Neandertals, the closest evolutionary relatives of present-day humans, lived in large parts of Europe and western Asia before disappearing 30,000 years ago. We present a draft sequence of the Neandertal genome composed of more than 4 billion nucleotides from three individuals. Comparisons of the Neandertal genome to the genomes of five present-day humans from different parts of the world identify a number of genomic regions that may have been affected by positive selection in ancestral modern humans, including genes involved in metabolism and in cognitive and skeletal development. We show that Neandertals shared more genetic variants with present-day humans in Eurasia than with present-day humans in sub-Saharan Africa, suggesting that gene flow from Neandertals into the ancestors of non-Africans occurred before the divergence of Eurasian groups from each other.

We present a baculovirus-based protein engineering method that enables site-specific introduction of unique functionalities in a eukaryotic protein complex recombinantly produced in insect cells. We demonstrate the versatility of this efficient and robust protein production platform, 'MultiBacTAG', (i) for the fluorescent labeling of target proteins and biologics using click chemistries, (ii) for glycoengineering of antibodies, and (iii) for structure-function studies of novel eukaryotic complexes using single-molecule Förster resonance energy transfer as well as site-specific crosslinking strategies.

Although nucleotide resolution maps of genomic structural variants (SVs) have provided insights into the origin and impact of phenotypic diversity in humans, comparable maps in nonhuman primates have thus far been lacking. Using massively parallel DNA sequencing, we constructed fine-resolution genomic structural variation maps in five chimpanzees, five orang-utans, and five rhesus macaques. The SV maps, which are comprised of thousands of deletions, duplications, and mobile element insertions, revealed a high activity of retrotransposition in macaques compared with great apes. By comparison, nonallelic homologous recombination is specifically active in the great apes, which is correlated with architectural differences between the genomes of great apes and macaque. Transcriptome analyses across nonhuman primates and humans revealed effects of species-specific whole-gene duplication on gene expression. We identified 13 gene duplications coinciding with the species-specific gain of tissue-specific gene expression in keeping with a role of gene duplication in the promotion of diversification and the acquisition of unique functions. Differences in the present day activity of SV formation mechanisms that our study revealed may contribute to ongoing diversification and adaptation of great ape and Old World monkey lineages. genome evolution | retrotransposons | neofunctionalization | copy-number variation G enomic structural variants (SVs), including copy number variants and balanced SV forms (such as inversions), are a major source of human genetic variation (1, 2). The development of massively parallel sequencing (MPS) to characterize SVs (3-5) has enabled comprehensive analyses of origin and functional impact of SVs in humans (3, 6). Although SVs are presumed to play a major role in primate evolution and phenotypic variation (7) as well, empirical evidence showing such a role remains scarce (8). Comparative analyses of reference genome assemblies of the chimpanzee (9), orang-utan (10), and rhesus macaque (11) have provided some initial insights into large-scale structural changes in primate genome evolution (12). Microarray technology-based surveys have provided additional glimpses of the abundance of polymorphic unbalanced SVs (i.e., copy number variants) in different primate species, enabling the construction of SV maps at a resolution of tens to hundreds of kilobases (13-16).Thus far, despite ongoing progress in assessing SNP variation in primates (10,(17)(18)(19), no study has leveraged MPS technology for ascertaining inter-and intraspecies SVs in different primates. We, therefore, performed MPS-based genome analyses in five individuals from each of these primate species, Pan troglodytes (chimpanzee), Pongo abelii (orang-utan), and Macaca mulatta (rhesus macaque), to construct comprehensive SV maps in these species. Our analyses have revealed marked differences in SV formation mechanism activities and further yielded a complex relationship between genomic copy number and gene expression patterns, with several gen...

BackgroundCGGBP1 is a repetitive DNA-binding transcription regulator with target sites at CpG-rich sequences such as CGG repeats and Alu-SINEs and L1-LINEs. The role of CGGBP1 as a possible mediator of CpG methylation however remains unknown. At CpG-rich sequences cytosine methylation is a major mechanism of transcriptional repression. Concordantly, gene-rich regions typically carry lower levels of CpG methylation than the repetitive elements. It is well known that at interspersed repeats Alu-SINEs and L1-LINEs high levels of CpG methylation constitute a transcriptional silencing and retrotransposon inactivating mechanism.ResultsHere, we have studied genome-wide CpG methylation with or without CGGBP1-depletion. By high throughput sequencing of bisulfite-treated genomic DNA we have identified CGGBP1 to be a negative regulator of CpG methylation at repetitive DNA sequences. In addition, we have studied CpG methylation alterations on Alu and L1 retrotransposons in CGGBP1-depleted cells using a novel bisulfite-treatment and high throughput sequencing approach.ConclusionsThe results clearly show that CGGBP1 is a possible bidirectional regulator of CpG methylation at Alus, and acts as a repressor of methylation at L1 retrotransposons.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1593-2) contains supplementary material, which is available to authorized users.