Genetic continuity in the Franco-Cantabrian region: new clues from autochthonous mitogenomes

Background

The Late Glacial Maximum (LGM), ∼20 thousand years ago (kya), is thought to have forced the people inhabiting vast areas of northern and central Europe to retreat to southern regions characterized by milder climatic conditions. Archaeological records indicate that Franco-Cantabria might have been the major source for the re-peopling of Europe at the beginning of the Holocene (11.5 kya). However, genetic evidence is still scarce and has been the focus of an intense debate.

Methods/Principal Findings

Based on a survey of more than 345,000 partial control region sequences and the analysis of 53 mitochondrial DNA (mtDNA) genomes, we identified an mtDNA lineage, HV4a1a, which most likely arose in the Franco-Cantabrian area about 5.4 kya and remained confined to northern Iberia.

Conclusions/Significance

The HV4a1a lineage and several of its younger branches reveal for the first time genetic continuity in this region and long-term episodes of isolation. This, in turn, could at least in part explain the unique linguistic and cultural features of the Basque region.     

The maternal legacy of Basques in northern navarre: New insights into the mitochondrial DNA diversity of the Franco-Cantabrian area

Autochthonous Basques are thought to be a trace from the human population contraction that occurred during the Last Glacial Maximum, based mainly on the salient frequencies and coalescence ages registered for haplogroups V, H1, and H3 of mitochondrial DNA in current Basque populations. However, variability of the maternal lineages still remains relatively unexplored in an important fraction of the Iberian Basque community. In this study, mitochondrial DNA diversity in Navarre (North Spain) was addressed for the first time. To that end, HVS-I and HVS-II sequences from 110 individuals were examined to identify the most relevant lineages, including analysis of coding region SNPs for the refinement of haplogroup assignment. We found a prominent frequency of subhaplogroup J1c (11.8%) in Navarre, coinciding with previous studies on Basques. Subhaplogroup H2a5, a putative autochthonous Basque lineage, was also observed in Navarre, pointing to a common origin of current Basque geographical groups. In contrast to other Basque subpopulations, comparative analyses at Iberian and European scales revealed a relevant frequency of subhaplogroup H3 (10.9%) and a frequency peak for U5b (15.5%) in Navarre. Furthermore, we observed low frequencies for maternal lineages HV0 and H1 in Navarre relative to other northern Iberian populations. All these findings might be indicative of intense genetic drift episodes generated by population fragmentation in the area of the Franco-Cantabrian refuge until recent times, which could have promoted genetic microdifferentiation between the different Basque subpopulations.     

The management of otherness beyond the state: integration policies and inclusive citizenship as a government paradigm in the Basque Country

The ethnic identity of second-generation immigrant youth has important implications for their association with, and integration in, receiving countries. This paper deals with the ethnic identity formation of second-generation Turkish immigrant youth in Germany, with particular attention paid to the notion of reactive ethnicity. While much of the literature discusses the ethnic retention of this specific group as unwillingness to integrate, this paper frames their ethnic identity formation as reactive ethnicity, which emerges in reaction to social exclusion. Utilizing a case study of Turkish students of disadvantaged schools, the article illustrates that reactive ethnicity is strongly linked to perceived discrimination and that it acquires characteristics of resistance when the dominant group denigrates and invalidates the immigrants' culture.     

Structuring the genetic heterogeneity of the Basque population: a view from classical polymorphisms

In this study we analyze 18 classical polymorphisms (ABO, Rh, MNSs, Lewis, P, Duffy, Kell, ADA, ESD, PGM1, PGD, AK1, ACP1, GLO1, HP, GC, TF, and PI) in over 2000 autochthonous individuals from 14 natural districts in three provinces of the Basque Country (Alava, Guipuzcoa, and Biscay). Heterogeneity analysis via the chi2 test and a calculation of F(ST) indicate that there is significant genetic heterogeneity between the Basque districts. The R matrix informs us that this heterogeneity is not significantly concentrated in a single district or in the districts of a single province, but is rather distributed among several districts belonging to the three provinces analyzed. We undertake to assess the influence of various historical, geographical, and cultural factors on the genetic structure of the Basque population. Analysis suggests that allele distribution is geographically patterned in the Basque Country. The gradient distributions observed in the case of some alleles (ABO*O, RH*cDE, RH*cde, MNS*MS, and ACP1*C) on the basis of Moran's autocorrelation coefficient I, along with the influence of the two main travel routes through the Basque Country (western route through Bilbao and eastern route through Vitoria), suggest that the gene flow tends toward the coast. As regards other factors considered (administrative division, repopulation processes, linguistic heterogeneity, and north vs. south cultural heterogeneity), we detected only a certain influence exerted by an old tribal differentiation (2000 B.P.), which would diminish with the passage of time.     

Paternal genetic history of the Basque population of Spain

This study examines the genetic variation in Basque Y chromosome lineages using data on 12 Y-short tandem repeat (STR) loci in a sample of 158 males from four Basque provinces of Spain (Alava, Vizcaya, Guipuzcoa, and Navarre). As reported in previous studies, the Basques are characterized by high frequencies of haplogroup R1b (83%). AMOVA analysis demonstrates genetic homogeneity, with a small but significant amount of genetic structure between provinces (Y-short tandem repeat loci STRs: 1.71%, p = 0.0369). Gene and haplotype diversity levels in the Basque population are on the low end of the European distribution (gene diversity: 0.4268; haplotype diversity: 0.9421). Post-Neolithic contribution to the paternal Basque gene pool was estimated by measuring the proportion of those haplogroups with a Time to Most Recent Common Ancestor (TMRCA) previously dated either prior (R1b, I2a2) or subsequent to (E1b1b, G2a, J2a) the Neolithic. Based on these estimates, the Basque provinces show varying degrees of post-Neolithic contribution in the paternal lineages (10.9% in the combined sample).     

Experimental evidence for genetic heritability of maternal hormone transfer to offspring

In many animal species, embryos are exposed to maternal hormones that affect their development. Maternal hormone transfer varies with environmental conditions of the mother and is often interpreted as being shaped by natural selection to adjust the offspring to prevailing environmental conditions. Such hormone transfer requires genetic variability, which has not yet been experimentally demonstrated. Our study reports direct evidence for additive genetic variance of maternal androgens through a bidirectional selection on yolk testosterone (T) levels in Japanese quail. Lines selected for high egg T (HET) and low egg T (LET) concentration differed in yolk levels of this androgen, resulting in high realized heritability (h2 = 0.42)Correlated responses to selection on other gonadal hormones indicated that selection specifically targeted biologically active androgens. Eggs of HET quail contained higher androstenedione and lower estradiol concentrations than did those of LET quail, with no line differences in yolk progesterone concentration. Plasma T concentrations in adult females were not affected by selection, seriously challenging the hypothesis that transfer of maternal hormones to offspring is constrained by hormone levels in a mother's circulation. Our results suggest that transfer of maternal T represents an indirect genetic effect that has important consequences for the evolution of traits in offspring.     

Geographic, demographic and inbreeding patterns in a Basque mountainous region of Guipuzcoa

The Goierri, a mountain region within the Basque Hills of Guipúzcoa, includes one of the most culturally controlled autochthonous populations within the Basque area, mainly from linguistic point of view. The effects of geography and demographic changes (1862–1995) on consanguinity variables over its 21 Municipalities have been investigated. Rates of consanguineous marriages and mean inbreeding levels recorded in some of the southern villages can be considered high but, average values for the entire region were lowered due to the early industrialization of the province. In spite of that, consanguinity in the study area has been, for a long time, a prevailing and conspicuous phenomenon when compared to the other Guipúzcoa regions. The impact of marriages between first cousins from immigrant groups on the regional inbreeding levels represents an interesting result as well. Geographic and demographic factors seem to be related both to the extent of marriages as well as to the number of potential mates within populations, which, in turn, are associated with mean inbreeding levels. Altitude seems to show weak relationship with population distribution and population consanguinity variables. Nevertheless, levels of endogamy appear positively correlated with consanguinity rates and mean inbreeding coefficient and, inversely related-but not statistically significant- to mean village sizes. First cousin marriages yield the highest levels of exogamy and exogamous M22 marriages were mostly concentrated within short (1–10 km) and long-range marital distances (>50 km). The aveaage values of Goierri have been compared with a consanguinity data set of some selected Spanish mountain populations taken from the literature. One of the main results is that geographic and demographic variables are poorly correlated with the most important inbreeding parameters. However, different clusters of populations can be observed with specific characteristics for each of them, not highly correlated with geography.     

GAPDH gene diversity in spirochetes: a paradigm for genetic promiscuity.

In this study we have determined gap sequences from nine different spirochetes. Phylogenetic analyses of these sequences in the context of all other available eubacterial and a selection of eukaryotic Gap sequences demonstrated that the eubacterial glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene diversity encompasses at least five highly distinct gene families. Within these gene families, spirochetes show an extreme degree of sequence divergence that is probably the result of several lateral gene transfer events between spirochetes and other eubacterial phyla, and early gene duplications in the eubacterial ancestor. A Gap1 sequence from the syphilis spirochete Treponema pallidum has recently been shown to be closely related to GapC sequences from Euglenozoa. Here we demonstrate that several other spirochetal species are part of this cluster, supporting the conclusion that an interkingdom gene transfer from spirochetes to Euglenozoa must have occurred. Furthermore, we provide evidence that the GAPDH genes present in the protists Parabasalia may also be of spirochetal descent.     

The multidrug-resistant PMEN1 pneumococcus is a paradigm for genetic success

Background

Streptococcus pneumoniae, also called the pneumococcus, is a major bacterial pathogen. Since its introduction in the 1940s, penicillin has been the primary treatment for pneumococcal diseases. Penicillin resistance rapidly increased among pneumococci over the past 30 years, and one particular multidrug-resistant clone, PMEN1, became highly prevalent globally. We studied a collection of 426 pneumococci isolated between 1937 and 2007 to better understand the evolution of penicillin resistance within this species.

Results

We discovered that one of the earliest known penicillin-nonsusceptible pneumococci, recovered in 1967 from Australia, was the likely ancestor of PMEN1, since approximately 95% of coding sequences identified within its genome were highly similar to those of PMEN1. The regions of the PMEN1 genome that differed from the ancestor contained genes associated with antibiotic resistance, transmission and virulence. We also revealed that PMEN1 was uniquely promiscuous with its DNA, donating penicillin-resistance genes and sometimes many other genes associated with antibiotic resistance, virulence and cell adherence to many genotypically diverse pneumococci. In particular, we describe two strains in which up to 10% of the PMEN1 genome was acquired in multiple fragments, some as long as 32 kb, distributed around the recipient genomes. This type of directional genetic promiscuity from a single clone to numerous unrelated clones has, to our knowledge, never before been described.

Conclusions

These findings suggest that PMEN1 is a paradigm of genetic success both through its epidemiology and promiscuity. These findings also challenge the existing views about horizontal gene transfer among pneumococci.     

The vasa regulatory region mediates germline expression and maternal transmission of proteins in the malaria mosquito Anopheles gambiae: a versatile tool for genetic control strategies

Background  

Germline specific promoters are an essential component of potential vector control strategies which function by genetic drive, however suitable promoters are not currently available for the main human malaria vector Anopheles gambiae.     

Phototransduction in Drosophila: a paradigm for the genetic dissection of sensory transduction cascades.

A combination of molecular, genetic and physiological studies is providing fundamental insight into the function and regulation of the phototransduction cascade. The availability of Drosophila mutants with defects in visual physiology allows for an in vivo dissection of this complex sensory signal transduction process.     

Farnesyltransferase--new insights into the zinc-coordination sphere paradigm: evidence for a carboxylate-shift mechanism

Despite the enormous interest that has been devoted to the study of farnesyltransferase, many questions concerning its catalytic mechanism remain unanswered. In particular, several doubts exist on the structure of the active-site zinc coordination sphere, more precisely on the nature of the fourth ligand, which is displaced during the catalytic reaction by a peptide thiolate. From available crystallographic structures, and mainly from x-ray absorption fine structure data, two possible alternatives emerge: a tightly zinc-bound water molecule or an almost symmetrical bidentate aspartate residue (Asp-297beta). In this study, high-level theoretical calculations, with different-sized active site models, were used to elucidate this aspect. Our results demonstrate that both coordination alternatives lie in a notably close energetic proximity, even though the bidentate hypothesis has a somewhat lower energy. The Gibbs reaction and activation energies for the mono-bidentate conversion, as well as the structure for the corresponding transition state, were also determined. Globally, these results indicate that at room temperature the mono-bidentate conversion is reversible and very fast, and that probably both states exist in equilibrium, which suggests that a carboxylate-shift mechanism may have a key role in the farnesylation process by assisting the coordination/displacement of ligands to the zinc ion, thereby controlling the enzyme activity. Based on this equilibrium hypothesis, an explanation for the existing contradictions between the crystallographic and x-ray absorption fine structure results is proposed.     

Leprosy: a paradigm for the study of human genetic susceptibility to infectious diseases

Fifty years ago, the first identification of a non Mendelian genetic contribution to the development of a common infectious disease, i.e. the association between malaria and sickle-cell trait, was shown using a supervised approach which tests a limited number of candidate genes selected by hypothesis. Since then, the few genes that were convincingly associated with susceptibility to human infectious diseases were identified following the same strategy. The study of leprosy has contributed to modifying this way of thinking. In the absence of a satisfying experimental model and because of the impossibility to grow the causative agent in vitro, the candidate gene approach has turned out to be of limited interest. Conversely, positional cloning led to the identification of two major genes involved in the control of the disease, establishing for the first time the oligogenic nature of a human genetic contribution to an infectious disease. It is likely that these major results obtained in leprosy and the recent burst of genomic tools will make the genome-wide screening (functional or positional) the main strategy of dissection of the genetic susceptibility to many common infectious diseases.     

The Eker rat: establishing a genetic paradigm linking renal cell carcinoma and uterine leiomyoma

Renal Cell Carcinoma (RCC) and uterine leiomyoma (often referred to as fibroids) are tumors arising from tubular epithelium and myometrial compartments of the kidney and uterus, respectively. These tumors have a very different clinical presentation, with RCC being one of the less common cancers, having a very poor prognosis, and occurring predominantly in men, whereas uterine leiomyoma are the most common tumor of women and are benign. Although they are distinct histologically, with RCC arising from epithelial cells and leiomyoma arising from smooth muscle cells, they share a common embryological origin. Renal tubular epithelial cells arise during nephrogenesis as a result of the mesenchymal-epithelial transition of condensed mesenchyme induced by the developing ureteric bud, and have a shared mesenchymal lineage with smooth muscle cells of the uterus. In addition to a common embryological origin, RCC and leiomyoma have been demonstrated to share a common genetic etiology. The Eker rat model was the first demonstration of a specific genetic linkage between RCC and uterine leiomyoma. Eker rats carry a germline defect in the rat homologue of the tuberous sclerosis complex 2 (TSC-2) tumor suppressor gene and develop spontaneous RCC and uterine leiomyoma with a high frequency. TSC patients are also at risk for RCC, and sporadic human uterine leiomyomas exhibit loss of function of the TSC-2 gene product, tuberin. Individuals with the inherited cancer syndrome hereditary leiomyomatosis and renal cell cancer (HLRCC) that have germline defects in the fumarate hydratase (FH) gene develop papillary RCC and uterine and skin leiomyomas. Benign cutaneous lesions and uterine leiomyoma also arise in German Shepherd dogs with germline mutations in the Birt-Hogg-Dube (BHD) gene, and these animals develop RCC and uterine leiomyoma with a high frequency. Identification of the tumor suppressor genes involved in these diseases, TSC, FH and BHD, and the elucidation of the function of their protein products, tuberin, fumarate hydratase and folliculin, respectively, opens new avenues for understanding the pathogenesis of both RCC and uterine leiomyoma.     

The mechanism of maternal inheritance in Chlamydomonas: Biochemical and genetic studies

Summary The cytoplasmic linkage group of Chlamydomonas shows maternal inheritance, i.e. preferential transmission of cytogenes from the female (m t ⁺) parent and loss of the corresponding male (m t ^–) genome in sexual crosses. The mechanism of this process is postulated to be enzymatic modification of chloroplast DNA of the female to protect it from a restriction enzyme which degrades the chloroplast DNA of the male parent in the zygote soon after fusion. Genetic, biochemical and physical data bearing on this hypothesis are summarized and discussed.This paper is dedicated, with great admiration and affection, to Professor Marcus M. Rhoades, whose enthusiasm and curiosity contributed so much to my own scientific development, whose openness to biochemical and molecular interpretations of genetic data, played an exemplary role in focussing my own approach to research and whose fundamental studies of cytoplasmic inheritance in maize (Rhoades 1933, 1946) were directly responsible for my determination to tackle this difficult and perplexing area of research.     

Y-chromosome analysis in Egypt suggests a genetic regional continuity in Northeastern Africa

The geographic location of Egypt, at the interface between North Africa, the Middle East, and southern Europe, prompted us to investigate the genetic diversity of this population and its relationship with neighboring populations. To assess the extent to which the modern Egyptian population reflects this intermediate geographic position, ten Unique Event Polymorphisms (UEPs), mapping to the nonrecombining portion of the Y chromosome, have been typed in 164 Y chromosomes from three North African populations. The analysis of these binary markers, which define 11 Y-chromosome lineages, were used to determine the haplogroup frequencies in Egyptians, Moroccan Arabs, and Moroccan Berbers and thereby define the Y-chromosome background in these regions. Pairwise comparisons with a set of 15 different populations from neighboring European, North African, and Middle Eastern populations and geographic analysis showed the absence of any significant genetic barrier in the eastern part of the Mediterranean area, suggesting that genetic variation and gene flow in this area follow the "isolation-by-distance" model. These results are in sharp contrast with the observation of a strong north-south genetic barrier in the western Mediterranean basin, defined by the Gibraltar Strait. Thus, the Y-chromosome gene pool in the modern Egyptian population reflects a mixture of European, Middle Eastern, and African characteristics, highlighting the importance of ancient and recent migration waves, followed by gene flow, in the region.     

Seaweed attachment to bedrock: biophysical evidence for a new geophycology paradigm

Seaweeds are amongst the most obvious and ecologically important components of rocky shore communities worldwide but until now little has been known about the processes involved in their attachment. This multidisciplinary study investigated for the first time the interactions between marine macroalgal holdfasts and their underlying substrata, requiring the development of specialized sample preparation techniques to maintain the structural integrity of the holdfast–bedrock interface. Transmitted plane polarized light microscopy, scanning electron microscopy with energy dispersive spectroscopy and structured light illumination microscopy were used in the examination of the interface between Ascophyllum nodosum (Fucales, Heterokontophyta) and crustose red algae Lithothamnion sp. (Corallinales, Rhodophyta) on granite and limestone substrates. The new evidence presented here represents a paradigm shift in the way we view seaweed attachment because results show that the holdfasts exploit the physical characteristics of the rock-forming minerals in order to penetrate the bedrock and thus facilitate the attachment process. Mineral cleavage planes together with intercrystalline and intracrystalline boundaries and fractures provide penetration pathways for the holdfast tissue. This process causes disaggregation of rock-forming minerals to depths <10 mm and therefore assists in the bioerosion of coastal bedrock. It is concluded that seaweeds are able to cause weathering of natural rock and the term 'geophycology' is introduced to describe seaweed–bedrock interactions, including seaweed-induced weathering.