifs through the analysis of heteroduplexes: a case applied to Solanum tuberosum.

The incorporation of heteroduplex analysis into conventional strategies for the study of polymorphisms at microsatellite loci has allowed us to obtain information useful in determining genetic diversity and relationships among organisms. We have chosen, as a model for the testing of this strategy, several Solanum tuberosum varieties cultivated on Tenerife Island (Canary Archipelago) and a (TCT)(n) microsatellite located in intron I from the gene for granule-bound starch synthase. The data obtained confirm the high degree of agreement between molecular and farmer taxonomy.

Molecular diagnosis of alkaptonuria mutation by analysis of homogentisate 1,2 dioxygenase mRNA from urine and blood.

Alkaptonuria (AKU) is caused by lack of homogentisate 1, 2 dioxygenase (HGO) activity. From the complete sequence of a human HGO cDNA, primers were designed in order to obtain reverse transcription-polymerase chain reaction products from tissues with ectopic transcription amenable to diagnostic analysis. A search for mutations in HGO cDNA was performed in an AKU family using urine and blood samples. The results show complete cosegregation (Z = 6.32; theta = 0) between a C-->T transition at position 817 of the human HGO cDNA and AKU. This mutation predicts a Pro-->Ser replacement at amino acid 230, and generates an EcoRV site.

Mitochondrial DNA analysis of northwest African populations reveals genetic exchanges with European, near-eastern, and sub-Saharan populations.

Genetic studies have emphasized the contrast between North African and sub-Saharan populations, but the particular affinities of the North African mtDNA pool to that of Europe, the Near East, and sub-Saharan Africa have not previously been investigated. We have analysed 268 mtDNA control-region sequences from various Northwest African populations including several Senegalese groups and compared these with the mtDNA database. We have identified a few mitochondrial motifs that are geographically specific and likely predate the distribution and diversification of modern language families in North and West Africa. A certain mtDNA motif (16172C, 16219G), previously found in Algerian Berbers at high frequency, is apparently omnipresent in Northwest Africa and may reflect regional continuity of more than 20,000 years. The majority of the maternal ancestors of the Berbers must have come from Europe and the Near East since the Neolithic. The Mauritanians and West-Saharans, in contrast, bear substantial though not dominant mtDNA affinity with sub-Saharans.

Population genetic structure and colonization sequence of Drosophila subobscura in the Canaries and Madeira Atlantic Islands as inferred by autosomal, sex-linked and mtDNA traits.

The genetic structure in Atlantic Islands and continental populations of Drosophila subobscura has been studied using autosomal and sex-linked allozymes and mitochondrial DNA (mtDNA) haplotypes. From the data it is deduced that whereas the Canary islands have long been isolated, the neighboring island of Madeira has been subjected to continuous migration from the mainland. In addition, sex-linked allozymes and mtDNA data show a large divergence between the geologically younger western islands of the Canarian Archipelago and the older central ones, finding strong founder effects in the former. Divergence rates of sex-linked and mitochondrial genes relative to autosomic loci several times higher than expected under neutrality have been explained by differential migration between sexes. The Canarian Archipelago colonization fits in well with a stepping-stone model of a directional east-west migration that parallels the geological origin of these Islands.

Blood group polymorphisms in the Canary Islands.

Human samples from the seven Canary Islands were studied for the following polymorphic red cell blood group systems: ABO, RH, MNSs, FY and P. In contrast to the intra-insular homogeneity found, inter-insular heterogeneity was observed for ABO, RH and FY. The observed blood group allelic systems were within the range of European populations, with some minor African contribution.

Sub-Saharan influence on the Canary Islands population deduced from G6PD gene sequence analysis.

In a screening of glucose-6-phosphate dehydrogenase (G6PD) A variants in the Canary Islands and northwest African populations by electrophoresis and posterior gene sequencing, the common A+ 376G and A- 202A/376G and the rare A- 376G/968C mutations were found. In addition, three new silent C-->T transitions have been detected at nucleotides 759 (exon 7), 1338 (exon 11), and 1573 (exon 13). Canary Island and North African samples share sub-Saharan haplotypes with Equatorial Guineans. The slave trade seems the most probable origin of the African haplotypes found in the Canary Islands.

Genetic relationship between the Canary Islanders and their African and Spanish ancestors inferred from mitochondrial DNA sequences.

Nucleotide sequences of the hypervariable segment I of the control region of the mtDNA were determined in 101 individuals: 54 Canary Islanders, 18 North African Berbers, 18 Spanish mainlanders and 11 sub-Saharan Guineans. In spite of the fact that only members of the Fang tribe were analysed, nucleotide diversity in Guineans (theta x 100 = 2.33) is one of the highest found in African populations. Estimates of genetic contribution to the Canarians from their putative parental populations based on mtDNA (43.25 +/- 1.38% Berbers, 35.54 +/- 0.55% Spanish, 21.21 +/- 1.92% Guineans) showed an important North African substrate. These mtDNA results, when compared with data based on nuclear markers, point to a strong male female asymmetry, 75% of the Spanish nuclear contribution was due to males and practically all the Berber and Guinean was due to females. These results are in agreement with the way that the Canary Islands were conquered. Pairwise difference distributions in Guineans and Berbers are compatible with the model of populations in expansion. Departures from a Poisson distribution for the Canarians and Spanish can be explained by admixture and the way of sampling respectively.

Human enzyme polymorphism in the Canary Islands. VI. Northwest African influence.

The genetic polymorphism of eight red cell enzymes was analyzed in population samples from the Northwest African Continent and from the South of Spain in order to study their genetic relationships with the Canarian population. The Moroccan, Berber and Spanish populations, although geographically more distant from the Canary Islands than the Saharan and Mauritanian ones, are genetically more closely related to the Canarian population. The glucose-6-phosphate dehydrogenase Gc allele earlier found only in the Canary Islands was detected in the Berber sample. The Spanish, Berber and African Black contributions to the Canarian hybrid population was estimated to 70, 20 and 10%, respectively.

Latitudinal differences in sex chromosome inversions, sex linked allozymes, and mitochondrial DNA variation in Drosophila subobscura.

Mitochondrial DNA, sex linked allozymes, and chromosome A gene arrangement data, from eight European natural populations of Drosophila subobscura, were analyzed to determine the existence of latitudinal clines. Strong north-south correlations with latitude were found for gene arrangements and for the Hbdh and 6Pgdh allozymes. Gametic associations between the A2 gene arrangement, the Hbdh96 and the 6Pgdh96 alleles, point out some kind of epistatic interaction. At mtDNA level, the Hae III, A variant did not show a previously found north-south clinal variation.

Human enzyme polymorphism in the Canary Islands. V. Western Islands.

Autochthonous human samples of the three westernmost islands of the Canarian Archipelago, La Palma, Gomera, and Hierro, have been analyzed for eight red cell polymorphic enzymes. Only a small intra and inter-insular differentiation exists among these three islands. However, a marked heterogeneity is found when all seven islands of the Archipelago are compared by Nei's genetic distances [1972]. Nevertheless, there is no correlation between genetic and geographic distances. Historical factors could explain the frequency similarities of some distant islands. The rare variant GD*A+Negroid allele, and the endemic GD*Gc allele, previously found in other islands, have also been detected in this survey.

Mitochondrial DNA evolution in the obscura species subgroup of Drosophila.

Mitochondrial DNA (mtDNA) restriction site maps for nine species of the Drosophila obscura subgroup and for Drosophila melanogaster were established. Taking into account all restriction enzymes (12) and strains (45) analyzed, a total of 105 different sites were detected, which corresponds to a sample of 3.49% of the mtDNA genome. Based on nucleotide divergences, two phylogenetic trees were constructed assuming either constant or variable rates of evolution. Both methods led to the same relationships. Five differentiated clusters were found for the obscura subgroup species, one Nearctic, represented by Drosophila pseudoobscura, and four Palearctic, two grouping the related triads of species Drosophila subobscura, Drosophila madeirensis, Drosophila obscura, Drosophila subsilvestris, and two more represented by one species each, Drosophila bifasciata, and Drosophila tristis. The different Palearctic clusters are as distant between themselves as with the Nearctic one. For the related species D. subobscura, D. madeirensis, and D. guanche, the pair D. subobscura-D. madeirensis is the closest one. The relationships found by nucleotide divergence were confirmed by differences in mitochondrial genome size, with related species sharing similar genome lengths and differing from the distant ones. The total mtDNA size range for the obscura subgroup species was from 15.5 kb for D. pseudoobscura to 17.1 for D. tristis.