Methylation perturbations in retroelements within the genome of a Mus interspecific hybrid correlate with double minute chromosome formation

Abstract

A reduction in the DNA modification of cytosine methylation has been linked directly to chromosome rearrangements concomitant with retroelement amplification in several marsupial hybrid genomes. While phenotypes observed for interspecific eutherian hybrids are suggestive of methylation perturbations and retroelement instability, no link between retroelements, DNA methylation, and chromosome instability has yet been identified. Previous studies in eutherian hybrids, however, have been limited to a gross examination of methylation using methylation-sensitive restriction enzyme analysis or focused on single-copy genes and/or have avoided examination of repetitive DNA. Methylation changes and retroelements are proposed as mechanisms for double minute chromosome formation and oncogene amplification, both present in the genome of a Mus hybrid model, thus making it an ideal system to evaluate methylation status more closely. We have used the PCR-based methodologies methylation-sensitive amplicon subtraction (MS-AS) and methylation-sensitive representational difference analysis (MS-RDA) to detect differentially methylated sequences between three complex genomes and to isolate methylation perturbations in a Mus musculusxMus caroli hybrid. This novel application of MS-AS and MS-RDA resulted in the isolation of differentially methylated retroelements surrounding the locus on Chromosome 10 responsible for double minute chromosome formation within this interspecific eutherian hybrid.

Jumping genes and epigenetics: Towards new species

“…Brown et al (2008) Intraspecific crosses of D. melanogaster can result in hybrid dysgenesis, associated with mobilization of P or I elements, dependent on rasiRNA production in the germinal cell line and causing several abnormalities (such as female sterility). Brennecke et al (2008) Crosses between D. buzzatti and D. koepferae activate Osvaldo copies in the hybrid.…”

Chromosome evolution in the subtribe Bovina (Mammalia, Bovidae): The karyotype of the Cambodian banteng (Bos javanicus birmanicus) suggests that Robertsonian translocations are related to interspecific hybridization

“…Bos taurus  Bison bison, Bos taurus  Bos javanicus javanicus (Gray 1972, Steklenev 1997, Nijman et al 2003; (2) female hybrids are less affected by sterility than male hybrids (Orr 1997); (3) Rob translocations are known to occur essentially during oogenesis (Bandyopadhyay et al 2002); (4) interspecific hybrids show genomic instabilities such as chromosome rearrangements chiefly involving the centromere (in particular, centric fusions and wholearm reciprocal translocations), amplification of sequences juxtaposed or integral to the centromere and DNA methylation changes (Shaw et al 1983, Rieseberg et al 1995, O_Neill et al 1998, 2004, Metcalfe et al 2007, Brown et al 2008.…”

Genetic and Epigenetic Changes Involving (Retro)transposons in Animal Hybrids and Polyploids

“…In M. musculus × M. caroli hybrids, fetuses are rarely carried to term, owing to placental dysplasia. The placentas developed in this cross via artificial insemination, despite having a normal karyotype, displayed an anomalous expression of methyltransferases that could be associated with methylation perturbations targeting retrotransposons and with double minute chromosome formation [Brown et al, 2008[Brown et al, , 2012. The placental abnormalities in mouse interspecific hybrids could result from imbalance in DNA methylation as a defense mechanism against genome instability resulting from deregulation of retroelements.…”