Evolution of the spermadhesin gene family

Spermadhesins belong to a novel family of secretory proteins of the male genital tract. They are major proteins of the seminal plasma and have been found peripherally associated to the sperm surface. So far, they have only been detected in ungulates, specifically in pig, cattle, and horse, respectively. Spermadhesins form a subgroup of the superfamily of proteins with a CUB-domain that has been found in a variety of developmentally regulated proteins. The structure and function of the spermadhesins have been investigated in the pig. They are multifunctional proteins showing a range of ligand-binding abilities, e.g. to carbohydrates, phospholipids, and protease inhibitors, suggesting that they may be involved in different steps of fertilization. We report here the genomic organization of the porcine spermadhesin gene cluster as well as a detailed comparative analysis with respect to other mammalian species. The porcine spermadhesin genes are located on SSC 14q28-q29 in a region syntenic to HSA 10q26. The pig contains five closely linked spermadhesin genes, whereas only two spermadhesin genes are present in the cattle genome. Inactive copies of spermadhesin genes are still detectable in the human, chimp, and dog genome while the corresponding region was lost from the rodent genomes of mouse and rat. Within the pig, the five spermadhesin genes contain both highly diverged and highly conserved regions. Interestingly, the pattern of divergence does not correlate with the position of the exons. Evolutionary analyses suggest that the pattern of diversity is shaped by ancestral variation, recombination, and new mutations.

Mechanisms of rapid sympatric speciation by sex reversal and sexual selection in cichlid fish

Mechanisms of speciation in cichlid fish were investigated by analyzing population genetic models of sexual selection on sex-determining genes associated with color polymorphisms. The models are based on a combination of laboratory experiments and field observations on the ecology, male and female mating behavior, and inheritance of sex-determination and color polymorphisms. The models explain why sex-reversal genes that change males into females tend to be X-linked and associated with novel colors, using the hypothesis of restricted recombination on the sex chromosomes, as suggested by previous theory on the evolution of recombination. The models reveal multiple pathways for rapid sympatric speciation through the origin of novel color morphs with strong assortative mating that incorporate both sex-reversal and suppressor genes. Despite the lack of geographic isolation or ecological differentiation, the new species coexists with the ancestral species either temporarily or indefinitely. These results may help to explain different patterns and rates of speciation among groups of cichlids, in particular the explosive diversification of rock-dwelling haplochromine cichlids.

Can ancient colour polymorphisms explain why some cichlid lineages speciate rapidly under disruptive sexual selection?

It is not sufficiently understood why some lineages of cichlid fishes have proliferated in the Great Lakes of East Africa much more than anywhere else in the world, and much faster than other cichlid lineages or any other group of freshwater fish. Recent field and experimental work on Lake Victoria haplochromines suggests that mate choice-mediated disruptive sexual selection on coloration, that can cause speciation even in the absence of geographical isolation, may explain it. We summarize the evidence and propose a hypothesis for the genetics of coloration that may help understand the phenomenon. By detl ning colour patterns by hue and arrangement of hues on the body, we could assign almost all observed phenotypes of Lake Victoria cichlids to one of three female («plain», «orange blotched», «black and white») and three male («blue», «red-ventrum», «reddorsum») colour patterns. These patterns diagnose species but frequently eo-occur also as morphs within the same population, where they are associated with variation in mate preferences, and appear to be transient stages in speciation. Particularly the male patterns occur in almost every genus of the species flock. We propose that the patterns and their association into polymorphisms express an ancestral trait that is retained across speciation. Our model for male colour pattern assumes two structural loci. When both are switched off, the body is blue. When switched on by a cascade of polymorphic regulatory genes, one expresses a yellow to red ventrum, the other one a yellow to red dorsum. The expression of colour variation initiates speciation. The blue daughter species will inherit the variation at the regulatory genes that can, without new mutational events, purely by recombination, again expose the colour polymorphism, starting the process anew. Very similar colour patterns also dominate among the Mbuna of Lake Malawi. In contrast, similar colour polymorphisms do not exist in the lineages that have not proliferated in the Great Lakes. The colour pattern polymorphism may be an ancient trait in the lineage (or lineages) that gave rise to the two large haplochromine radiations. We propose two tests of our hypothesis.

Global diversity, population stratification and selection of human copy number variation

In order to explore the diversity and selective signatures of duplication and deletion human copy number variants (CNVs), we sequenced 236 individuals from 125 distinct human populations. We observed that duplications exhibit fundamentally different population genetic and selective signatures than deletions and are more likely to be stratified between human populations. Through reconstruction of the ancestral human genome, we identify megabases of DNA lost in different human lineages and pinpoint large duplications that introgressed from the extinct Denisova lineage now found at high frequency exclusively in Oceanic populations. We find that the proportion of CNV base pairs to single nucleotide variant base pairs is greater among non-Africans than it is among African populations, but we conclude that this difference is likely due to unique aspects of non-African population history as opposed to differences in CNV load.

A transposable element insertion in APOB causes cholesterol deficiency in Holstein cattle

Cholesterol deficiency, a new autosomal recessive inherited genetic defect in Holstein cattle, has been recently reported to have an influence on the rearing success of calves. The affected animals show unresponsive diarrhea accompanied by hypocholesterolemia and usually die within the first weeks or months of life. Here, we show that whole genome sequencing combined with the knowledge about the pedigree and inbreeding status of a livestock population facilitates the identification of the causative mutation. We resequenced the entire genomes of an affected calf and a healthy partially inbred male carrying one copy of the critical 2.24-Mb chromosome 11 segment in its ancestral state and one copy of the same segment with the cholesterol deficiency mutation. We detected a single structural variant, homozygous in the affected case and heterozygous in the non-affected carrier male. The genetic makeup of this key animal provides extremely strong support for the causality of this mutation. The mutation represents a 1.3kb insertion of a transposable LTR element (ERV2-1) in the coding sequence of the APOB gene, which leads to truncated transcripts and aberrant splicing. This finding was further supported by RNA sequencing of the liver transcriptome of an affected calf. The encoded apolipoprotein B is an essential apolipoprotein on chylomicrons and low-density lipoproteins, and therefore, the mutation represents a loss of function mutation similar to autosomal recessive inherited familial hypobetalipoproteinemia-1 (FHBL1) in humans. Our findings provide a direct gene test to improve selection against this deleterious mutation in Holstein cattle.

DNA-based analysis of protein variants reveals different genetic variability of the paralogous equine ß-lactoglobulin genes LGB1 and LGB2

The genetic variability of milk protein genes may influence the nutritive value or processing and functional properties of the milk. While numerous protein variants are known in ruminants, knowledge about milk protein variability in horses is still limited. Mare's milk is, however, produced for human consumption in many countries. Beta-lactoglobulin belonging to the protein family of lipocalins, which are known as common food- and airborne allergens, is a major whey protein. It is absent from human milk and thus a key agent in provoking cow's milk protein allergy. Mare's milk is, however, usually better tolerated by most affected people. Several functions of β-lactoglobulin have been discussed, but its ultimate physiological role remains unclear. In the current study, the open reading frames of the two equine β-lactoglobulin paralogues LGB1 and LGB2 were re-sequenced in 249 horses belonging to 14 different breeds in order to predict the existence of protein variants at the DNA-level. Thereby, only a single signal peptide variant of LGB1, but 10 different putative protein variants of LGB2 were identified. In horses, both genes are expressed and in such this is a striking previously unknown difference in genetic variability between the two genes. It can be assumed that LGB1 is the ancestral paralogue, which has an essential function causing a high selection pressure. As horses have very low milk fat content this unknown function might well be related to vitamin-uptake. Further studies are, however, needed, to elucidate the properties of the different gene products.

Genetic mechanisms of Na+, K+-ATPase regulation in hypertension

The spontaneously hypertensive rat (SHR) is a model of essential hypertension. During the early development of hypertension, the SHR demonstrates increased proximal tubule (PT) Na+ reabsorption. I hypothesized that the increased PT Na+ reabsorption exhibited by the young SHR was due to altered sub-cellular distribution of Na+, K +-ATPase compared to the normotensive Wistar Kyoto (WKY). The hypothesis is supported, herein, by observations of greater Na+, K +-ATPase α 1 abundance in PT plasma membrane and lower abundance in late endosomes of 4wk SHR despite no difference in total PT α 1 abundance. There is a greater amount of Ser-18 unphosphorylated α 1 in the 4wk SHR PT. Total PT Na+, K+-ATPase γ abundance is greater in SHR at 4wk and 16wk but γ abundance in plasma membrane is greater only at 4wk. The phosphatase, calcineurin, was chosen for study because it is involved in the stimulation of Na+, K +-ATPase. No difference in calcineurin coding sequence, expression, or activity was observed in SHR. Gene expression arrays were next used to find candidate genes involved in the regulation of Na+, K +-ATPase. The first candidate analyzed was soluble epoxide hydrolase (sEH). The gene encoding sEH (EPHX2) showed lower expression in SHR. There was also a reduction in sEH protein abundance but there was no correlation between protein abundance and blood pressure in F2 progeny. Two EPHX2 alleles were identified, an ancestral allele and a variant allele containing four polymorphisms. sEH activity was greater in animals carrying the variant allele but the inheritance of the variant allele did not correlate with blood pressure. Gene expression arrays also led to the examination of genes involved in redox balance/Na+, K+-ATPase regulation. A pattern of lower expression of genes involved in reactive radical detoxification in SHR was discerned. Six transcription factor binding sites were identified that occurred more often in these genes. Three transcription factors that bind to the HNF1 site were expressed at lower levels in SHR. This points to the HNF1 transcriptional complex as an important trans-acting regulator of a wide range of genes involved in altered redox balance in SHR. ^

IDENTIFYING GENETIC VARIANTS AND CHARACTERIZING THEIR ROLE IN CLUBFOOT

Clubfoot is a common, complex birth defect affecting 4,000 newborns in the United States and 135,000 world-wide each year. The clubfoot deformity is characterized by inward and rigid downward displacement of one or both feet, along with persistent calf muscle hypoplasia. Despite strong evidence for a genetic liability, there is a limited understanding of the genetic and environmental factors contributing to the etiology of clubfoot. The studies described in this dissertation were performed to identify variants and/or genes associated with clubfoot. Genome-wide linkage scan performed on ten multiplex clubfoot families identified seven new chromosomal regions that provide new areas to search for clubfoot genes. Troponin C (TNNC2) the strongest candidate gene, located in 20q12-q13.11, is involved in muscle contraction. Exon sequencing of TNNC2 did not identify any novel coding variants. Interrogation of fifteen muscle contraction genes found strong associations with SNPs located in potential regulatory regions of TPM1 (rs4075583 and rs3805965), TPM2 (rs2025126 and rs2145925) and TNNC2 (rs383112 and rs437122). In previous studies, a strong association was found with rs3801776 located in the basal promoter of HOXA9, a gene also involved in muscle development and patterning. Altogether, this data suggests that SNPs located in potential regulatory regions of genes involved in muscle development and function could alter transcription factor binding leading to changes in gene expression. Functional analysis of 3801776/HOXA9, rs2025126/TPM2 and rs2145925/TPM2 showed altered protein binding, which significantly influenced promoter activity. Although the ancestral allele (G) of rs4075583/TPM1 creates a DNA-protein complex, it did not affect TPM1 promoter activity. However and importantly, in the context of a haplotype, rs4075583/G significantly decreased TPM1 promoter activity. These results suggest dysregulation of multiple skeletal muscle genes, TPM1, TPM2, TNNC2 and HOXA9, working in concert may contribute to clubfoot. However, specific allelic combinations involving these four regulatory SNPs did not confer a significantly higher risk for clubfoot. Other combinations of these variants are being evaluated. Moreover, these variants may interact with yet to be discovered variants in other genes to confer a higher clubfoot risk. Collectively, we show novel evidence for the role of skeletal muscle genes in clubfoot indicating that there are multiple genetic factors contributing to this complex birth defect.

Mineralogy and age determination of sediment core D11957P

The Tore Seamount is a circular, volcano-like feature 100 km in diameter with its summit at 2200 m water depth and a small, 5000 m deep basin in its interior. It is situated approximately 300 km west of Lisbon and is surrounded by deep abyssal plains. This site with a standard pelagic stratigraphy is the southernmost point where the so-called Heinrich events have so far been recorded. A succession of alternating interglacial/glacial periods reveals a stratigraphic record back to the beginning of isotopic stage 7 (225 kyr). Climatic changes are identifiable by coherent variations in colour, carbonate content and distribution of ice-rafted detritus in the carbonate-free fraction. Inputs of ice-rafted quartz are well defined. Characteristics in common with other sites showing Heinrich layers include a high terrigenous to biogenic ratio, a dramatic decrease in the accumulation rate of foraminifera shells, an increase in dolomite abundance and the occurrence of polar foraminiferal species indicating southwards penetration of cold waters which lead us to consider a wider southeastern extent of the North Atlantic ice-rafted detritus belt than hitherto. If the presently accepted position of the Polar Front is maintained, icebergs must have been swept southwards from the southern boundary of the pack ice in a current merging into the ancestral Canary Current, bringing ice-rafted material to the Tore Seamount. The coincidence of reddish-feldspar, probably derived from the northern Appalachian Triassic red facies, with the transparent quartz suggests at least a partial Labrador source for all the Heinrich layers here, including HL 3. In comparison to other sites in the entire North Atlantic, two exceptions stand out: the absence of HL 5 and the low detritus to biogenics ratio for HL 3. The simultaneous occurrence of these two types of ice-rafted minerals is a new piece in the puzzle of the origin of Heinrich layers.

Isotope ratios and trace element concentrations of basalts from DSDP Leg 15 sites (Appendix 1)

Formation of the Cretaceous Caribbean plateau, including the komatiites of Gorgona, has been linked to the currently active Galápagos hotspot. We use Hf-Nd isotopes and trace element data to characterise both the Caribbean plateau and the Galápagos hotspot, and to investigate the relationship between them. Four geochemical components are identified in the Galápagos mantle plume: two 'enriched' components with epsilon-Hf and epsilon-Nd similar to enriched components observed in other mantle plumes, one moderately enriched component with high Nb/Y, and a fourth component which most likely represents depleted MORB source mantle. The Caribbean plateau basalt data form a linear array in Hf-Nd isotope space, consistent with mixing between two mantle components. Combined Hf-Nd-Pb-Sr-He isotope and trace element data from this study and the literature suggest that the more enriched Caribbean end member corresponds to one or both of the enriched components identified on Galápagos. Likewise, the depleted end member of the array is geochemically indistinguishable from MORB and corresponds to the depleted component of the Galápagos system. Enriched basalts from Gorgona partially overlap with the Caribbean plateau array in epsilon-Hf vs. epsilon-Nd, whereas depleted basalts, picrites and komatiites from Gorgona have a high epsilon-Hf for a given epsilon-Nd, defining a high-epsilon-Hf depleted end member that is not observed elsewhere within the Caribbean plateau sequences. This component is similar, however, in terms of Hf-Nd-Pb-He isotopes and trace elements to the depleted plume component recognised in basalts from Iceland and along the Reykjanes Ridge. We suggest that the Caribbean plateau represents the initial outpourings of the ancestral Galápagos plume. Absence of a moderately enriched, high Nb/Y component in the older Caribbean plateau (but found today on the island of Floreana) is either due to changing source compositions of the plume over its 90 Ma history, or is an artifact of limited sampling. The high-epsilon-Hf depleted component sampled by the Gorgona komatiites and depleted basalts is unique to Gorgona and is not found in the Caribbean plateau. This may be an indication of the scale of heterogeneity of the Caribbean plateau system; alternatively Gorgona may represent a separate oceanic plateau derived from a completely different Pacific plume, such as the Sala y Gomez.

¿El vudú haitiano es un humanismo?

Este estudio se propone explicar el Vudú, esa religión mal conocida, desprestigiada, tergiversada por las revistas, los libros, las películas que se dicen serias y objetivas. De manera sistemática y con gran sensacionalismo, los medios extranjeros han contribuido a presentarla constantemente como una horrible acumulación de groseras supersticiones, orgías sexuales, magia negra, brujería y maleficios. Sin embargo, el Vudú haitiano no es sólo una religión recreada por los esclavos africanos en la colonia francesa de Santo Domingo, es por el contrario un Humanismo, un conjunto de tradiciones culturales que constituyen el cimiento que une al pueblo haitiano en los momentos de crisis y lo salva de la desesperanza. Gracias al Vudú, ciertos valores morales que se pierden en otros pueblos considerados "avanzados y civilizados" se encuentran todavía ligados a una red que condiciona todos los actos de la vida cotidiana de los haitianos de cualquier clase social a la que pertenezcan. Se presentan aquí los puntos clave de la filosofía vudú y su modo de transferencia de una generación a otra. De igual modo, el arte y la pintura de Haití, inspirados por el culto ancestral, han sorprendido al mundo por su vitalidad, su creatividad y su humanismo.

Lectura intercultural de 'Los días del venado' de Liliana Bodoc

La cultura clásica, en especial la griega, a menudo y sostenidamente ha atraído a escritores mendocinos de cuna o por adopción. En ese marco, el presente trabajo explora primero rasgos de la épica helénica y luego analiza elementos de la cultura americana precolombina, en el tratamiento de personajes, intervención divina, sucesos, espacio y tiempo en Los días del venado, obra reconocida con el primer premio de la Fundación "El Libro" a la mejor publicación juvenil de 2000. Hipótesis de trabajo: En Los días del venado se concentran dos vertientes ancestrales en tensión, la helena y la americanista indígena. Esta última predomina en la toma de posición ideológica de la historia narrada. Método: Análisis de contenido sin categorías fijadas a priori, por cuanto se trata de una metodología fenomenológíca y cualitativa. Resultados previstos: aporte para la comprensión crítica, con una lectura reflexiva de doble vía de la novela: el reconocimiento de la herencia helena (helenos, en efectos, son los nombres de los vasallos de Misáianes que invaden las Tierras Fértiles) más una importante cosmovisión americanista -en especial maya y araucana-, que la diferencia notablemente de las cualidades eurocéntricas de una saga al estilo de J. R. R. Tolkien.

Direcciones del vanguardismo hispanoamericano : estudios sobre poesía de vanguardia : 1920-1930 : documentos

Una ya clásica contribución al estudio del vanguardismo literario hispanoamericano. La obra de Gloria Videla de Rivero recopila ensayos de su autoría sobre la poesía de vanguardia de la década del 20, así como manifiestos y textos programáticos de los principales poetas y teóricos del vanguardismo: Huidobro, Borges, Vallejo, Mariátegui, entre otros. Con la hipótesis de que la avidez cosmopolita y universalista de los hispanoamericanos se mestiza con la fuerte impronta de los caracteres locales (nativismo o criollismo, negrismo, indigenismo), la autora indaga, con arraigado sentido de pertenencia, en el giro americano del fenómeno y explora también otro rasgo ancestral de esta literatura: la búsqueda de soluciones a los problemas sociales por el camino poético. Esta tercera edición de DIRECCIONES DEL VANGUARDISMO HISPANOAMERICANO: ESTUDIOS SOBRE POESÍA DE VANGUARDIA: 1920-1930. DOCUMENTOS realiza varias incorporaciones, de especial interés para investigadores e interesados en el tema, como un completo índice alfabético de nombres y un anexo con imágenes de publicaciones vanguardistas.

The Fohsella chronocline in middle Miocene sediments from the Ontong Java Plateau, Pacific Ocean

Micropaleontologists have traditionally recognized the mid-Miocene Fohsella lineage as a flagship for phyletic gradualism within the planktic foraminifera. However, study of a deep-sea record from the western equatorial Pacific (ODP Site 806) reveals that coiling ratios within this clade suddenly (<5 kyr) shift after a prolonged, ancestral state of near randomness (~50%) to a transient phase (13.42-13.43 Ma) of dextral dominance (~75%) immediately following the first common occurrence of keeled fohsellids. This brief period of dextral dominance was abruptly (<5 kyr) succeeded by an irreversible change to sinistral dominance (~96%). Fohsellid abundances decline markedly through the interval in which the sinistral preference is established. The shift to sinistrality (13.42 Ma) predated the deepening of fohsellid depth ecology by ~240-488 kyr, indicating that these two events were unrelated. This view is supported by a lack of delta 18O evidence for depth-habitat differences between the two chiral forms, which refutes the notion that sinistral fohsellids were "pre-adapted" for ensuing hydrographic change because they occupied a deeper depth habitat than their dextral counterparts. Planktic foraminiferal assemblages become strongly oligotrophic in character through the interval in which the fohsellid delta 18O increase is recorded, indicating that the migration to deeper depths was fostered by an expansion of the mixed layer in the western equatorial Pacific. Salient aspects of this brief, but conspicuous faunal change are a marked increase in the abundance of symbiont-bearing globigerinoidids, a concomitant collapse of local Jenkinsella mayeri/siakensis populations, and reduced fohsellid abundances. The rapid and permanent nature of the Fohsella sinistral shift provides a distinct, unequivocal datum that may prove useful for correlating mid-Miocene sections throughout the Caribbean Sea and tropical regions in the western sectors of the Pacific and Atlantic. The coiling ratio changes that occurred during the evolution of the Fohsella chronocline probably reflect changing population dynamics between cryptic genotypes with different coiling preferences.