Detecting ancient positive selection in humans using extended lineage sorting

Natural selection that affected modern humans early in their evolution has likely shaped some of the traits that set present-day humans apart from their closest extinct and living relatives. The ability to detect ancient natural selection in the human genome could provide insights into the molecular basis for these human-specific traits. Here, we introduce a method for detecting ancient selective sweeps by scanning for extended genomic regions where our closest extinct relatives, Neandertals and Denisovans, fall outside of the present-day human variation. Regions that are unusually long indicate the presence of lineages that reached fixation in the human population faster than expected under neutral evolution. Using simulations we show that the method is able to detect ancient events of positive selection and that it can differentiate those from background selection. Applying our method to the 1000 genomes dataset, we find evidence for ancient selective sweeps favoring regulatory changes in the brain and present a list of genomic regions that are predicted to underlie positively selected human specific traits

ABAEnrichment: An R package to test for gene set expression enrichment in the adult and developing human brain

Summary: We present ABAEnrichment, an R package that tests for expression enrichment in specific brain regions at different developmental stages using expression information gathered from multiple regions of the adult and developing human brain, together with ontologically organized structural information about the brain, both provided by the Allen Brain Atlas. We validate ABAEnrichment by successfully recovering the origin of gene sets identified in specific brain cell-types and developmental stages. Availability and Implementation: ABAEnrichment was implemented as an R package and is available under GPL (≥ 2) from the Bioconductor website (http://bioconductor.org/packages/3.3/bioc/html/ABAEnrichment.html). Contacts: [email protected], [email protected] or [email protected] Supplementary information: Supplementary data are available at Bioinformatics online

Computational challenges in the analysis of ancient DNA

High-throughput sequencing technologies have opened up a new avenue for studying extinct organisms. Here we identify and quantify biases introduced by particular characteristics of ancient DNA samples. These analyses demonstrate the importance of closely related genomic sequence for correctly identifying and classifying bona fide endogenous DNA fragments. We show that more accurate genome divergence estimates from ancient DNA sequence can be attained using at least two outgroup genomes and appropriate filtering

Nuclear and mitochondrial DNA sequences from two Denisovan individuals

Denisovans, a sister group of Neandertals, have been described on the basis of a nuclear genome sequence from a finger phalanx (Denisova 3) found in Denisova Cave in the Altai Mountains. The only other Denisovan specimen described to date is a molar (Denisova 4) found at the same site. This tooth carries a mtDNA sequence similar to that of Denisova 3. Here we present nuclear DNA sequences from Denisova 4 and a morphological description, as well as mitochondrial and nuclear DNA sequence data, from another molar (Denisova 8) found in Denisova Cave in 2010. This new molar is similar to Denisova 4 in being very large and lacking traits typical of Neandertals and modern humans. Nuclear DNA sequences from the two molars form a clade with Denisova 3. The mtDNA of Denisova 8 is more diverged and has accumulated fewer substitutions than the mtDNAs of the other two specimens, suggesting Denisovans were present in the region over an extended period. The nuclear DNA sequence diversity among the three Denisovans is comparable to that among six Neandertals, but lower than that among present-day humans

Complex Calogero model with real energies

We show that and how PT symmetry (interpreted as a "weakened Hermiticity") can be extended to the exactly solvable two- and three-particle Calogero model.Comment: 16 pages, 3 figures, submitted to J. Phys.

Multivariate Lagrange inversion formula and the cycle lemma

International audienceWe give a multitype extension of the cycle lemma of (Dvoretzky and Motzkin 1947). This allows us to obtain a combinatorial proof of the multivariate Lagrange inversion formula that generalizes the celebrated proof of (Raney 1963) in the univariate case, and its extension in (Chottin 1981) to the two variable case. Until now, only the alternative approach of (Joyal 1981) and (Labelle 1981) via labelled arborescences and endofunctions had been successfully extended to the multivariate case in (Gessel 1983), (Goulden and Kulkarni 1996), (Bousquet et al. 2003), and the extension of the cycle lemma to more than 2 variables was elusive. The cycle lemma has found a lot of applications in combinatorics, so we expect our multivariate extension to be quite fruitful: as a first application we mention economical linear time exact random sampling for multispecies trees

Overexpression of a pseudo-etiolated-in-light-like protein in Taraxacum koksaghyz leads to a pale green phenotype and enables transcriptome-based network analysis of photomorphogenesis and isoprenoid biosynthesis

IntroductionPlant growth and greening in response to light require the synthesis of photosynthetic pigments such as chlorophylls and carotenoids, which are derived from isoprenoid precursors. In Arabidopsis, the pseudo-etiolated-in-light phenotype is caused by the overexpression of repressor of photosynthetic genes 2 (RPGE2), which regulates chlorophyll synthesis and photosynthetic genes.MethodsWe investigated a homologous protein in the Russian dandelion (Taraxacum koksaghyz) to determine its influence on the rich isoprenoid network in this species, using a combination of in silico analysis, gene overexpression, transcriptomics and metabolic profiling.ResultsHomology-based screening revealed a gene designated pseudo-etiolated-in-light-like (TkPEL-like), and in silico analysis identified a light-responsive G-box element in its promoter. TkPEL-like overexpression in dandelion plants and other systems reduced the levels of chlorophylls and carotenoids, but this was ameliorated by the mutation of one or both conserved cysteine residues. Comparative transcriptomics in dandelions overexpressing TkPEL-like showed that genes responsible for the synthesis of isoprenoid precursors and chlorophyll were downregulated, probably explaining the observed pale green leaf phenotype. In contrast, genes responsible for carotenoid synthesis were upregulated, possibly in response to feedback signaling. The evaluation of additional differentially expressed genes revealed interactions between pathways.DiscussionWe propose that TkPEL-like negatively regulates chlorophyll- and photosynthesis-related genes in a light-dependent manner, which appears to be conserved across species. Our data will inform future studies addressing the regulation of leaf isoprenoid biosynthesis and photomorphogenesis and could be used in future breeding strategies to optimize selected plant isoprenoid profiles and generate suitable plant-based production platforms

The Classical Schrodinger's Equation

A non perturbative numerical method for determining the discrete spectra is deduced from the classical analogue of the Schrodinger's equation. The energy eigenvalues coincide with the bifurcation parameters for the classical orbits.Comment: UUEncoded Postscript, 18 pages, 4 figures inserted in tex

Evaluation of antigens for the serodiagnosis of kala-azar and oriental sores by means of the indirect immunofluorescence antibody test (IFAT)

Antigens and corresponding sera were collected from travellers with leishmaniasis returning to Germany from different endemic areas of the old world. The antigenicity of these Leishmania strains, which were maintained in Syrian hamsters, was compared by indirect immunofluorescence (IFAT). Antigenicity was demonstrated by antibody titres in 18 sera from 11 patients. The amastigotic stages of nine strains of Leishmania donovani and four strains of Leishmania tropica were compared with each other and with the culture forms of insect flagellates (Strigomonas oncopelti and Leptomonas ctenocephali). Eighteen sera from 11 patients were available for antibody determination with these antigens. The maximal antibody titres in a single serum varied considerably depending on which antigen was used for the test. High antibody levels could only be maintained when Leishmania donovani was employed as the antigen, but considerable differences also occurred between the different strains of this species. The other antigens were weaker. No differences in antigenicity between amastigotes and promastigotes of the same strain were observed. It is important to select suitable antigens. Low titres may be of doubtful specificity and are a poor baseline for the fall in titre which is an essential index of effective treatment.Wir sammelten Parasiten und Seren von Reisenden, die aus verschiedenen endemischen Gebieten der Alten Welt mit einer Leishmaniasis nach Deutschland zurückkehrten. Die Antigenaktivitäten der isolierten und fortlaufend in Goldhamstern gehaltenenLeishmania-Stämme wurden im indirekten Immunofluoreszenztest (IFAT) verglichen. Die Antigenität wurde an Hand von Antikörpertitern in 18 Serumproben von 11 Patienten bewiesen. Neun Stämme desLeishmania donovani-Komplexes und vierLeishmania tropica-Isolate wurden in ihrem amastigoten Stadium miteinander verglichen. Hinzu kamen zwei Insekten-Flagellaten als Kulturformen:Strigomonas oncopelti undLeptomonas ctenocephali. 18 Serumproben von 11 Patienten standen für die Antikörperbestimmung mit diesen Antigenen zur Verfügung. Die maximalen Titerhöhen variierten in ein- und derselben antiserumprobe zum Teil erheblich, je nachdem, welches Antigen für den Test benutzt wurde. Hohe Antikörpertiter konnten nur erhalten werden, wennLeishmania donovani als Antigen vorlag, es ergaben sich aber auch zwischen den einzelnen Stämmen dieser Leishmaniaart erhebliche Unterschiede in der Antigenaktivität. Antigene anderer Art erwiesen sich als wenig wirksam. Zwischen amastigoten und promastigoten Entwicklungsformen einesLeishmania donovani-Stammes konnten keine Unterschiede in der Antigenaktivität erkannt werden. Für den Nachweis möglichst hoher Antikörpertiter im IFAT ist die Auswahl geeigneter Antigene von ausschlaggebender Bedeutung. Niedrige Titer erschweren deren Beurteilung als spezifisch und sind eine schlechte Ausgangsposition für die Beobachtung des obligatorischen Titerabfalles nach erfolgreicher Therapie