title: Genetic and epigenetic incompatibilities underlie hybrid dysgenesis in Peromyscus.
abstract: Crosses between the two North American rodent species Peromyscus polionotus (PO) and Peromyscus maniculatus (BW) yield parent-of-origin effects on both embryonic and placental growth. The two species are approximately the same size, but a female BW crossed with a male PO produces offspring that are smaller than either parent. In the reciprocal cross, the offspring are oversized and typically die before birth. Rare survivors are exclusively female, consistent with Haldane's rule, which states that in instances of hybrid sterility or inviability, the heterogametic sex tends to be more severely affected. To understand these sex- and parent-of-origin-specific patterns of overgrowth, we analysed reciprocal backcrosses. Our studies reveal that hybrid inviability is partially due to a maternally expressed X-linked PO locus and an imprinted paternally expressed autosomal BW locus. In addition, the hybrids display skewing of X-chromosome inactivation in favour of the expression of the BW X chromosome. The most severe overgrowth is accompanied by widespread relaxation of imprinting of mostly paternally expressed genes. Both genetic and epigenetic mechanisms underlie hybrid inviability in Peromyscus and hence have a role in the establishment and maintenance of reproductive isolation barriers in mammals.
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: P B
authors.initials: PB
authors.lastname: Vrana
authors.forename: J A
authors.initials: JA
authors.lastname: Fossella
authors.forename: P
authors.initials: P
authors.lastname: Matteson
authors.forename: T
authors.initials: T
authors.lastname: del Rio
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Neill
authors.forename: S M
authors.initials: SM
authors.lastname: Tilghman
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005260:Female; D005328:Fetal Viability / Q000235:genetics; D005718:Gametogenesis / Q000235:genetics; D006059:Gonadal Dysgenesis / Q000235:genetics*; D006824:Hybridization, Genetic / Q000235:genetics*; D008297:Male; D010542:Peromyscus / Q000196:embryology* / Q000235:genetics* / Q000254:growth & development; D012737:Sex Factors