ALBERT

Description: Identification of retrotransposon insertions in nonmodel taxa can be technically challenging and costly. This has inhibited progress in understanding retrotransposon insertion dynamics outside of a few well-studied species. To address this problem, we have extended a retrotransposon-based capture and sequence method (ME-Scan [mobile element scanning]) to identify insertions belonging to the Ves family of short interspersed elements (SINEs) across seven species of the bat genus Myotis. We identified between 120,000 and 143,000 SINE insertions in six taxa lacking a draft genome by comparing to the M. lucifugus reference genome. On average, each Ves insertion was sequenced to 129.6 x coverage. When mapped back to the M. lucifugus reference genome, all insertions were confidently assigned within a 10-bp window. Polymorphic Ves insertions were identified in each taxon based on their mapped locations. Using cross-species comparisons and the identified insertion positions, a presence–absence matrix was created for approximately 796,000 insertions. Dollo parsimony analysis of more than 85,000 phylogenetically informative insertions recovered strongly supported, monophyletic clades that correspond with the biogeography of each taxa. This phylogeny is similar to previously published mitochondrial phylogenies, with the exception of the placement of M. vivesi. These results support the utility of our variation on ME-Scan to identify polymorphic retrotransposon insertions in taxa without a reference genome and for large-scale retrotransposon-based phylogenetics.

Description: Recent studies have found evidence of introgression from Neanderthals into modern humans outside of sub-Saharan Africa. Given the geographic range of Neanderthals, the findings have been interpreted as evidence of gene exchange between Neanderthals and modern humans descended from the Out-of-Africa (OOA) migration. Here, we examine an alternative interpretation in which the introgression occurred earlier within Africa, between ancestors or relatives of Neanderthals and a subset of African modern humans who were the ancestors of those involved in the OOA migration. Under the alternative model, if the population structure among present-day Africans predates the OOA migration, we might find some African populations show a signal of Neanderthal introgression whereas others do not. To test this alternative model, we compiled a whole-genome data set including 38 sub-Saharan Africans from eight populations and 25 non-African individuals from five populations. We assessed differences in the amount of Neanderthal-like single-nucleotide polymorphism alleles among these populations and observed up to 1.5% difference in the number of Neanderthal-like alleles among African populations. Further analyses suggest that these differences are likely due to recent non-African admixture in these populations. After accounting for recent non-African admixture, our results do not support the alternative model of older (e.g., 〉100 kya) admixture between modern humans and Neanderthal-like hominids within Africa.

Description: Motivation: Discovering the relevant therapeutic targets for drug-like molecules, or their unintended ‘off-targets’ that predict adverse drug reactions, is a daunting task by experimental approaches alone. There is thus a high demand to develop computational methods capable of detecting these potential interacting targets efficiently. Results: As biologically annotated chemical data are becoming increasingly available, it becomes feasible to explore such existing knowledge to identify potential ligand–target interactions. Here, we introduce an online implementation of a recently published computational model for target prediction, TarPred, based on a reference library containing 533 individual targets with 179 807 active ligands. TarPred accepts interactive graphical input or input in the chemical file format of SMILES. Given a query compound structure, it provides the top ranked 30 interacting targets. For each of them, TarPred not only shows the structures of three most similar ligands that are known to interact with the target but also highlights the disease indications associated with the target. This information is useful for understanding the mechanisms of action and toxicities of active compounds and can provide drug repositioning opportunities. Availability and implementation : TarPred is available at: http:// www.dddc.ac.cn/tarpred. Contact: hljiang@simm.ac.cn or myzheng@simm.ac.cn

Description: Transposable elements (TEs) are one of the most important features of genome architecture, so their evolution and relationship with host defense mechanisms have been topics of intense study, especially in model systems such as Drosophila melanogaster . Recently, a novel small RNA-based defense mechanism in animals called the Piwi-interacting RNA (piRNA) pathway was discovered to form an adaptive defense mechanism against TEs. To investigate the relationship between piRNA and TE content between strains of a species, we sequenced piRNAs from 16 inbred lines of D. melanogaster from the Drosophila Genetic Reference Panel. Instead of a global correlation of piRNA expression and TE content, we found evidence for a host response through de novo piRNA production from novel TE insertions. Although approximately 20% of novel TE insertions induced de novo piRNA production, the abundance of de novo piRNAs was low and did not markedly affect the global pool of ovarian piRNAs. Our results provide new insights into the evolution of TEs and the piRNA system in an important model organism.

Description: Macaques are the most widely distributed nonhuman primates and used as animal models in biomedical research. The availability of full-genome sequences from them would be essential to both biomedical and primate evolutionary studies. Previous studies have reported whole-genome sequences from rhesus macaque ( Macaca mulatta ) and cynomolgus macaque ( M. fascicularis , CE), both of which belong to the fascicularis group. Here, we present a 37-fold coverage genome sequence of the Tibetan macaque ( M. thibetana ; TM). TM is an endemic species to China belonging to the sinica group . On the basis of mapping to the rhesus macaque genome, we identified approximately 11.9 million single-nucleotide variants), of which 3.9 million were TM specific, as assessed by comparison two Chinese rhesus macaques (CR) and two CE genomes. Some genes carried TM-specific homozygous nonsynonymous variants (TSHNVs), which were scored as deleterious in human by both PolyPhen-2 and SIFT (Sorting Tolerant From Intolerant) and were enriched in the eye disease genes. In total, 273 immune response and disease-related genes carried at least one TSHNV. The heterozygosity rates of two CRs (0.002617 and 0.002612) and two CEs (0.003004 and 0.003179) were approximately three times higher than that of TM (0.000898). Polymerase chain reaction resequencing of 18 TM individuals showed that 29 TSHNVs exhibited high allele frequencies, thus confirming their low heterozygosity. Genome-wide genetic divergence analysis demonstrated that TM was more closely related to CR than to CE. We further detected unusual low divergence regions between TM and CR. In addition, after applying statistical criteria to detect putative introgression regions (PIRs) in the TM genome, up to 239,620 kb PIRs (8.84% of the genome) were identified. Given that TM and CR have overlapping geographical distributions, had the same refuge during the Middle Pleistocene, and show similar mating behaviors, it is highly likely that there was an ancient introgression event between them. Moreover, demographic inferences revealed that TM exhibited a similar demographic history as other macaques until 0.5 Ma, but then it maintained a lower effective population size until present time. Our study has provided new insight into the macaque evolutionary history, confirming hybridization events between macaque species groups based on genome-wide data.

Description: The chorioallantoic placenta connects mother and fetus in eutherian pregnancies. In order to understand the evolution of the placenta and provide further understanding of placenta biology, we sequenced the transcriptome of a term placenta of an African elephant ( Loxodonta africana ) and compared these data with RNA sequence and microarray data from other eutherian placentas including human, mouse, and cow. We characterized the composition of 55,910 expressed sequence tag (i.e., cDNA) contigs using our custom annotation pipeline. A Markov algorithm was used to cluster orthologs of human, mouse, cow, and elephant placenta transcripts. We found 2,963 genes are commonly expressed in the placentas of these eutherian mammals. Gene ontology categories previously suggested to be important for placenta function (e.g., estrogen receptor signaling pathway, cell motion and migration, and adherens junctions) were significantly enriched in these eutherian placenta–expressed genes. Genes duplicated in different lineages and also specifically expressed in the placenta contribute to the great diversity observed in mammalian placenta anatomy. We identified 1,365 human lineage–specific, 1,235 mouse lineage–specific, 436 cow lineage–specific, and 904 elephant-specific placenta-expressed (PE) genes. The most enriched clusters of human-specific PE genes are signal/glycoprotein and immunoglobulin, and humans possess a deeply invasive human hemochorial placenta that comes into direct contact with maternal immune cells. Inference of phylogenetically conserved and derived transcripts demonstrates the power of comparative transcriptomics to trace placenta evolution and variation across mammals and identified candidate genes that may be important in the normal function of the human placenta, and their dysfunction may be related to human pregnancy complications.