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Adaptive archaic hominin genes As they migrated out of Africa and into Europe and Asia, anatomically modern humans interbred with archaic hominins, such as Neanderthals and Denisovans. The result of this genetic introgression on the recipient populations has been of considerable interest, especially in cases of selection for specific archaic genetic variants. Hsieh et al. characterized adaptive structural variants and copy number variants that are likely targets of positive selection in Melanesians. Focusing on population-specific regions of the genome that carry duplicated genes and show an excess of amino acid replacements provides evidence for one of the mechanisms by which genetic novelty can arise and result in differentiation between human genomes. Science , this issue p. eaax2083

Dicentric chromosomes are products of genomic rearrangements that place two centromeres on the same chromosome. Due to the presence of two primary constrictions, they are inherently unstable and overcome their instability by epigenetically inactivating and/or deleting one of the two centromeres, thus resulting in functionally monocentric chromosomes that segregate normally during cell division. Our understanding to date of dicentric chromosome formation, behavior and fate has been largely inferred from observational studies in plants and humans as well as artificially produced de novo dicentrics in yeast and in human cells. We investigate the most recent product of a chromosome fusion event fixed in the human lineage, human chromosome 2, whose stability was acquired by the suppression of one centromere, resulting in a unique difference in chromosome number between humans (46 chromosomes) and our most closely related ape relatives (48 chromosomes). Using molecular cytogenetics, sequencing, and comparative sequence data, we deeply characterize the relicts of the chromosome 2q ancestral centromere and its flanking regions, gaining insight into the ancestral organization that can be easily broadened to all acrocentric chromosome centromeres. Moreover, our analyses offered the opportunity to trace the evolutionary history of rDNA and satellite III sequences among great apes, thus suggesting a new hypothesis for the preferential inactivation of some human centromeres, including IIq. Our results suggest two possible centromere inactivation models to explain the evolutionarily stabilization of human chromosome 2 over the last 5-6 million years. Our results strongly favor centromere excision through a one-step process.

Cytogenetics has historically played a key role in research on squirrel monkey (genus Saimiri) evolutionary biology. Squirrel monkeys have a diploid number of 2n = 44, but vary in fundamental number (FN). Apparently, differences in FN have phylogenetic implications and are correlated with geographic regions. A number of hypothetical mechanisms were proposed to explain difference in FN: translocations, heterochromatin, or, most commonly, pericentric inversions. Recently, an additional mechanism, centromere repositioning, was discovered, which can alter chromosome morphology and FN. Here, we used chromosome banding, chromosome painting, and BAC-FISH to test these hypotheses. We demonstrate that centromere repositioning on chromosomes 5 and 15 is the mechanism that accounts for differences in FN. Current phylogenomic trees of platyrrhines provide a temporal framework for evolutionary new centromeres (ENC) in Saimiri. The X-chromosome ENC could be up to 15 million years (my) old that on chromosome 5 as recent as 0.3 my. The chromosome 15 ENC is intermediate, as young as 2.24 my. All ENC have abundant satellite DNAs indicating that the maturation process was fairly rapid. Callithrix jacchus was used as an outgroup for the BAC-FISH data analysis. Comparison with scaffolds from the S. boliviensis genome revealed an error in the last marmoset genome release. Future research including at the sequence level will provide better understanding of chromosome evolution in Saimiri and other platyrrhines. Probably other cases of differences in chromosome morphology and FN, both within and between taxa, will be shown to be due to centromere repositioning and not pericentric inversions.

Grapevine (Vitis vinifera L.) is one of the world's most important crop plants, which is of large economic value for fruit and wine production. There is much interest in identifying genomic variations and their functional effects on inter-varietal, phenotypic differences. Using an approach developed for the analysis of human and mammalian genomes, which combines high-throughput sequencing, array comparative genomic hybridization, fluorescent in�situ hybridization and quantitative PCR, we created an inter-varietal atlas of structural variations and single nucleotide variants (SNVs) for the grapevine genome analyzing four economically and genetically relevant table grapevine varieties. We found 4.8 million SNVs and detected 8% of the grapevine genome to be affected by genomic variations. We identified more than 700 copy number variation (CNV) regions and more than 2000 genes subjected to CNV as potential candidates for phenotypic differences between varieties

Genetic differences that specify unique aspects of human evolution have typically been identified by comparative analyses between the genomes of humans and closely related primates, including more recently the genomes of archaic hominins. Not all regions of the genome, however, are equally amenable to such study. Recurrent copy number variation (CNV) at chromosome 16p11.2 accounts for approximately 1% of cases of autism and is mediated by a complex set of segmental duplications, many of which arose recently during human evolution. Here we reconstruct the evolutionary history of the locus and identify bolA family member 2 (BOLA2) as a gene duplicated exclusively in Homo sapiens. We estimate that a 95-kilobase-pair segment containing BOLA2 duplicated across the critical region approximately 282 thousand years ago (ka), one of the latest among a series of genomic changes that dramatically restructured the locus during hominid evolution. All humans examined carried one or more copies of the duplication, which nearly fixed early in the human lineage—a pattern unlikely to have arisen so rapidly in the absence of selection (P, Paul G. Allen Family Foundation (11631), Simons Foundation Autism Research Initiative (303241), Simons Foundation Autism Research Initiative (274424), United States. National Institutes of Health (2R01HG002385), United States. National Institutes of Health (TR01 MH095741), G. Harold and Leila Y. Mathers Foundation, JPB Foundation, Leona M. and Harry B. Helmsley Charitable Trust, National Science Foundation (U.S.) (DGE-1256082), National Institute of Mental Health (U.S.) (1F30MH105055-01)

Background Although many algorithms are now available that aim to characterize different classes of structural variation, discovery of balanced rearrangements such as inversions remains an open problem. This is mainly due to the fact that breakpoints of such events typically lie within segmental duplications or common repeats, which reduces the mappability of short reads. The algorithms developed within the 1000 Genomes Project to identify inversions are limited to relatively short inversions, and there are currently no available algorithms to discover large inversions using high throughput sequencing technologies. Results Here we propose a novel algorithm, Valor, to discover large inversions using new sequencing methods that provide long range information such as 10X Genomics linked-read sequencing, pooled clone sequencing, or other similar technologies that we commonly refer to as long range sequencing. We demonstrate the utility of Valor using both pooled clone sequencing and 10X Genomics linked-read sequencing generated from the genome of an individual from the HapMap project (NA12878). We also provide a comprehensive comparison of Valor against several state-of-the-art structural variation discovery algorithms that use whole genome shotgun sequencing data. Conclusions In this paper, we show that Valor is able to accurately discover all previously identified and experimentally validated large inversions in the same genome with a low false discovery rate. Using Valor, we also predicted a novel inversion, which we validated using fluorescent in situ hybridization. Valor is available at https://github.com/BilkentCompGen/Valor Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-3444-1) contains supplementary material, which is available to authorized users.

The centromere/kinetochore interaction is responsible for the pairing and segregation of replicated chromosomes in eukaryotes. Centromere DNA is portrayed as scarcely conserved, repetitive in nature, quickly evolving and protein-binding competent. Among primates, the major class of centromeric DNA is the pancentromeric α-satellite, made of arrays of 171 bp monomers, repeated in a head-to-tail pattern. α-satellite sequences can either form tandem heterogeneous monomeric arrays or assemble in higher-order repeats (HORs). Gorilla centromere DNA has barely been characterized and data are mainly based on hybridizations of human alphoid sequences. We isolated and finely characterized gorilla α-satellite sequences and revealed relevant structure and chromosomal distribution similarities with other great apes as well as gorilla-specific features, such as the uniquely octameric structure of the suprachromosomal family-2 (SF2). We demonstrated for the first time the orthologous localization of alphoid suprachromosomal families-1 and −2 (SF1 and SF2) between human and gorilla in contrast to chimpanzee centromeres. Finally, the discovery of a new 189 bp monomer type in gorilla centromeres unravels clues to the role of the centromere protein B, paving the way to solve the significance of the centromere DNA’s essential repetitive nature in association with its function and the peculiar evolution of the α-satellite sequence.

There are many different forms of genomic structural variation that can be broadly classified as copy number variation (CNV) and balanced rearrangements. Although many algorithms are now available in the literature that aim to characterize CNVs, discovery of balanced rearrangements (inversions and translocations) remains an open problem. This is mainly because the breakpoints of such events typically lie within segmental duplications and common repeats, which reduce the mappability of short reads. The 1000 Genomes Project spearheaded the development of several methods to identify inversions, however, they are limited to relatively short inversions, and there are currently no available algorithms to discover large inversions using high throughput sequencing technologies (HTS). Here we propose to use a sequencing method (Kitzman et al., 2011) originally developed to improve haplotype resolution to characterize large genomic inversions. This method, called pooled clone sequencing, merges the advantages of clone based sequencing approach with the speed and cost efficiency of HTS technologies. Using data generated with pooled clone sequencing method, we developed a novel algorithm, dipSeq, to discover large inversions (>500 Kbp). We show the power of dipSeq first on simulated data, and then apply it to the genome of a HapMap individual (NA12878). We were able to accurately discover all previously known and experimentally validated large inversions in the same genome. We also identified a novel inversion, and confirmed using fluorescent in situ hybridization. Availability: Implementation of the dipSeq algorithm is available at https://github.com/BilkentCompGen/dipseq

Genome mutations represent a source of variability on which selective pressure acts: negative changes are purged from the populations, whereas positive and neutral changes may be fixed. Segmental duplications (SDs) in the human genome trigger mutations such as structural rearrangements (duplications, deletions, inversions and translocations), thus playing a crucial role in human disease and genome evolution. Several human diseases (genomic disorders) are caused by non-allelic homologous recombination (NAHR) between highly similar SDs, as well as gene-containing SDs were crucial to survival and adaptation of human species during evolution. Moreover, both from a pathological and an evolutionary point of view, SDs represent critically important regions for acentric fragment rescue during neocentromerization process. In this light, disease and evolution can be considered as ‘two sides of the same coin’, where the coin represents the SD-mediated chromosomal rearrangements. Key Concepts Segmental duplications (SDs) create variability in human genome. Mediating non-allelic homologous recombination (NAHR) segmental duplications mediate chromosomal unbalance. Duplicated genes may show pattern of expression different from ancestral gene. Segmental duplications are the remains of ancestral pericentromeric regions. Neocentromere can generate at loci where ancestral centromere were located. Keywords: genomic disorders; mammals; variability; polymorphisms; primates; neocentromere

Hormozdiari, Fereydoun et al.-- Great Ape Genome Project, We analyzed 83 fully sequenced great ape genomes for mobile element insertions, predicting a total of 49,452 fixed and polymorphic Alu and long interspersed element 1 (L1) insertions not present in the human reference assembly and assigning each retrotransposition event to a different time point during great ape evolution. We used these homoplasy-free markers to construct a mobile element insertions-based phylogeny of humans and great apes and demonstrate their differential power to discern ape subspecies and populations. Within this context, we find a good correlation between L1 diversity and single-nucleotide polymorphism heterozygosity (r2 =0.65) in contrast to Alu repeats, which show little correlation (r2 =0.07). We estimate that the rate of Alu retrotransposition has differed by a factor of 15-fold in these lineages. Humans, chimpanzees, and bonobos show the highest rates of Alu accumulation-the latter two since divergence 1.5 Mya. The L1 insertion rate, in contrast, has remained relatively constant, with rates differing by less than a factor of three. We conclude that Alu retrotransposition has been the most variable form of genetic variation during recent human-great ape evolution, with increases and decreases occurring over very short periods of evolutionary time., This work was supported by National Institutes of Health (NIH) Grant HG002385 (to E.E.E.), NIH R01 Grant GM59290 (to M.A.B.), an European Research Council Starting Grant (260372) (to T.M.-B.), and Ministerio de Ciencia e Innovacion (MICINN - Spain) BFU2011-28549 (to T.M.-B.). P.H.S. is supported by a Howard Hughes International Student Fellowship; E.E.E. is an Investigator of the Howard Hughes Medical Institute; and T.M.-B. is a Research Investigator (Institut Catala d’Estudis i Recerca Avancats de la Generalitat de Catalunya).