Gianni C Ferreri

University of Connecticut, Storrs, CT, United States

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Publications (9)45.53 Total impact

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    ABSTRACT: Mammalian retrotransposons, transposable elements that are processed through an RNA intermediate, are categorized as short interspersed elements (SINEs), long interspersed elements (LINEs), and long terminal repeat (LTR) retroelements, which include endogenous retroviruses. The ability of transposable elements to autonomously amplify led to their initial characterization as selfish or junk DNA; however, it is now known that they may acquire specific cellular functions in a genome and are implicated in host defense mechanisms as well as in genome evolution. Interactions between classes of transposable elements may exert a markedly different and potentially more significant effect on a genome than interactions between members of a single class of transposable elements. We examined the genomic structure and evolution of the kangaroo endogenous retrovirus (KERV) in the marsupial genus Macropus. The complete proviral structure of the kangaroo endogenous retrovirus, phylogenetic relationship among relative retroviruses, and expression of this virus in both Macropus rufogriseus and M. eugenii are presented for the first time. In addition, we show the relative copy number and distribution of the kangaroo endogenous retrovirus in the Macropus genus. Our data indicate that amplification of the kangaroo endogenous retrovirus occurred in a lineage-specific fashion, is restricted to the centromeres, and is not correlated with LINE depletion. Finally, analysis of KERV long terminal repeat sequences using massively parallel sequencing indicates that the recent amplification in M. rufogriseus is likely due to duplications and concerted evolution rather than a high number of independent insertion events.
    Journal of Virology 03/2011; 85(10):4761-71. · 5.08 Impact Factor
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    ABSTRACT: The transcriptional framework of the eukaryotic centromere core has been described in budding yeast and rice, but for most eukaryotes and all vertebrates it remains largely unknown. The lack of large pericentric repeats in the tammar wallaby has made it possible to map and identify the transcriptional units at the centromere in a mammalian species for the first time. We show that these transcriptional units, comprised of satellites and a retrovirus, are bound by centromere proteins and that they are the source of a novel class of small RNA. The endogenous retrovirus from which these small RNAs are derived is now known to be in the centromere domain of several vertebrate classes. The discovery of this new RNA form brings together several independent lines of evidence that point to a conserved retroviral-encoded processed RNA entity within eukaryotic centromeres.
    Chromosoma 11/2008; 118(1):113-25. · 3.34 Impact Factor
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    ABSTRACT: Parent-specific methylation of specific CpG residues is critical to imprinting in eutherian mammals, but its importance to imprinting in marsupials and, thus, the evolutionary origins of the imprinting mechanism have been the subject of controversy. This has been particularly true for the imprinted Insulin-like Growth Factor II (IGF2), a key regulator of embryonic growth in vertebrates and a focal point of the selective forces leading to genomic imprinting. The presence of the essential imprinting effector, DNMT3L, in marsupial genomes and the demonstration of a differentially methylated region (DMR) in the retrotransposon-derived imprinted gene, PEG10, in tammar wallaby argue for a role for methylation in imprinting, but several studies have found no evidence of parent-specific methylation at other imprinted loci in marsupials. We performed the most extensive search to date for allele-specific patterns of CpG methylation within CpG isochores or CpG enriched segments across a 22 kilobase region surrounding the IGF2 gene in the South American opossum Monodelphis domestica. We identified a previously unknown 5'-untranslated exon for opossum IGF2, which is flanked by sequences defining a putative neonatal promoter, a DMR and an active Matrix Attachment Region (MAR). Demethylation of this DMR in opossum neonatal fibroblasts results in abherrant biallelic expression of IGF2. The demonstration of a DMR and an active MAR in the 5' flank of opossum IGF2 mirrors the regulatory features of the 5' flank of Igf2 in mice. However, demethylation induced activation of the maternal allele of IGF2 in opossum differs from the demethylation induced repression of the paternal Igf2 allele in mice. While it can now be concluded that parent-specific DNA methylation is an epigentic mark common to Marsupialia and Eutheria, the molecular mechanisms of transcriptional silencing at imprinted loci have clearly evolved along independent trajectories.
    BMC Genomics 02/2008; 9:205. · 4.40 Impact Factor
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    ABSTRACT: Several lines of evidence suggest that, within a lineage, particular genomic regions are subject to instability that can lead to specific types of chromosome rearrangements important in species incompatibility. Within family Macropodidae (kangaroos, wallabies, bettongs, and potoroos), which exhibit recent and extensive karyotypic evolution, rearrangements involve chiefly the centromere. We propose that centromeres are the primary target for destabilization in cases of genomic instability, such as interspecific hybridization, and participate in the formation of novel chromosome rearrangements. Here we use standard cytological staining, cross-species chromosome painting, DNA probe analyses, and scanning electron microscopy to examine four interspecific macropodid hybrids (Macropus rufogriseus x Macropus agilis). The parental complements share the same centric fusions relative to the presumed macropodid ancestral karyotype, but can be differentiated on the basis of heterochromatic content, M. rufogriseus having larger centromeres with large C-banding positive regions. All hybrids exhibited the same pattern of chromosomal instability and remodeling specifically within the centromeres derived from the maternal (M. rufogriseus) complement. This instability included amplification of a satellite repeat and a transposable element, changes in chromatin structure, and de novo whole-arm rearrangements. We discuss possible reasons and mechanisms for the centromeric instability and remodeling observed in all four macropodid hybrids.
    Genetics 01/2008; 177(4):2507-17. · 4.39 Impact Factor
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    ABSTRACT: Despite abundant examples of both adaptation at the level of phenotype and Darwinian selection at the level of genes, correlations between these two processes are notoriously difficult to identify. Positive Darwinian selection on genes is most easily discerned in cases of genetic conflict, when antagonistic evolutionary processes such as a Red Queen race drive the rate of nonsynonymous substitution above the neutral mutation rate. Genomic imprinting in mammals is thought to be the product of antagonistic evolution coincident with evolution of the placenta, but imprinted loci lack evidence of positive selection likely because of the ancient origin of viviparity in mammals. To determine whether genetic conflict is a general feature of adaptation to placental reproduction, we performed comparative evolutionary analyses of the insulin-like growth factor II (IGF2) gene in teleost fishes. Our analysis included several members of the order Cyprinodontiformes, in which livebearing and placentation have evolved several times independently. We found that IGF2 is subject to positive Darwinian selection coincident with the evolution of placentation in fishes, with particularly strong selection among lineages that have evolved placentation recently. Positive selection is also detected along ancient lineages of placental livebearing fishes, suggesting that selection on IGF2 function is ongoing in placental species. Our observations provide a rare example of natural selection acting in synchrony at the phenotypic and molecular level. These results also constitute the first direct evidence of parent–offspring conflict driving gene evolution.
    Proceedings of the National Academy of Sciences 07/2007; 104(30):12404-12409. · 9.81 Impact Factor
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    ABSTRACT: It has been hypothesized that rapid divergence in centromere sequences accompanies rapid karyotypic change during speciation. However, the reuse of breakpoints coincident with centromeres in the evolution of divergent karyotypes poses a potential paradox. In distantly related species where the same centromere breakpoints are used in the independent derivation of karyotypes, centromere-specific sequences may undergo convergent evolution rather than rapid sequence divergence. To determine whether centromere sequence composition follows the phylogenetic history of species evolution or patterns of convergent breakpoint reuse through chromosome evolution, we examined the phylogenetic trajectory of centromere sequences within a group of karyotypically diverse mammals, macropodine marsupials (wallabies, wallaroos and kangaroos). The evolution of three classes of centromere sequences across nine species within the genus Macropus (including Wallabia) were compared with the phylogenetic history of a mitochondrial gene, Cytochrome b (Cyt b), a nuclear gene, selenocysteine tRNA (TRSP), and the chromosomal histories of the syntenic blocks that define the different karyotype arrangements. Convergent contraction or expansion of predominant satellites is found to accompany specific karyotype rearrangements. The phylogenetic history of these centromere sequences includes the convergence of centromere composition in divergent species through convergent breakpoint reuse between syntenic blocks. These data support the 'library hypothesis' of centromere evolution within this genus as each species possesses all three satellites yet each species has experienced differential expansion and contraction of individual classes. Thus, we have identified a correlation between the evolution of centromere satellite sequences, the reuse of syntenic breakpoints, and karyotype convergence in the context of a gene-based phylogeny.
    Genome biology 02/2007; 8(8):R170. · 10.30 Impact Factor
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    ABSTRACT: The constitution of the centromeric portions of the sex chromosomes of the red-necked wallaby, Macropus rufogriseus (family Macropodidae, subfamily Macropodinae), was investigated to develop an overview of the sequence composition of centromeres in a marsupial genome that harbors large amounts of centric and pericentric heterochromatin. The large, C-band-positive centromeric region of the X chromosome was microdissected and the isolated DNA was microcloned. Further sequence and cytogenetic analyses of three representative clones show that all chromosomes in this species carry a 178-bp satellite sequence containing a CENP-B DNA binding domain (CENP-B box) shown herein to selectively bind marsupial CENP-B protein. Two other repeats isolated in this study localize specifically to the sex chromosomes yet differ in copy number and intrachromosomal distribution. Immunocytohistochemistry assays with anti-CENP-E, anti-CREST, anti-CENP-B, and anti-trimethyl-H3K9 antibodies defined a restricted point localization of the outer kinetochore at the functional centromere within an enlarged pericentric and heterochromatic region. The distribution of these repeated sequences within the karyotype of this species, coupled with the apparent high copy number of these sequences, indicates a capacity for retention of large amounts of centromere-associated DNA in the genome of M. rufogriseus.
    Genetics 03/2006; 172(2):1129-37. · 4.39 Impact Factor
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    ABSTRACT: The centromere is a cytologically defined entity that possesses a conserved and restricted function in the cell: it is the site of kinetochore assembly and spindle attachment. Despite its conserved function, the centromere is a highly mutable portion of the chromosome, carrying little sequence conservation across taxa. This divergence has made studying the movement of a centromere, either within a single karyotype or between species, a challenging endeavor. Several hypotheses have been proposed to explain the permutability of centromere location within a chromosome. This permutability is termed "centromere repositioning" when described in an evolutionary context and "neocentromerization" when abnormalities within an individual karyotype are considered. Both are characterized by a shift in location of the functional centromere within a chromosome without a concomitant change in linear gene order. Evolutionary studies across lineages clearly indicate that centromere repositioning is not a rare event in karyotypic evolution and must be considered when examining the evolution of chromosome structure and syntenic order. This paper examines the theories proposed to explain centromere repositioning in mammals. These theories are interpreted in light of evidence gained in human studies and in our presented data from the marsupial model species Macropus eugenii, the tammar wallaby.
    Journal of Heredity 03/2005; 96(3):217-24. · 2.00 Impact Factor
  • G C Ferreri, M Marzelli, W Rens, R J O'Neill
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    ABSTRACT: Studies of chromosome evolution have focused heavily on the evolution of conserved syntenic, gene-rich domains. It is obvious, however, that the centromere plays an equally important role in chromosome evolution, through its involvement in fissions, centric fusions, translocations, inversions and centric shifts. It is unclear how the centromere, either as a functioning unit of the chromosome or as a DNA sequence motif, has been involved in these processes. Marsupials of the family Macropodidae (kangaroos, wallabies, rat kangaroos and potoroos) offer unique insights into current theories expositing centromere emergence during karyotypic diversification and speciation. Tracing the genomic distribution of centromeric sequences in a model macropodine (subfamily Macropodinae: kangaroos and wallabies) species, Macropus eugenii (tammar wallaby), indicates these sequences have played an important role in chromosome evolution through possible segmental duplications associated with phylogenetically conserved breaks of synteny, pericentromeric and subtelomeric regions. Hybrids between different kangaroo species provide evidence that the centromere is unstable within this group of mammals and is involved in a large number of chromosome aberrations. A better understanding of the genetic and epigenetic factors that define centromeres and how centromeres may mediate changes in chromosome architecture are critical not only to our understanding of basic cellular functioning but also to our understanding of the process of speciation.
    Cytogenetic and Genome Research 02/2004; 107(1-2):115-8. · 1.84 Impact Factor