Francesc Calafell

Human mitochondrial DNA variation and the origin of Basques

The hypervariable segment I of the control region of the mtDNA (positions 16024–16383) was PCR‐amplified from mouth scrape and hairs and sequenced in 45 unrelated individuals of pure matrilineal Basque descent. Twenty‐seven different sequences were found, of which 21 are unique to the Basques. The allelic partition observed, together with resampling experiments, suggested that much more variation remained to be discovered.

Short tandem repeat polymorphism evolution in humans

Forty-five dinucleotide short tandem repeat polymorphisms were typed in ten large samples of a globally distributed set of populations. Although these markers had been selected for high heterozygosity in European populations, we found them to be sufficiently informative for linkage analysis in non-Europeans. Heterozygosity, mean number of alleles, and mean number of private alleles followed a common trend: they were highest in the African samples, were somewhat lower in Europeans and East Asians, and were lowest in Amerindians. Genetic distances also reflected this pattern, and distances modelled after the stepwise mutation model yielded trees that were less in agreement with other genetic and archaeological evidence than distances based on differentiation by drift (FST). Genetic variation in non-Africans seems to be a subset of that in Africans, supporting the replacement hypothesis for the origin of modern humans.

Sequence diversity of the control region of mitochondrial DNA in Tuscany and its implications for the peopling of Europe.

The control region of mitochondrial DNA has been widely studied in various human populations. This paper reports sequence data for hypervariable segments 1 and 2 of the control region from a population from southern Tuscany (Italy). The results confirm the high variability of the control region, with 43 different haplotypes in 49 individuals sampled. The comparison of this set of data with other European populations allows the reconstruction of the population history of Tuscany. Independent approaches, such as the estimation of haplotype diversity, mean pairwise differences, genetic distances and discriminant analysis, place the Tuscan sample in an intermediate position between sequences from culturally or geographically isolated regions of Europe (Sardinia, the Basque Country, Britain) and those from the Middle East. In spite of the remarkable genetic homogeneity in Europe, a degree of variability is shown by local European populations and homogeneity increases with the relative isolation of the population. The pattern of mitochondrial variation in Tuscany indicates the persistence of an ancient European component subsequently enriched by migrational waves, possibly from the Middle East.

Population Genetics of Y-Chromosome Short Tandem Repeats in Humans

Abstract. Eight human short tandem repeat polymorphisms (STRs) also known as microsatellites—DYS19, DYS388, DYS390, DYS391, DYS392, DYS393, DYS389I, and DYS389II, mapping in the Y chromosome—were analyzed in two Iberian samples (Basques and Catalans). Allele frequency distributions showed significant differences only for DYS392. Fst and gene diversity index (D) were estimated for the Y STRs. The values obtained are comparable to those of autosomal STR if corrections for the smaller effective population size on the Y chromosome are taken into account. This suggests that Y-chromosome microsatellites might be as useful as their autosomal counterparts to both human population genetics and forensics. Our results also reinforce the hypothesis that selective sweeps in the Y chromosome in recent times are unlikely. Haplotypes combining five of the loci were constructed for 71 individuals, showing 29 different haplotypes. A haplotype tree was constructed, from which an estimate of 7,000 to 60,000 years for the age of the Y-chromosome variation in Iberia was derived, in accordance with previous estimates obtained with mtDNA sequences and nuclear markers.

A tale of two islands: population history and mitochondrial DNA sequence variation of Bioko and São Tomé, Gulf of Guinea

The hypervariable segment I of the control region of the mtDNA was sequenced in 45 unrelated individuals from Bioko and 50 from São Tomé, two islands in the Gulf of Guinea that have had very different settlement patterns: Bioko was colonized around 10000 BP, while São Tomé was first settled by the Portuguese, who brought African slaves to the island. Two different patterns of sequence variation are evident and are also clearly a consequence of their very different demographic histories. The Bubi present a low genetic diversity and it is likely that the island was colonized by a small number of individuals with small later migration. São Tomeans might be considered a subset of a mainland African population relocated to the island. They present high genetic diversity with a high number of sequences being shared with many continental populations. This study, with knowledge of the population history in island populations, strengthens the genetic approach to unravel past demographic events.

Mitochondrial DNA variation and the origin of the Europeans

Abstract Sequences from the mitochondrial DNA (mtDNA) control region were analyzed in nine European and West Asian populations. They showed low genetic heterogeneity when compared to world populations. However, a Caucasoid population tree displayed a robust east-west gradient. Within-population diversity (ascertained through various parameters) and mean pairwise differences declined from east to west, in a pattern compatible with ancient population migration and expansion from the Middle East. Estimated expansion times indicate a Paleolithic event with important differences among populations according to their geographical position and thus a slower tempo than previously believed. The replacement of Neanderthals by anatomically modern humans, fully compatible with the present results, may have been a slower and more complex process than cultural change suggests.

Allele Frequencies for 20 Microsatellites in a Worldwide Population Survey

20 microsatellite polymorphisms: HUMHPRT, HUMD3S1358, HUMTH01, HUMACPP, HUMVWF, HUMD16S310, HUMD4S243, HUMTPO, HUMFES/FPS, HUMF13A1, HUMDHFRP2, HUMD11S2010, HUMD13S767, HUMD9S926, HUMD2S1328, HUMD14S306, HUMD18S848, HUMD5S818, HUMD7S820 and HUMFGA were analyzed in a worldwide survey covering five continents and allele frequencies are given. There is a high heterogeneity in allele frequencies among continents. A neighbor-joining tree based on Fst distance shows a pattern of differentiation that may reflect the role of drift in the development of genetic differences among humans. The variation found between continents confirms the usefulness of tetranucleotide microsatellites in human genetic variation studies.

Hla evidence for the lack of genetic heterogeneity in Basques

To examine the possible internal heterogeneity within the Basque population, nine samples typed for several HLA loci were compiled and HLA‐A, B, C and DR loci were analysed. First, the shared features of HLA in Basques were analysed by principal component analysis and genetic distances. Two major Basque dialect groups (‘French’ and ‘Spanish’) were considered. FST statistics were computed and corrected for sampling intensity. The dialectal and political division did not seem to differentiate these two groups genetically. Analysis of Molecular Variance also failed to show consistently significant genetic variance components between French and Spanish Basques. Thus, in this particular example, linguistic diversity does not seem to correlate with a genetic stratification.

Allele Frequencies in a Worldwide Survey of a CA Repeat in the First Intron of the CFTR Gene

A dinucleotide CA repeat within intron 1 of the CFTR gene has recently been identified. We have determined the allele frequencies of this polymorphism in samples from 18 populations covering all major geographical areas, with a total of 1,816 chromosomes. When considering allele distributions, African populations presented a wider range of alleles than other populations and also presented higher expected heterozygosities. Analysis of molecular variance showed that 8.04% of the genetic variance in this locus could be attributed to differences among populations. We concluded that the polymorphism in the CA repeat in intron 1 of the CFTR gene is highly informative in populations from all geographical regions of the world. Thus, it can be applied to family studies of unknown mutations causing cystic fibrosis (CF) and can provide valuable information for genetic counseling. Moreover, its analysis should be included in the haplotypic analysis of known CF mutations.

Do Basque- and Caucasian-speaking populations share non-Indo-European ancestors?

Genetic evidence is consistent with the view that the Indo-European languages were propagated in Europe by the diffusion of early farmers. The existence of phylogenetic relationships between European populations speaking other languages has been proposed on linguistic and archaeological grounds, and is here tested by analyzing allele frequencies at ten polymorphic protein and blood group loci. Genetic distances between speakers of Basque and Caucasian languages are compared with those between controls, i.e. contiguous populations speaking Indo-European and Altaic. Although some statistical tests show an excess of genetic similarity between Basque and South Caucasian speakers, most results do not support their common origin. If the Basques and the Caucasian-speaking populations share common ancestors, recent evolutionary phenomena must have caused divergence between them, so that their gene frequencies do not appear more similar now than those of random pairs of populations separated by the same geographic distance.