Organization and Evolution of Primate Centromeric DNA from Whole-Genome Shotgun Sequence Data

The major DNA constituent of primate centromeres is alpha satellite DNA. As much as 2%–5% of sequence generated as part of primate genome sequencing projects consists of this material, which is fragmented or not assembled as part of published genome sequences due to its highly repetitive nature. Here, we develop computational methods to rapidly recover and categorize alpha-satellite sequences from previously uncharacterized whole-genome shotgun sequence data. We present an algorithm to computationally predict potential higher-order array structure based on paired-end sequence data and then experimentally validate its organization and distribution by experimental analyses. Using whole-genome shotgun data from the human, chimpanzee, and macaque genomes, we examine the phylogenetic relationship of these sequences and provide further support for a model for their evolution and mutation over the last 25 million years. Our results confirm fundamental differences in the dispersal and evolution of centromeric satellites in the Old World monkey and ape lineages of evolution

Evolutionary History of Chromosome 20

The evolutionary history of human chromosome 20 in primates was investigated using a panel of human BAC/PAC probes spaced along the chromosome. Oligonucleotide primers derived from the sequence of each human clone were used to screen horse, cat, pig, and black lemur BAC libraries to assemble, for each species, a panel of probes mapping to chromosomal loci orthologous to the loci encompassed by the human BACs. This approach facilitated marker-order comparison aimed at defining marker arrangement in primate ancestor. To this goal, we also took advantage of the mouse and rat draft sequences. The almost perfect colinearity of chromosome 20 sequence in humans and mouse could be interpreted as evidence that their form was ancestral to primates. Contrary to this view, we found that horse, macaque, and two New World monkeys share the same marker-order arrangement from which the human and mouse forms can be derived, assuming similar but distinct inversions that fully account for the small difference in marker arrangement between humans and mouse. The evolutionary history of this chromosome unveiled also two centromere repositioning events in New World monkey species

Evolutionary history of chromosome 11 featuring four distinct centromere repositioning events in Catarrhini.

Abstract Panels of BAC clones used in FISH experiments allow a detailed definition of chromosomal marker arrangement and orientation during evolution. This approach has disclosed the centromere repositioning phenomenon, consisting in the activation of a novel, fully functional centromere in an ectopic location, concomitant with the inactivation of the old centromere. In this study, appropriate panels of BAC clones were used to track the chromosome 11 evolutionary history in primates and nonprimate boreoeutherian mammals. Chromosome 11 synteny was found to be highly conserved in both primate and boreoeutherian mammalian ancestors. Amazingly, we detected four centromere repositioning events in primates (in Old World monkeys, in gibbons, in orangutans, and in the Homo–Pan–Gorilla (H-P-G) clade ancestor), and one in Equidae. Both H-P-G and Lar gibbon novel centromeres were flanked by large duplicons with high sequence similarity. Outgroup species analysis revealed that this duplicon was absent in phylogenetically more distant primates. The chromosome 11 ancestral centromere was probably located near the HSA11q telomere. The domain of this inactivated centromere, in humans, is almost devoid of segmental duplications. An inversion occurred in chromosome 11 in the common ancestor of H-P-G. A large duplicon, again absent in outgroup species, was found located adjacent to the inversion breakpoints. In Hominoidea, almost all the five largest duplicons of this chromosome appeared involved in significant evolutionary architectural changes

Inversion variants in human and primate genomes

For many years, inversions have been proposed to be a direct driving force in speciation since they suppress recombination when heterozygous. Inversions are the most common large-scale differences among humans and great apes. Nevertheless, they represent large events easily distinguishable by classical cytogenetics, whose resolution, however, is limited. Here, we performed a genome-wide comparison between human, great ape, and macaque genomes using the net alignments for the most recent releases of genome assemblies. We identified a total of 156 putative inversions, between 103 kb and 91 Mb, corresponding to 136 human loci. Combining literature, sequence, and experimental analyses, we analyzed 109 of these loci and found 67 regions inverted in one or multiple primates, including 28 newly identified inversions. These events overlap with 81 human genes at their breakpoints, and seven correspond to sites of recurrent rearrangements associated with human disease. This work doubles the number of validated primate inversions larger than 100 kb, beyond what was previously documented. We identified 74 sites of errors, where the sequence has been assembled in the wrong orientation, in the reference genomes analyzed. Our data serve two purposes: First, we generated a map of evolutionary inversions in these genomes representing a resource for interrogating differences among these species at a functional level; second, we provide a list of misassembled regions in these primate genomes, involving over 300 Mb of DNA and 1978 human genes. Accurately annotating these regions in the genome references has immediate applications for evolutionary and biomedical studies on primates

Centromere remodeling in Hoolock leuconedys (Hylobatidae) by a new transposable element unique to the gibbons

Gibbons (Hylobatidae) shared a common ancestor with the other hominoids only 15-18 million years ago. Nevertheless, gibbons show very distinctive features that include heavily rearranged chromosomes. Previous observations indicate that this phenomenon may be linked to the attenuated epigenetic repression of transposable elements (TEs) in gibbon species. Here we describe the massive expansion of a repeat in almost all the centromeres of the eastern hoolock gibbon (Hoolock leuconedys). We discovered that this repeat is a new composite TE originating from the combination of portions of three other elements (L1ME5, AluSz6, and SVA-A) and thus named it LAVA. We determined that this repeat is found in all the gibbons but does not occur in other hominoids. Detailed investigation of 46 different LAVA elements revealed that the majority of them have target site duplications (TSDs) and a poly-A tail, suggesting that they have been retrotransposing in the gibbon genome. Although we did not find a direct correlation between the emergence of LAVA elements and human-gibbon synteny breakpoints, this new composite transposable element is another mark of the great plasticity of the gibbon genome. Moreover, the centromeric expansion of LAVA insertions in the hoolock closely resembles the massive centromeric expansion of the KERV-1 retroelement reported for wallaby (marsupial) interspecific hybrids. The similarity between the two phenomena is consistent with the hypothesis that evolution of the gibbons is characterized by defects in epigenetic repression of TEs, perhaps triggered by interspecific hybridization. © 2012 The Author(s)

Using a Pericentromeric Interspersed Repeat to Recapitulate the Phylogeny and Expansion of Human Centromeric Segmental Duplications

Despite considerable advances in sequencing of the human genome over the past few years, the organization and evolution of human pericentromeric regions have been difficult to resolve. This is due, in part, to the presence of large, complex blocks of duplicated genomic sequence at the boundary between centromeric satellite and unique euchromatic DNA. Here, we report the identification and characterization of an approximately 49-kb repeat sequence that exists in more than 40 copies within the human genome. This repeat is specific to highly duplicated pericentromeric regions with multiple copies distributed in an interspersed fashion among a subset of human chromosomes. Using this interspersed repeat (termed PIR4) as a marker of pericentromeric DNA, we recovered and sequence-tagged 3 Mb of pericentromeric DNA from a variety of human chromosomes as well as nonhuman primate genomes. A global evolutionary reconstruction of the dispersal of PIR4 sequence and analysis of flanking sequence supports a model in which pericentromeric duplications initiated before the separation of the great ape species (>12 MYA). Further, analyses of this duplication and associated flanking duplications narrow the major burst of pericentromeric duplication activity to a time just before the divergence of the African great ape and human species (5 to 7 MYA). These recent duplication exchange events substantially restructured the pericentromeric regions of hominoid chromosomes and created an architecture where large blocks of sequence are shared among nonhomologous chromosomes. This report provides the first global view of the series of historical events that have reshaped human pericentromeric regions over recent evolutionary time

The common marmoset genome provides insight into primate biology and evolution

We report the whole-genome sequence of the common marmoset (Callithrix jacchus). The 2.26-Gb genome of a female marmoset was assembled using Sanger read data (6×) and a whole-genome shotgun strategy. A first analysis has permitted comparison with the genomes of apes and Old World monkeys and the identification of specific features that might contribute to the unique biology of this diminutive primate, including genetic changes that may influence body size, frequent twinning and chimerism. We observed positive selection in growth hormone/insulin-like growth factor genes (growth pathways), respiratory complex I genes (metabolic pathways), and genes encoding immunobiological factors and proteases (reproductive and immunity pathways). In addition, both protein-coding and microRNA genes related to reproduction exhibited evidence of rapid sequence evolution. This genome sequence for a New World monkey enables increased power for comparative analyses among available primate genomes and facilitates biomedical research application. © 2014 Nature America, Inc

Alu insertion polymorphisms shared by Papio baboons and Theropithecus gelada reveal an intertwined common ancestry

© 2019 The Author(s). Background: Baboons (genus Papio) and geladas (Theropithecus gelada) are now generally recognized as close phylogenetic relatives, though morphologically quite distinct and generally classified in separate genera. Primate specific Alu retrotransposons are well-established genomic markers for the study of phylogenetic and population genetic relationships. We previously reported a computational reconstruction of Papio phylogeny using large-scale whole genome sequence (WGS) analysis of Alu insertion polymorphisms. Recently, high coverage WGS was generated for Theropithecus gelada. The objective of this study was to apply the high-Throughput poly-Detect method to computationally determine the number of Alu insertion polymorphisms shared by T. gelada and Papio, and vice versa, by each individual Papio species and T. gelada. Secondly, we performed locus-specific polymerase chain reaction (PCR) assays on a diverse DNA panel to complement the computational data. Results: We identified 27,700 Alu insertions from T. gelada WGS that were also present among six Papio species, with nearly half (12,956) remaining unfixed among 12 Papio individuals. Similarly, each of the six Papio species had species-indicative Alu insertions that were also present in T. gelada. In general, P. kindae shared more insertion polymorphisms with T. gelada than did any of the other five Papio species. PCR-based genotype data provided additional support for the computational findings. Conclusions: Our discovery that several thousand Alu insertion polymorphisms are shared by T. gelada and Papio baboons suggests a much more permeable reproductive barrier between the two genera then previously suspected. Their intertwined evolution likely involves a long history of admixture, gene flow and incomplete lineage sorting