Immunoglobulin allotypes (GM and KM) in Basques from Spain: Approach to the origin of the Basque population

ROSARIO CALDER6N, CONCEPCION VIDALES, JOSE A. PENA,1 ANA PEREZ-MIRANDA, AND JEAN-MICHEL DUGOUJON

Abstract GM and KM immunoglobulin (Ig) allotypes have been tested in 310 autochthonous Basques from the three subpopulations of Vizcaya, Guipuzcoa, and Alava, Spain. They are compared with allotypes occurring in autochthonous French Basques, some Pyrenean subpopulations in France, and European populations. The analysis suggests that the Basque subpopulations show noticeable genetic distances between them and with other European populations. The genetic similarity between Basques and European populations is greater in the Basques from France than in the Basques from Spain. The genetic distances between Basque subpopulations in Spain fit well with the different historical levels of the spatial implantation of the Basque language. Guipuzcoa, the Basque province with the highest number of Basque-speaking people, shows the most genetic distinctiveness. The main underlying cause of this spatial genetic pattern seems to be admixture with surrounding populations. Our results do not support the hypothesis that Basques are a relict population of ancient Europeans. They might be a consequence of the colonization of the Basque area by a long-distance migrating group, probably a small Neolithic North Caucasian population that introduced agriculture in the region. They experienced early, rapid demographic growth, and they did not breed with the few hunter-gatherers wandering throughout the area. The North Caucasian migrants could have admixed with North Asian groups dating from many centuries before. Furthermore, Basques present polymorphic frequencies of a common African haplotype, suggesting that they have not been completely isolated from populations of Africa. However, another focus of the African haplotype has been detected in Central Asia, and the Basque frequencies alternatively might be due to North Asian groups.

KEY WORDS: IMMUNOGLOBULIN ALLOTYPES, BASQUES, GENETIC DIVERSITY,EVOLUTIONARY GENETIC HISTORY

The GM system is a valuable tool for the investigation of the history and genetic diversity of populations. The qualitative and quantitative differences between GM haplotypes characterize major ethnic groups, making this system a useful tool for genetic anthropology and for the determination of the degree of admixture in a given population and detection of gene flow between them (Steinberg and Cook 1981; Schanfield and Van Loghem 1986; Cavalli-Sforza et al. 1994). In addition, immunoglobulin (Ig) genes (or genes linked to the GM system), can influence disease susceptibility (Whittingham and Propert 1986; Black et al. 1995; Dugoujon and Cambon-Thomsen 1995). GM allotypes are genetically determined variants restricted to one IgG subclass and are located on the heavy chains (constant domains of the IgGl, IgG2 and IgG3 subclasses). The KM allotypes are situated on constant region of the K light chain. Because the genes coding for heavy chains are closely linked, the allotypes GIM, G2M, and G3M are inherited in fixed combinations or haplotypes (de Lange 1989).

The Basques have traditionally been considered one of the most anthropologically interesting populations in Europe and were selected recently as part of a group of 42 worldwide populations on the basis of geographic, ethnic, and linguistic criteria by Cavalli-Sforza et al. (1994). Previous characterization of the Basque population needs clarification and more in-depth consideration by a selection of geographically structured Basque subpopulations.

The first anthropological speculations about the origins of the Basques and their biological affinities to other human populations were expressed as early as the nineteenth century by the Swedish anatomist and anthropologist A.R. Retzius (1796-1860). Morphometric features, mainly from the craniofacial region, were used, and those results turned out to establish relationships between Basques and Finns, also a non-Indo-European language speaking population (Calderon and Rebato 1997). With these statements the Basques entered for the first time into the history of anthropology in Europe. A reliable way to find genealogical relatives of the Basque language among Caucasian language families also was suggested by the French anthropologist P. Broca, and his line of thinking was developed in his work Sur l'origine et repartition de la langue Basque (1875). However, it is difficult to find out who first posed the question of a Basque-Caucasian genetic relationship because in the ancient world the Greek term leres had been attached to Georgia in the Caucasus as well as to the Iberian peninsula (Urreiztieta-Rivera 1980).

Nowadays the information available on the genetics of Basques in Spain is remarkable, and the population structure of Spanish Basques has been described for almost all traditional genetic polymorphisms. The results are spread over a great number of published papers, and our database lists 369 papers from 1937 to 1994. Data concerning highly polymorphic genetic systems are significantly far less abundant. This observation can be made regarding HLA population studies (Arnaiz-Villena et al. 1981; Garcia de Masdevall et al. 1982; Calderon, Wentzel et al. 1993; Martinez-Laso et al. 1995) because frequencies and genetic patterns on Ig allotypes have not been published yet. Comparatively, Basques from France have been analyzed for both HLA antigens (Dausset et al. 1972; De Mouzon et al. 1980) and Ig allotype determinants (Dugoujon, Clayton et al. 1989; Hazout et al. 1991). In Spain few Ig allotype studies have been carried out hitherto, and most of the findings concern GIM(I), G1M(2), G3M(5), and KM(I) factors (Hernandez 1982; Almuzara et al. 1991). GM haplotype frequencies in some Spanish regions can be found in the papers by Schanfield et al. (1981) and Moreno and Matsumoto (1991).