Genetic and epigenetic incompatibilities underlie hybrid dysgenesis in peromyscus

TY - JOUR

T1 - Genetic and epigenetic incompatibilities underlie hybrid dysgenesis in peromyscus

AU - Vrana, Paul B.

AU - Fossella, John A.

AU - Matteson, Paul

AU - Del Rio, Tony

AU - O'Neill, Michael J.

AU - Tilghman, Shirley M.

N1 - Funding Information: We thank W. Dawson for advice on Peromyscus and support, and R.S. Ingram for DNA sequencing. This work was supported by a grant from the NIGMS (GM51460). S.M.T. is an Investigator of the Howard Hughes Medical Institute.

PY - 2000/5

Y1 - 2000/5

N2 - 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.

AB - 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.

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U2 - 10.1038/75518

DO - 10.1038/75518

M3 - Article

C2 - 10802670

SN - 1061-4036

VL - 25

SP - 120

EP - 124

JO - Nature genetics

JF - Nature genetics

IS - 1

ER -