Detection and analysis of ancient segmental duplications in mammalian genomes.
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SUBMITTER: Pu L
PROVIDER: S-EPMC5991524 | biostudies-literature | 2018 Jun
REPOSITORIES: biostudies-literature
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Detection and analysis of ancient segmental duplications in mammalian genomes.
Pu Lianrong L Lin Yu Y Pevzner Pavel A PA
Genome research 20180507 6
Although segmental duplications (SDs) represent hotbeds for genomic rearrangements and emergence of new genes, there are still no easy-to-use tools for identifying SDs. Moreover, while most previous studies focused on recently emerged SDs, detection of ancient SDs remains an open problem. We developed an SDquest algorithm for SD finding and applied it to analyzing SDs in human, gorilla, and mouse genomes. Our results demonstrate that previous studies missed many SDs in these genomes and show tha ...[more]
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Project description:Structural variation among genomes is now viewed to be as important as single nucleoid polymorphisms in influencing the phenotype and evolution of a species. Segmental duplication (SD) is defined as segments of DNA with homologous sequence.Here, we performed a systematic analysis of segmental duplications (SDs) among five lepidopteran reference genomes (Plutella xylostella, Danaus plexippus, Bombyx mori, Manduca sexta and Heliconius melpomene) to understand their potential impact on the evolution of these species. We find that the SDs content differed substantially among species, ranging from 1.2% of the genome in B. mori to 15.2% in H. melpomene. Most SDs formed very high identity (similarity higher than 90%) blocks but had very few large blocks. Comparative analysis showed that most of the SDs arose after the divergence of each linage and we found that P. xylostella and H. melpomene showed more duplications than other species, suggesting they might be able to tolerate extensive levels of variation in their genomes. Conserved ancestral and species specific SD events were assessed, revealing multiple examples of the gain, loss or maintenance of SDs over time. SDs content analysis showed that most of the genes embedded in SDs regions belonged to species-specific SDs ("Unique" SDs). Functional analysis of these genes suggested their potential roles in the lineage-specific evolution. SDs and flanking regions often contained transposable elements (TEs) and this association suggested some involvement in SDs formation. Further studies on comparison of gene expression level between SDs and non-SDs showed that the expression level of genes embedded in SDs was significantly lower, suggesting that structure changes in the genomes are involved in gene expression differences in species.The results showed that most of the SDs were "unique SDs", which originated after species formation. Functional analysis suggested that SDs might play different roles in different species. Our results provide a valuable resource beyond the genetic mutation to explore the genome structure for future Lepidoptera research.
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Project description:BackgroundSegmental duplications (SDs), also known as low-copy repeats, are DNA sequences of length greater than 1 kb which are duplicated with a high degree of sequence identity (greater than 90%) causing instability in genomes. SDs are generally found in the genome as mosaic forms of duplicated sequences which are generated by a two-step process: first, multiple duplicated sequences are aggregated at specific genomic regions, and then, these primary duplications undergo multiple secondary duplications. However, the mechanism of how duplicated sequences are aggregated in the first place is not well understood.ResultsBy analyzing the distribution of microsatellite sequences among twenty insect species in a genome-wide manner it was found that pairs of microsatellites along with the intervening sequences were duplicated multiple times in each genome. They were found as low copy repeats or segmental duplications when the duplicated loci were greater than 1 kb in length and had greater than 90% sequence similarity. By performing a sliding-window genomic analysis for number of paired microsatellites and number of segmental duplications, it was observed that regions rich in repetitive paired microsatellites tend to get richer in segmental duplication suggesting a "rich-gets-richer" mode of aggregation of the duplicated loci in specific regions of the genome. Results further show that the relationship between number of paired microsatellites and segmental duplications among the species is independent of the known phylogeny suggesting that association of microsatellites with segmental duplications may be a species-specific evolutionary process. It was also observed that the repetitive microsatellite pairs are associated with gene duplications but those sequences are rarely retained in the orthologous genes between species. Although some of the duplicated sequences with microsatellites as termini were found within transposable elements (TEs) of Drosophila, most of the duplications are found in the TE-free and gene-free regions of the genome.ConclusionThe study clearly suggests that microsatellites are instrumental in extensive sequence duplications that may contribute to species-specific evolution of genome plasticity in insects.
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Project description:Mammalian genomes are densely populated with long duplicated sequences. In this paper, we demonstrate the existence of doublets, short duplications between 25 and 100 bp, distinct from previously described repeats. Each doublet is a pair of exact matches, separated by some distance. The distribution of these intermatch distances is strikingly nonrandom. An unexpectedly high number of doublets have matches either within 100 bp (adjacent) or at distances tightly concentrated approximately 1,000 bp apart (nearby). We focus our study on these proximate doublets. First, they tend to have both matches on the same strand. By comparing nearby doublets shared in human and chimpanzee, we can also see that these doublets seem to arise by an insertion event that produces a copy without markedly affecting the surrounding sequence. Most doublets in humans are shared with chimpanzee, but many new pairs arose after the divergence of the species. Doublets found in human but not chimpanzee are most often composed of almost tandem matches, whereas older doublets (found in both species) are more likely to have matches spaced by approximately 1 kb, indicating that the nearly tandem doublets may be more dynamic. The spacing of doublets is highly conserved. So far, we have found clearly recognizable doublets in the following genomes: Homo sapiens, Mus musculus, Arabidopsis thaliana, and Caenorhabditis elegans, indicating that the mechanism generating these doublets is widespread. A mechanism that generates short local duplications while conserving polarity could have a profound impact on the evolution of regulatory and protein-coding sequences.
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Project description:BackgroundHemorrhagic diseases from Ebolavirus and Marburgvirus (Filoviridae) infections can be dangerous to humans because of high fatality rates and a lack of effective treatments or vaccine. Although there is evidence that wild mammals are infected by filoviruses, the biology of host-filovirus systems is notoriously poorly understood. Specifically, identifying potential reservoir species with the expected long-term coevolutionary history of filovirus infections has been intractable. Integrated elements of filoviruses could indicate a coevolutionary history with a mammalian reservoir, but integration of nonretroviral RNA viruses is thought to be nonexistent or rare for mammalian viruses (such as filoviruses) that lack reverse transcriptase and replication inside the nucleus. Here, we provide direct evidence of integrated filovirus-like elements in mammalian genomes by sequencing across host-virus gene boundaries and carrying out phylogenetic analyses. Further we test for an association between candidate reservoir status and the integration of filoviral elements and assess the previous age estimate for filoviruses of less than 10,000 years.ResultsPhylogenetic and sequencing evidence from gene boundaries was consistent with integration of filoviruses in mammalian genomes. We detected integrated filovirus-like elements in the genomes of bats, rodents, shrews, tenrecs and marsupials. Moreover, some filovirus-like elements were transcribed and the detected mammalian elements were homologous to a fragment of the filovirus genome whose expression is known to interfere with the assembly of Ebolavirus. The phylogenetic evidence strongly indicated that the direction of transfer was from virus to mammal. Eutherians other than bats, rodents, and insectivores (i.e., the candidate reservoir taxa for filoviruses) were significantly underrepresented in the taxa with detected integrated filovirus-like elements. The existence of orthologous filovirus-like elements shared among mammalian genera whose divergence dates have been estimated suggests that filoviruses are at least tens of millions of years old.ConclusionsOur findings indicate that filovirus infections have been recorded as paleoviral elements in the genomes of small mammals despite extranuclear replication and a requirement for cooption of reverse transcriptase. Our results show that the mammal-filovirus association is ancient and has resulted in candidates for functional gene products (RNA or protein).
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Project description:BackgroundDuplicated sequences are an important source of gene innovation and structural variation within mammalian genomes. We performed the first systematic and genome-wide analysis of segmental duplications in the modern domesticated cattle (Bos taurus). Using two distinct computational analyses, we estimated that 3.1% (94.4 Mb) of the bovine genome consists of recently duplicated sequences (>or= 1 kb in length, >or= 90% sequence identity). Similar to other mammalian draft assemblies, almost half (47% of 94.4 Mb) of these sequences have not been assigned to cattle chromosomes.ResultsIn this study, we provide the first experimental validation large duplications and briefly compared their distribution on two independent bovine genome assemblies using fluorescent in situ hybridization (FISH). Our analyses suggest that the (75-90%) of segmental duplications are organized into local tandem duplication clusters. Along with rodents and carnivores, these results now confidently establish tandem duplications as the most likely mammalian archetypical organization, in contrast to humans and great ape species which show a preponderance of interspersed duplications. A cross-species survey of duplicated genes and gene families indicated that duplication, positive selection and gene conversion have shaped primates, rodents, carnivores and ruminants to different degrees for their speciation and adaptation. We identified that bovine segmental duplications corresponding to genes are significantly enriched for specific biological functions such as immunity, digestion, lactation and reproduction.ConclusionOur results suggest that in most mammalian lineages segmental duplications are organized in a tandem configuration. Segmental duplications remain problematic for genome and assembly and we highlight genic regions that require higher quality sequence characterization. This study provides insights into mammalian genome evolution and generates a valuable resource for cattle genomics research.
| S-EPMC2796684 | biostudies-literature
Project description:Diploid genomes with divergent chromosomes present special problems for assembly software as two copies of especially polymorphic regions may be mistakenly constructed, creating the appearance of a recent segmental duplication. We developed a method for identifying such false duplications and applied it to four vertebrate genomes. For each genome, we corrected mis-assemblies, improved estimates of the amount of duplicated sequence, and recovered polymorphisms between the sequenced chromosomes.
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Project description:BACKGROUND: Segmental duplications (SDs) are blocks of genomic sequence of 1-200 kb that map to different loci in a genome and share a sequence identity > 90%. SDs show at the sequence level the same characteristics as other regions of the human genome: they contain both high-copy repeats and gene sequences. SDs play an important role in genome plasticity by creating new genes and modeling genome structure. Although data is plentiful for mammals, not much was known about the representation of SDs in plant genomes. In this regard, we performed a genome-wide analysis of high-identity SDs on the sequenced grapevine (Vitis vinifera) genome (PN40024). RESULTS: We demonstrate that recent SDs (> 94% identity and >= 10 kb in size) are a relevant component of the grapevine genome (85 Mb, 17% of the genome sequence). We detected mitochondrial and plastid DNA and genes (10% of gene annotation) in segmentally duplicated regions of the nuclear genome. In particular, the nine highest copy number genes have a copy in either or both organelle genomes. Further we showed that several duplicated genes take part in the biosynthesis of compounds involved in plant response to environmental stress. CONCLUSIONS: These data show the great influence of SDs and organelle DNA transfers in modeling the Vitis vinifera nuclear DNA structure as well as the impact of SDs in contributing to the adaptive capacity of grapevine and the nutritional content of grape products through genome variation. This study represents a step forward in the full characterization of duplicated genes important for grapevine cultural needs and human health.
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Project description:Limited comparative studies suggest that the human genome is particularly enriched for recent segmental duplications. The extent of segmental duplications in other mammalian genomes is unknown and confounded by methodological differences in genome assembly. Here, we present a detailed analysis of recent duplication content within the mouse genome using a whole-genome assembly comparison method and a novel assembly independent method, designed to take advantage of the reduced allelic variation of the C57BL/6J strain. We conservatively estimate that approximately 57% of all highly identical segmental duplications (>or=90%) were misassembled or collapsed within the working draft WGS assembly. The WGS approach often leaves duplications fragmented and unassigned to a chromosome when compared with the clone-ordered-based approach. Our preliminary analysis suggests that 1.7%-2.0% of the mouse genome is part of recent large segmental duplications (about half of what is observed for the human genome). We have constructed a mouse segmental duplication database to aid in the characterization of these regions and their integration into the final mouse genome assembly. This work suggests significant biological differences in the architecture of recent segmental duplications between human and mouse. In addition, our unique method provides the means for improving whole-genome shotgun sequence assembly of mouse and future mammalian genomes.
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Project description:Ancient DNA is a valuable tool for investigating genetic and evolutionary history that can also provide detailed profiles of the lives of ancient individuals. In this study, we develop a generalised computational approach to detect aneuploidies (atypical autosomal and sex chromosome karyotypes) in the ancient genetic record and distinguish such karyotypes from contamination. We confirm that aneuploidies can be detected even in low-coverage genomes ( ~ 0.0001-fold), common in ancient DNA. We apply this method to ancient skeletal remains from Britain to document the first instance of mosaic Turner syndrome (45,X0/46,XX) in the ancient genetic record in an Iron Age individual sequenced to average 9-fold coverage, the earliest known incidence of an individual with a 47,XYY karyotype from the Early Medieval period, as well as individuals with Klinefelter (47,XXY) and Down syndrome (47,XY, + 21). Overall, our approach provides an accessible and automated framework allowing for the detection of individuals with aneuploidies, which extends previous binary approaches. This tool can facilitate the interpretation of burial context and living conditions, as well as elucidate past perceptions of biological sex and people with diverse biological traits.
| S-EPMC10784527 | biostudies-literature
Project description:BackgroundSegmental duplications (SDs) or low-copy repeats play important roles in both gene and genome evolution. SDs have been extensively investigated in many organisms, however, there is no information about SDs in the silkworm, Bombyx mori.ResultIn this study, we identified and annotated the SDs in the silkworm genome. Our results suggested that SDs constitute ~1.4% of the silkworm genome sequence (≥1 kb in length and ≥90% in the identity of sequence); the number is similar to that in Drosophila melanogaster but smaller than mammalian organisms. Almost half (42%) of the SD sequences are not assigned to chromosomes, indicating that the SDs are challenges for the assembling of genome sequences. We also provided experimental validation of large duplications using qPCR. The analysis of SD content indicated that the genes related to immunity, detoxification, reproduction, and environmental signal recognition are significantly enriched in the silkworm SDs.ConclusionOur results suggested that segmental duplications have been problematic for sequencing and assembling of the silkworm genome. SDs may have important biological significances in immunity, detoxification, reproduction, and environmental signal recognition in the silkworm. This study provides insight into the evolution of the silkworm genome and an invaluable resource for insect genomics research.
| S-EPMC3735471 | biostudies-literature