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.
Abstract.Crosses between two species of the rodent genus Peromyscus produce defects in both growth and development. The defects are pronounced in the hybrid placentas. Peromyscuys maniculatus (strain BW) females mated to P. polionotus (strain PO) males produce placentas half the size of the parental species, as well as growth-retarded embryos. In contrast, PO females mated to BW males result in defective conceptuses that display embryonic and placental overgrowth. These 'parent-of-origin'-dependent phenotypes are consistent with previous studies that demonstrated altered expression of imprinted genes and genetic linkage of the overgrowth phenotypes to imprinted domains. In the present study, we take a broader approach in assessing perturbations in hybrid placental gene expression through the use of Mus musculus cDNA microarrays. In verifying classes of genes identified in microarray screens differentially regulated during hybrid placental development, we focused on those influencing the cell cycle and extracellular matrix (ECM). Our work suggests that cell cycle regulators at the G 1 /S phase check-point are downregulated in the large hybrid placenta, whereas the small hybrid placenta is more variable. The ECM genes are typically downstream targets of cell cycle regulation and their misregulation is consistent with many of the dysmorphic phenotypes. Thus, these data suggest imbalances in proliferation and differentiation in hybrid placentation.
Under conditions of genomic stress, the Mdm locus in human and in mouse is prone to instability manifested as amplification and oncogenesis. The Mdm2 gene is a known oncogene that is amplified in approximately one-third of sarcomas and whose protein product interacts with the tumor suppressor p53. Concimitant with such gene amplification events is the activation and mobilization of endogenous retroelements, typically through the relaxation of epigenetic controlling mechanisms. Processed pseudogenes, which can be formed through endogenous LINE retroelement activity, may indicate increased genomic instability. We have isolated processed pseudogenes for Mdm2 in Mus caroli DNA, likely formed from independent events in different individuals. This is the first identification and characterization of an Mdm2 pseudogene in any organism. Multiple retrotransposition events are suggested by the variable sequence and genomic structure of the identified pseudogenes across all exons and the 3'UTR. The high degree of similarity between the gene and each pseudogene, as well as the lack of evidence for an Mdm2 pseudogene in several other species of Mus, indicate evolutionarily recent retrotransposition events leading to the formation of the Mdm2 pseudogenes in M. caroli. Previous studies on the Mdm2 locus in Mus caroli showed amplification and overexpression of this gene on double minute chromosomes in a Mus musculus x Mus caroli interspecific hybrid. The identification of an Mdm2 retropseudogene within this species further highlights the predisposition to instability for this region of the genome.
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