Genetic evidence for the Mongolian ancestry of Kalmyks

The Kalmyks are an ethnic group along the lower Volga River in Russia who are thought to have migrated there from Mongolia about 300 years ago. To investigate their origins, we studied mtDNA and Y-chromosome variation in 99 Kalmyks. Both mtDNA HV1 sequences and Y-chromosome SNP haplogroups indicate a close relationship of Kalmyks with Mongolians. In addition, genetic diversity for both mtDNA and the Y chromosome are comparable in Kalmyks, Mongolians, and other Central Asian groups, indicating that the Kalmyk migration was not associated with a substantial bottleneck. The so-called "Genghis Khan" Y-chromosome short tandem repeat (STR) haplotype was found in high frequency (31.3%) among Kalmyks, further supporting a strong genetic connection between Kalmyks and Mongolians. Genetic analyses of even recent, relatively well-documented migrations such as of the Kalmyks can therefore lead to new insights concerning such migrations.     

Ontogenetic evidence for the Paleozoic ancestry of salamanders

The phylogenetic positions of frogs, salamanders, and caecilians have been difficult to establish. Data matrices based primarily on Paleozoic taxa support a monophyletic origin of all Lissamphibia but have resulted in widely divergent hypotheses of the nature of their common ancestor. Analysis that concentrates on the character states of the stem taxa of the extant orders, in contrast, suggests a polyphyletic origin from divergent Paleozoic clades. Comparison of patterns of larval development in Paleozoic and modern amphibians provides a means to test previous phylogenies based primarily on adult characteristics. This proves to be highly informative in the case of the origin of salamanders. Putative ancestors of salamanders are recognized from the Permo-Carboniferous boundary of Germany on the basis of ontogenetic changes observed in fossil remains of larval growth series. The entire developmental sequence from hatching to metamorphosis is revealed in an assemblage of over 600 specimens from a single locality, all belonging to the genus Apateon. Apateon forms the most speciose genus of the neotenic temnospondyl family Branchiosauridae. The sequence of ossification of individual bones and the changing configuration of the skull closely parallel those observed in the development of primitive living salamanders. These fossils provide a model of how derived features of the salamander skull may have evolved in the context of feeding specializations that appeared in early larval stages of members of the Branchiosauridae. Larvae of Apateon share many unique derived characters with salamanders of the families Hynobiidae, Salamandridae, and Ambystomatidae, which have not been recognized in any other group of Paleozoic amphibians.     

Statistical evidence for common ancestry: Application to primates

Since Darwin, biologists have come to recognize that the theory of descent from common ancestry (CA) is very well supported by diverse lines of evidence. However, while the qualitative evidence is overwhelming, we also need formal methods for quantifying the evidential support for CA over the alternative hypothesis of separate ancestry (SA). In this article, we explore a diversity of statistical methods using data from the primates. We focus on two alternatives to CA, species SA (the separate origin of each named species) and family SA (the separate origin of each family). We implemented statistical tests based on morphological, molecular, and biogeographic data and developed two new methods: one that tests for phylogenetic autocorrelation while correcting for variation due to confounding ecological traits and a method for examining whether fossil taxa have fewer derived differences than living taxa. We overwhelmingly rejected both species and family SA with infinitesimal P values. We compare these results with those from two companion papers, which also found tremendously strong support for the CA of all primates, and discuss future directions and general philosophical issues that pertain to statistical testing of historical hypotheses such as CA.     

Genetic ancestry and indigenous heritage in a Native American descendant community in Bermuda

Discovered in the early 16th century by European colonists, Bermuda is an isolated set of islands located in the mid-Atlantic. Shortly after its discovery, Bermuda became the first English colony to forcibly import its labor by trafficking in enslaved Africans, white ethnic minorities, and indigenous Americans. Oral traditions circulating today among contemporary tribes from the northeastern United States recount these same events, while, in Bermuda, St. David's Islanders consider their histories to be linked to a complex Native American, European, and African past. To investigate the influence of historical events on biological ancestry and native cultural identity, we analyzed genetic variation in 111 members of Bermuda's self-proclaimed St. David's Island Native Community. Our results reveal that the majority of mitochondrial DNA (mtDNA) and Y-chromosome haplotypes are of African and West Eurasian origin. However, unlike other English-speaking New World colonies, most African mtDNA haplotypes appear to derive from central and southeast Africa, reflecting the extent of maritime activities in the region. In light of genealogical and oral historical data from the St. David's community, the low frequency of Native American mtDNA and NRY lineages may reflect the influence of genetic drift, the demographic impact of European colonization, and historical admixture with persons of non-native backgrounds, which began with the settlement of the islands. By comparing the genetic data with genealogical and historical information, we are able to reconstruct the complex history of this Bermudian community, which is unique among New World populations.     

Further evidence for changes in the level of palmitoyl-CoA desaturase during thermal adaptation in Tetrahymena pyriformis

Palmitoyl-CoA desaturase activity in microsomes was increased up to about 4-fold within 2 h after temperature shift from 39.5 to 15°C. Compared with control cells, cycloheximide-treated cells indicated no induction of palmitoyl-CoA desaturase by a decrease in temperature. The results suggest that temperature acclimation requires an increase in the level of the desaturase enzyme content.     

Identification of a multidrug resistance-like system in Tetrahymena pyriformis: evidence for a new detoxication mechanism in freshwater ciliates.

The freshwater ciliate Tetrahymena pyriformis is an ubiquitous organism that is present in all aquatic ecosystems. This protozoan showed a clear resistance against some polycyclic aromatic hydrocarbons which can be attributed to an efflux pump probably of the multidrug resistance (MDR) type. Immunocytochemical detection showed a positive stain of ciliate cells using the monoclonal antibodies 4E3, raised against P-glycoprotein (P-gp). The kinetics of P-gp expression were studied for control cultures and cultures treated with 15 microM benzo(a)pyrene. Western blot analysis using the Ab1, anti-P-gp polyclonal antibodies indicates the presence of two bands of 66 and 96 kDa of which the intensity increased with time in benzo(a)pyrene-treated ciliates. Uptake experiments with target compounds for the MDR pump, namely adriamycin, rhodamine 123 and two polycyclic aromatic hydrocarbons, benzo(a)pyrene and 7,12-dimethylbenzanthracene, were carried out by flow cytometry, in the presence or absence of cyclosporin (an inhibitor of the multidrug resistant pump). The data indicate that the accumulation of these compounds by ciliate cells is significantly enhanced in the presence of cyclosporin. This suggests that Tetrahymena is provided with a P-gp-like system that is functionally active in a way similar to that of the mammalian P-gp.     

Genetic ancestry,admixture and health determinants in Latin America

Background

Modern Latin American populations were formed via genetic admixture among ancestral source populations from Africa, the Americas and Europe. We are interested in studying how combinations of genetic ancestry in admixed Latin American populations may impact genomic determinants of health and disease. For this study, we characterized the impact of ancestry and admixture on genetic variants that underlie health- and disease-related phenotypes in population genomic samples from Colombia, Mexico, Peru, and Puerto Rico.

Results

We analyzed a total of 347 admixed Latin American genomes along with 1102 putative ancestral source genomes from Africans, Europeans, and Native Americans. We characterized the genetic ancestry, relatedness, and admixture patterns for each of the admixed Latin American genomes, finding a spectrum of ancestry proportions within and between populations. We then identified single nucleotide polymorphisms (SNPs) with anomalous ancestry-enrichment patterns, i.e. SNPs that exist in any given Latin American population at a higher frequency than expected based on the population’s genetic ancestry profile. For this set of ancestry-enriched SNPs, we inspected their phenotypic impact on disease, metabolism, and the immune system. All four of the Latin American populations show ancestry-enrichment for a number of shared pathways, yielding evidence of similar selection pressures on these populations during their evolution. For example, all four populations show ancestry-enriched SNPs in multiple genes from immune system pathways, such as the cytokine receptor interaction, T cell receptor signaling, and antigen presentation pathways. We also found SNPs with excess African or European ancestry that are associated with ancestry-specific gene expression patterns and play crucial roles in the immune system and infectious disease responses. Genes from both the innate and adaptive immune system were found to be regulated by ancestry-enriched SNPs with population-specific regulatory effects.

Conclusions

Ancestry-enriched SNPs in Latin American populations have a substantial effect on health- and disease-related phenotypes. The concordant impact observed for same phenotypes across populations points to a process of adaptive introgression, whereby ancestry-enriched SNPs with specific functional utility appear to have been retained in modern populations by virtue of their effects on health and fitness.

     

Photolysis in a culture medium for Tetrahymena pyriformis

Considerable variability has been found in the yield of cells in batch cultures of Tetrahymena pyriformis grown axenically in 1% tryptone/0.05% yeast extract. This variability has been traced to the photolysis by visible light of the flavin mononucleotide and thiamine components of yeast extract.     

Molecular phylogenetic evidence that the phylum Haplosporidia has an alveolate ancestry

The phylogenetic position of the phylum Haplosporidia among other protists was investigated with the complete 16S-like rRNA gene sequences from two species in the phylum: Haplosporidium nelsoni, a parasite of oysters, and Minchinia teredinis, a parasite of shipworms. Because the lack of obvious morphological homologies with other protists hampered decisions regarding taxonomic composition for sequence alignment and phylogenetic analysis, the complete sequences for these two haplosporidians were directed as search queries to the blast/ncbi.nlm.nih.gov electronic mail server. The results of this heuristic similarity search provided a basis for constructing a preliminary higher-taxonomic-level analysis comparing the haplosporidians with species from the slime molds, fungi, algae, amoebae, ciliates, dinoflagellates, and apicomplexans. Maximum parsimony yielded equivocal results, whereas transversionally weighted parsimony suggested an affinity with the alveolates (i.e., the ciliates, dinoflagellates, and apicomplexans). Multiple alignment of the two haplosporidian sequences against 17 taxa in a secondary analysis focusing on the alveolates and subsequent parsimony analysis placed the phylum Haplosporidia as a monophyletic group within the Alveolata and as a taxon of equal rank with the other three alveolate phyla. The precise placement within the Alveolata was sensitive to weighting.      

Further evidence for changes in the level of palmitoyl-CoA desaturase during thermal adaptation in Tetrahymena pyriformis.

Palmitoyl-CoA desaturase activity in microsomes was increased up to about 4-fold within 2 h after temperature shift from 39.5 to 15 degrees C. Compared with control cells, cycloheximide-treated cells indicated no induction of palmitoyl-CoA desaturase by a decrease in temperature. The results suggest that temperature acclimation requires an increase in the level of the desaturase enzyme content.     

Genetic evidence for a neurovestibular influence on the mammalian circadian pacemaker

The mammalian circadian timing system (CTS) exerts endogenous temporal control over virtually every biochemical, physiological, and neurobiological process. Recent studies have suggested an interrelationship between the neurovestibular system, specifically the macular otoconial gravity receptors, and the CTS. To test for a functional relationship between these 2 seemingly disparate neuronal systems, the authors performed a study to evaluate the influence of the vestibular system on 3 fundamental properties of the CTS: entrainment, photic modulation, and period. The present study used a nonrecombinant mutant mouse, the head-tilt mouse (abbr. het), which lacks otoconia and hence gravity reception, to evaluate CTS function in mice lacking vestibular inputs. Circadian rhythms of body temperature (Tb) and locomotor activity (ACT) were recorded continuously by biotelemetry in het mice as well as wild-type (PWT) controls during exposure to 4 photic regimens: 12:12 LD, DD (0 micromoles s(-1) m(-2)), constant bright light (LL(B); 0.5 micromoles s(-1) m(-2)), and constant dim light (LL(D); 0.02 micromoles s(-1) m(-2)). In DD, the circadian period of the Tb and ACT rhythms was significantly longer (p < 0.001) in het than in PWT mice. In addition, the circadian period of Tb and ACT was significantly longer (p < 0.01) in LL(B) than in DD for both the het and PWT groups, although increasing ambient illuminance (i.e., DD to LL(B)) had a significantly greater (p < 0.01) period-lengthening effect in the PWT group than in the het group. The results of the present study demonstrate for the first time that the vestibular macular gravity receptors influence 2 fundamental properties of the mammalian CTS: (1) the intrinsic circadian pacemaker period and (2) the period-altering response to changes in tonic light intensity. The results of the present study thus provide the first neurobehavioral evidence for a vestibular-circadian interrelationship as well as suggest a novel mechanism underlying the signaling of activity-based nonphotic stimuli to the CTS.     

Genetic evidence for a defective xylan degradation pathway in Lactococcus lactis

Genetic and biochemical evidence for a defective xylan degradation pathway was found linked to the xylose operon in three lactococcal strains, Lactococcus lactis 210, L. lactis IO-1, and L. lactis NRRL B-4449. Immediately downstream of the xylulose kinase gene (xylB) (K. A. Erlandson, J.-H. Park, W. El Khal, H.-H. Kao, P. Basaran, S. Brydges, and C. A. Batt, Appl. Environ. Microbiol. 66:3974-3980, 1999) are two open reading frames encoding a mutarotase (xylM) and a xyloside transporter (xynT) and a partial open reading frame encoding a beta-xylosidase (xynB). These are functions previously unreported for lactococci or lactobacilli. The mutarotase activity of the putative xylM gene product was confirmed by overexpression of the L. lactis enzyme in Escherichia coli and purification of recombinant XylM. We hypothesize that the mutarotase links xylan degradation to xylose metabolism due to the anomeric preference of xylose isomerase. In addition, Northern hybridization experiments suggested that the xylM and xynTB genes are cotranscribed with the xylRAB genes, responsible for xylose metabolism. Although none of the three strains appeared to metabolize xylan or xylobiose, they exhibited xylosidase activity, and L. lactis IO-1 and L. lactis NRRL B-4449 had functional mutarotases.     

New sequence motifs in flavoproteins: evidence for common ancestry and tools to predict structure

We describe two new sequence motifs, present in several families of flavoproteins. The "GG motif" (RxGGRxxS/T) is found shortly after the betaalphabetadinucleotide-binding motif (DBM) in L-amino acid oxidases, achacin and aplysianin-A, monoamine oxidases, corticosteroid-binding proteins, and tryptophan 2-monooxygenases. Other disperse sequence similarities between these families suggest a common origin. A GG motif is also found in protoporphyrinogen oxidase and carotenoid desaturases and, reduced to the central GG doublet, in the THI4 protein, dTDP-4-dehydrorhamnose reductase, soluble fumarate reductase, steroid dehydrogenases, Rab GDP-dissociation inhibitor, and in most flavoproteins with two dinucleotide-binding domains (glutathione reductase, glutamate synthase, flavin-containing monooxygenase, trimethylamine dehydrogenase...). In the latter families, an "ATG motif" (oxhhhATG) is found in both the FAD- and NAD(P)H-binding domains, forming the fourth beta-strand of the Rossman fold and the connecting loop. On the basis of these and previously described motifs, we present a classification of dinucleotide-binding proteins that could also serve as an evolutionary scheme. Like the DBM, the ATG motif appears to predate the divergence of NAD(P)H- and FAD-binding proteins. We propose that flavoproteins have evolved from a well-differentiated NAD(P)H-binding protein. The bulk of the substrate-binding domain was formed by an insertion after the fourth beta-strand, either of a closely related NAD(P)H-binding domain or of a domain of completely different origin.