A preliminary comparative analysis of primate segmental duplications shows elevated substitution rates and a great-ape expansion of intrachromosomal duplications

She, Xinwei; Liu, Ge; Ventura, Mario; Zhao, Shaying; Misceo, Doriana; Roberto, Roberta; Cardone, Maria Francesca; Rocchi, Mariano; Program, Nisc Comparative Sequencing; Green, Eric D.; Archidiacano, Nicoletta; Eichler, Evan E.

doi:10.1101/gr.4949406

Cited by 81 publications

(84 citation statements)

References 42 publications

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“…It is therefore tempting to speculate that hemizogosity of the X chromosome in the male germ line has led to an elevation of intrachromosomal NAHR, as has been observed for the duplications that mediate the inversion that causes factor VIII deficiency (27). Indeed, gene conversion is thought to be a key mechanism for the long-term survival of genes on the Y chromosome (36), and both the human X and Y chromosomes have a disproportionately high percentage of intrachromosomal duplications with Ͼ99% identity (30,31) and inverted repeats (37). A second possibility is that it is not the retention of the duplications that is being selected for, but the ability to alter the orientation of the inverted region, which may have some unknown beneficial consequence.…”

Section: Discussionmentioning

confidence: 99%

“…With regard to the evolution of the duplications, it has been argued that gene conversion is not prevalent enough to obscure the true age of most duplications in the human genome, and near-identical duplications are likely to have arisen in the very recent past and be species-or clade-specific (29,30). In contrast to this assertion, our detailed sequence analysis of the duplications flanking the FLNA-EMD region is consistent with the action of gene conversion and suggests a single origin for the duplications common to all eutherians, thereby dating the duplication to a time point Ͼ100 million years ago.…”

Section: Discussionmentioning

confidence: 99%

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A recurrent inversion on the eutherian X chromosome

Cáceres

Sullivan

Thomas

2007

Proc. Natl. Acad. Sci. U.S.A.

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Chromosomal inversions have an important role in evolution, and an increasing number of inversion polymorphisms are being identified in the human population. The evolutionary history of these inversions and the mechanisms by which they arise are therefore of significant interest. Previously, a polymorphic inversion on human chromosome Xq28 that includes the FLNA and EMD loci was discovered and hypothesized to have been the result of nonallelic homologous recombination (NAHR) between near-identical inverted duplications flanking this region. Here, we carried out an in-depth study of the orthologous region in 27 additional eutherians and report that this inversion is not specific to humans, but has occurred independently and repeatedly at least 10 times in multiple eutherian lineages. Moreover, inverted duplications flank the FLNA-EMD region in all 16 species for which high-quality sequence assemblies are available. Based on detailed sequence analyses, we propose a model in which the observed inverted duplications originated from a common duplication event that predates the eutherian radiation. Subsequent gene conversion homogenized the duplications, thereby providing a continuous substrate for NAHR that led to the recurrent inversion of this segment of the genome. These results provide an extreme example in support of the evolutionary breakpoint reusage hypothesis and point out that some near-identical human segmental duplications may, in fact, have originated >100 million years ago.duplication ͉ gene conversion ͉ inversion polymorphism C hromosomal rearrangements were among the first types of genetic variation to be studied and have been proposed to play an important role in genome evolution and the phenotypic differences within and between species (1, 2). The recent availability of genomic data from multiple species has led to the unexpected discovery that structural variation, including inversions, is relatively common in the human population (3, 4), as well as between closely related species, such as human and chimpanzee (5-7). Comparisons of the positions of evolutionary breakpoints in different mammalian lineages suggest that a small fraction of the mammalian genome is particularly prone to rearrangement and constitute breakpoint ''hotspots'' that have been reused over the course of mammalian evolution (e.g., refs. 8 and 9). Therefore, a conserved property of mammalian genomes appears to be the presence of a limited number of fragile regions that commonly mediate chromosomal rearrangements. This observation contrasts with the long-held view that evolutionary breakpoints are distributed randomly across the genome (10), and there has been considerable debate pitting the random breakage model versus the fragile breakage/breakpoint reusage hypothesis (11).One mechanism known to mediate chromosomal rearrangements is nonallelic recombination between homologous sequences (NAHR). In humans, 5% of the genome is comprised of segmental duplications, which are typically defined as duplications Ͼ1 kb in length and Ͼ90% ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A recurrent inversion on the eutherian X chromosome

Cáceres

Sullivan

Thomas

2007

Proc. Natl. Acad. Sci. U.S.A.

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“…described previously . In total, we examined 51 loci (5.0 Mb) for human-chimpanzee, 42 loci (5.0 Mb) for humanbaboon, 45 loci (4.0 Mb) for human-marmoset, and 29 loci (2.8 Mb) for human-lemur genomic sequence alignments (She et al 2006). Large gaps (>100 bp) in these pairwise alignments were subdivided into one of two categories based on their association with a repeat sequence as described previously .…”

Section: Methodsmentioning

confidence: 99%

“…As a second source of data, we constructed optimal global sequence alignments between finished nonhuman primate genomic BAC clones and the human genome reference sequence using previously described methods She et al 2006). We generated a total of 51 human-chimpanzee, 42 human-baboon, 45 human-marmoset, and 29 human-lemur genomic alignments (Table 1; http://bfgl.anri.barc.usda.gov/Alusite).…”

Section: Characterization Of Lineage-specific Alu Repeat Elements Fromentioning

confidence: 99%

Comparative analysis of Alu repeats in primate genomes

Liu¹,

Alkan²,

Lu³

et al. 2009

Genome Res.

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Using bacteria artificial chromosome (BAC) end sequences (16.9 Mb) and high-quality alignments of genomic sequences (17.4 Mb), we performed a global assessment of the divergence distributions, phylogenies, and consensus sequences for Alu elements in primates including lemur, marmoset, macaque, baboon, and chimpanzee as compared to human. We found that in lemurs, Alu elements show a broader and more symmetric sequence divergence distribution, suggesting a steady rate of Alu retrotransposition activity among prosimians. In contrast, Alu elements in anthropoids show a skewed distribution shifted toward more ancient elements with continual declining rates in recent Alu activity along the hominoid lineage of evolution. Using an integrated approach combining mutation profile and insertion/deletion analyses, we identified nine novel lineage-specific Alu subfamilies in lemur (seven), marmoset (one), and baboon/macaque (one) containing multiple diagnostic mutations distinct from their human counterparts-Alu J, S, and Y subfamilies, respectively. Among these primates, we show that that the lemur has the lowest density of Alu repeats (55 repeats/Mb), while marmoset has the greatest abundance (188 repeats/Mb). We estimate that ;70% of lemur and 16% of marmoset Alu elements belong to lineage-specific subfamilies. Our analysis has provided an evolutionary framework for further classification and refinement of the Alu repeat phylogeny. The differences in the distribution and rates of Alu activity have played an important role in subtly reshaping the structure of primate genomes. The functional consequences of these changes among the diverse primate lineages over such short periods of evolutionary time are an important area of future investigation.

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“…CNDs differ from copy number variants (CNVs) (6)(7)(8)(9)(10), in that the former refers to interspecies variation, whereas the latter refers to intraspecies variation. Certain CNDs may have evolved under positive selection in primates (11)(12)(13)(14)(15)(16). Furthermore, CNDs that overlap genes and nongenic regulatory elements can lead to divergent expression profiles and affect phenotypes.…”

mentioning

confidence: 99%

Regulatory element copy number differences shape primate expression profiles

Iskow

Gökçümen

Abyzov

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Gene expression differences are shaped by selective pressures and contribute to phenotypic differences between species. We identified 964 copy number differences (CNDs) of conserved sequences across three primate species and examined their potential effects on gene expression profiles. Samples with copy number different genes had significantly different expression than samples with neutral copy number. Genes encoding regulatory molecules differed in copy number and were associated with significant expression differences. Additionally, we identified 127 CNDs that were processed pseudogenes and some of which were expressed. Furthermore, there were copy number-different regulatory regions such as ultraconserved elements and long intergenic noncoding RNAs with the potential to affect expression. We postulate that CNDs of these conserved sequences fine-tune developmental pathways by altering the levels of RNA.

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A preliminary comparative analysis of primate segmental duplications shows elevated substitution rates and a great-ape expansion of intrachromosomal duplications

Cited by 81 publications

References 42 publications

A recurrent inversion on the eutherian X chromosome

A recurrent inversion on the eutherian X chromosome

Comparative analysis of Alu repeats in primate genomes

Regulatory element copy number differences shape primate expression profiles

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