ALBERT

Description: Horizontal gene transfer (HGT) has been recognized to be an important mechanism that shaped the evolution and genomes of prokaryotes and unicellular eukaryotes. However, HGT is regarded to be exceedingly rare among eukaryotes. We discovered massive transfers of a DNA transposon, a Tc1 element encoding a transposase, between multiple teleost fishes and lampreys that last shared a common ancestor over 500 Ma. Members of this group of Tc1 elements were found to exhibit a mosaic phylogenetic distribution, yet their sequences were highly similar even between distantly related lineages (95%–99% identity). Our molecular phylogenetic analyses suggested that horizontal transfers of this element happened repeatedly, involving multiple teleost fishes that are phylogenetically only distantly related. Interestingly, almost all the affected teleost lineages are also known to be subject to lamprey parasitism, suggesting that the horizontal transfers between vertebrates might have occurred through parasite–host interaction. The genomes of several northern hemisphere lamprey species, including that of the sea lamprey ( Petromyzon marinus ), were found to contain thousands of copies of the foreign elements. Impact of this event is discussed in relation to other peculiar genomic features of lampreys.

Description: The impact of cigarette smoking can persist for extended periods following smoking cessation and may involve epigenetic reprogramming. Changes in DNA methylation associated with smoking may help to identify molecular pathways that contribute to the latency between exposure and disease onset. Cross-sectional cohort data from subjects in the International COPD Genetics Network ( n = 1085) and the Boston Early-Onset COPD study ( n = 369) were analyzed as the discovery and replication cohorts, respectively. Genome-wide methylation data on 27 578 CpG sites in 14 475 genes were obtained on DNA from peripheral blood leukocytes using the Illumina HumanMethylation27K Beadchip in both cohorts. We identified 15 sites significantly associated with current smoking, 2 sites associated with cumulative smoke exposure, and, within the subset of former smokers, 3 sites associated with time since quitting cigarettes. Two loci, factor II receptor-like 3 ( F2RL3 ) and G-protein-coupled receptor 15 ( GPR15 ), were significantly associated in all three analyses and were validated by pyrosequencing. These findings (i) identify a novel locus ( GPR15 ) associated with cigarette smoking and (ii) suggest the existence of dynamic, site-specific methylation changes in response to smoking which may contribute to the extended risks associated with cigarette smoking that persist after cessation.

Description: Initial subduction-related boninitic magmatism occurred between 48 and 44 Ma in the Izu–Bonin–Mariana (IBM) arc. High-Mg adakites and low-Ca boninites have been dredged from the Bonin Ridge fore-arc seamount. Whole-rock 40 Ar/ 39 Ar ages suggest that the boninite (44·0 ± 1·4 Ma) and adakite (43·1 ± 1·0 and 40·8 ± 0·8 Ma) magmatism overlapped, or that the adakite magmatism occurred slightly later than the boninite magmatism. The low-Ca boninites are high-Mg andesites and exhibit U-shaped rare earth element (REE) patterns with an elevated average Mg# of 0·78 [Mg# = Mg/(Mg + Fe) molar ratio] and Ni content of 667 ppm. The high-Mg adakites are andesitic to dacitic in composition; they exhibit markedly high Sr contents and low Y contents and are highly enriched in light REE but depleted in heavy REE, with an average Mg# of 0·79 and Ni content of 433 ppm. A geochemical mass-balance model (Arc Basalt Simulator Version 3) indicates that both magma types could be generated by partial melting of a depleted mantle source fluxed by water-rich slab-derived melts in a hot subduction environment, comparable with the present-day South Chile (ridge subduction) or Southwest Japan (young slab subduction) arcs. An extremely high slab melt flux of 22% is required for the formation of the high-Mg adakite, whereas a low flux of 3% is sufficient for the low-Ca boninite. The low-Ca boninite requires a high-temperature shallow slab (854°C, 2·7 GPa on average), consisting of altered oceanic crust of the Pacific plate and volcaniclastic sediments from HIMU seamounts, and high-temperature shallow mantle melting (1216°C, 0·8 GPa) of depleted Indian mid-ocean ridge basalt (MORB)-type mantle. These modelled conditions are consistent with the occurrence of hot shallow mantle wedge melting in the initial subduction zone at the boundary between Pacific- and Indian-type mantle domains, as suggested by previous studies. In contrast, high-Mg adakite requires a higher temperature and deeper slab (929°C, 4·1 GPa), with the same slab components and slightly deeper but less hot melting (1130°C, 1·1 GPa) of HIMU-type depleted mantle, to satisfy the low Hf isotope ratios. This may occur because of the subsequent cooling of the mantle wedge by the establishment of the subduction system after the boninite magmatism and involvement of a small volume of an isotopically enriched mantle source embedded in the Indian-type mantle. The petrogenetic conditions provide constraints for reconstructing the tectonic settings of the early IBM arc. The hot subduction model would be consistent with the tectonic models with regard to the initiation of subduction associated with fore-arc spreading; this allowed the upwelling of the asthenospheric mantle to generate slab melts from the old Pacific plate slab and hot shallow mantle melting by slab melt fluxing for both boninite and adakite activities.

Description: A novel computational method for detecting identical-by-descent (IBD) chromosomal segments between sequenced genomes is presented. It utilizes the distribution patterns of v ery r are g enetic v ariants (vrGVs), which have minor allele frequencies 〈0.2%. Contrary to the existing probabilistic approaches our method is rather deterministic, because it considers a group of very rare events which cannot happen together only by chance. This method has been applied for exhaustive computational search of shared IBD segments among 1,092 sequenced individuals from 14 populations. It demonstrated that clusters of vrGVs are unique and powerful markers of genetic relatedness, that uncover IBD chromosomal segments between and within populations, irrespective of whether divergence was recent or occurred hundreds-to-thousands of years ago. We found that several IBD segments are shared by practically any possible pair of individuals belonging to the same population. Moreover, shared short IBD segments (median size 183 kb) were found in 10% of inter-continental human pairs, each comprising of a person from sub-Saharan Africa and a person from Southern Europe. The shortest shared IBD segments (median size 54 kb) were found in 0.42% of inter-continental pairs composed of individuals from Chinese/Japanese populations and Africans from Kenya and Nigeria. Knowledge of inheritance of IBD segments is important in clinical case–control and cohort studies, since unknown distant familial relationships could compromise interpretation of collected data. Clusters of vrGVs should be useful markers for familial relationship and common multifactorial disorders.

Description: Although the Matuyama–Brunhes boundary (MBB) in the Chinese Loess Plateau (CLP) is very important in reliably correlating Quaternary loess with other sediments in the world, particularly with marine and polar ice cores, its exact stratigraphic position remains controversial. Previous investigations usually placed the MBB between paleosol unit S8 and loess unit L8 in various locations. To better understand the spatial differences in the MBB position, a high-resolution paleomagnetic study was conducted in a loess section of the Lantian Basin at the southern margin of the CLP. The results show that the MBB is situated in the middle of the relatively weak paleosol unit S7, consistent with a recent report on the MBB based on a 10 Be study from the Xifeng and Luochuan loess sections of the central CLP. However, the regional anomalously low magnetic susceptibility in paleosols S7 and S8 indicates that it is more reliable to determine the paleoclimate boundaries between loess and paleosol horizons of this segment with median grain size. Then, the MBB in the Yushan section can be correlated with the bottom of paleosol S7, corresponding to the older part of interglacial marine isotope stage 19. This result temporally reconciles the striking discrepancy of the position of the MBB recorded in between loess and other typical sedimentary sequences, and further confirms that the stratigraphic position of the MBB could spatially vary to a certain extent due to regional sedimentary or paleoclimatic conditions in the marginal areas of the CLP. In the Yushan section, the high-frequency variations of paleomagnetic directions during a long period of ~31 ka before the MBB, however, could not be attributed to a genuine response to the true geomagnetic behaviour. Moreover, the climate offset defined by the magnetic susceptibility and median grain size of the section can be preliminarily attributed to the regional geology and paleoenvironment background. A multiproxy-based stratigraphic division is considered very necessary when paleomagnetic and climatic boundaries are defined exactly in a specific area of the southern CLP.

Description: Nucleotide sequence differences on the whole-genome scale have been computed for 1,092 people from 14 populations publicly available by the 1000 Genomes Project. Total number of differences in genetic variants between 96,464 human pairs has been calculated. The distributions of these differences for individuals within European, Asian, or African origin were characterized by narrow unimodal peaks with mean values of 3.8, 3.5, and 5.1 million, respectively, and standard deviations of 0.1–0.03 million. The total numbers of genomic differences between pairs of all known relatives were found to be significantly lower than their respective population means and in reverse proportion to the distance of their consanguinity. By counting the total number of genomic differences it is possible to infer familial relations for people that share down to 6% of common loci identical-by-descent. Detection of familial relations can be radically improved when only very rare genetic variants are taken into account. Counting of total number of shared very rare single nucleotide polymorphisms (SNPs) from whole-genome sequences allows establishing distant familial relations for persons with eighth and ninth degrees of relationship. Using this analysis we predicted 271 distant familial pairwise relations among 1,092 individuals that have not been declared by 1000 Genomes Project. Particularly, among 89 British and 97 Chinese individuals we found three British–Chinese pairs with distant genetic relationships. Individuals from these pairs share identical-by-descent DNA fragments that represent 0.001%, 0.004%, and 0.01% of their genomes. With affordable whole-genome sequencing techniques, very rare SNPs should become important genetic markers for familial relationships and population stratification.

Description: Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P -values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P 〈 5 x 10 –8 , and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19–1.40) and P = 7.63 x 10 –10 . An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8 / ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8 . Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.

Description: Altered miRNA expression is believed to play a crucial role in a variety of human cancers; however, the mechanisms leading to the dysregulation of miRNA expression remain elusive. In this study, we report that the human Y box-binding protein (YB-1), a major mRNA packaging protein, is a novel modulator of miRNA processing in glioblastoma multiforme (GBM). Using individual nucleotide-resolution crosslinking immunoprecipitation coupled to deep sequencing (iCLIP-seq), we performed the first genome-wide analysis of the in vivo YB-1-RNA interactions and found that YB-1 preferentially recognizes a UYAUC consensus motif and binds to the majority of coding gene transcripts including pre-mRNAs and mature mRNAs. Remarkably, our data show that YB-1 also binds extensively to the terminal loop region of pri-/pre-miR-29b-2 and regulates the biogenesis of miR-29b-2 by blocking the recruitment of microprocessor and Dicer to its precursors. Furthermore, we show that down-regulation of miR-29b by YB-1, which is up-regulated in GBM, is important for cell proliferation. Together, our findings reveal a novel function of YB-1 in regulating non-coding RNA expression, which has important implications in tumorigenesis.

Description: Mammalian genomes are replete with millions of polymorphic sites, among which those genetic variants that are colocated on the same chromosome and exist close to one another form blocks of closely linked mutations known as haplotypes. The linkage within haplotypes is constantly disrupted due to meiotic recombination events. Whole ensembles of such numerous haplotypes are subjected to evolutionary pressure, where mutations influence each other and should be considered as a whole entity—a gigantic matrix, unique for each individual genome. This idea was implemented into a computational approach, named Genome Evolution by Matrix Algorithms (GEMA) to model genomic changes taking into account all mutations in a population. GEMA has been tested for modeling of entire human chromosomes. The program can precisely mimic real biological processes that have influence on genome evolution such as: 1) Authentic arrangements of genes and functional genomic elements, 2) frequencies of various types of mutations in different nucleotide contexts, and 3) nonrandom distribution of meiotic recombination events along chromosomes. Computer modeling with GEMA has demonstrated that the number of meiotic recombination events per gamete is among the most crucial factors influencing population fitness. In humans, these recombinations create a gamete genome consisting on an average of 48 pieces of corresponding parental chromosomes. Such highly mosaic gamete structure allows preserving fitness of population under the intense influx of novel mutations (40 per individual) even when the number of mutations with deleterious effects is up to ten times more abundant than those with beneficial effects.

Description: This paper reports an approach for estimating thinning-induced changes in N and P budgets in jarrah ( Eucalyptus marginata ) forest in the Wungong catchment of Western Australia. Two thinning strategies, herbicide injection and selective removal, were tested and nutrient budgets were constructed for soil, litter and tree biomass. The effects of thinning were evaluated based on pre-thinning biomass allocation and on reductions in biomass after thinning. Tree above ground biomass was 399 ton ha -1 , from which the selective logging removed 18.7 ton ha -1 or 5 per cent of the N and 4 per cent of the P. Thinning residues from stem injection of herbicide contained fivefold more nutrients than the ground litter. Top soil was the primary nutrient store but only 1–2 per cent of total N and P were in available forms. In contrast, fine litter materials in thinned sites may release 4.8–5.7 kg P ha –1 via leaching over the rainy months. Cut branches and dead stems stored 176 kg N ha –1 and 7.0 kg P ha –1 but would decompose over many decades. Our results indicate that both thinning strategies would increase nutrient cycling in the forest, while the implications of thinning-induced nutrient supply for the growth of remaining vegetation, understorey competition and ecosystem health need further examination.