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Growth and Behaviour: Epigenetic and Genetic Factors Involved in Hybrid Dysgenesis
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In mammals, the most frequently observed hybrid dysgenesis effects are growth disturbances and male sterility. Profound defects in placental development have been described and our work on hybrids in genus Mus has demonstrated putative hybrid dysgenesis effects that lead to defects in lipid homeostasis and maternal behavior. Interestingly, mammalian interspecies hybrids exhibit strong parent-of-origin effects in that offspring of reciprocal matings, even though genetically identical, frequently exhibit reciprocal phenotypes. Recent studies have provided strong link between epigenetic regulation and growth, behavior and placental development. Widespread disruption of genomic imprinting has been described in hybrids between closely related species of the genus Peromyscus. The studies presented in this thesis aim to investigate the effects of disrupted epigenetics states on altered growth, female infanticide and placental dysplasia observed in Mus hybrids. We showed that loss-of-imprinting (LOI) of a paternally expressed gene, Peg1, was correlated with increased body weight of F1 hybrids. Furthermore, we investigated whether LOI of Peg1 in F1 females would interfere with maternal behavior. A subset of F1 females indeed exhibited highly abnormal maternal behavior in that they rapidly attacked and killed the pups. By microarray hybridization, a large number of differentially expressed genes in the infanticidal females as compared to normally behaving females were identified. In addtion to Peg1 LOI, we studied allelic expression of numerous imprinted genes in adult Mus interspecies hybrids. In contrast to the study from Peromyscus, patterns of LOI were not consistent with a direct influence of altered expression levels of imprinted genes on growth. Finally, we investigated the allelic interaction between an X-linked locus and a paternally expressed gene, Peg3, in placental defects in Mus hybrids. This study further strengthened the notion that divergent genetic and epigenetic mechanisms may be involved in hybrid dysgenesis in diverse groups of mammals.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2005. , p. 51
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 11
Keywords [en]
Developmental biology, Interspecies hybridization, hybrid dysgenesis effect, speciation, genomic imprinting, epigenetics
Keywords [sv]
Utvecklingsbiologi
National Category
Developmental Biology
Identifiers
URN: urn:nbn:se:uu:diva-4784ISBN: 91-554-6147-6 (print)OAI: oai:DiVA.org:uu-4784DiVA, id: diva2:165749
Public defence
2005-03-17, Lindahlsalen, Evolutionary Biology Centre, Norbyvägen 18A, Uppsala, 10:00 (English)
Opponent
Supervisors
Available from: 2005-02-14 Created: 2005-02-14 Last updated: 2009-04-05Bibliographically approved
List of papers
1. Loss-of-imprinting of Peg1 in mouse interspecies hybrids is correlated with altered growth
Open this publication in new window or tab >>Loss-of-imprinting of Peg1 in mouse interspecies hybrids is correlated with altered growth
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2004 (English)In: Genesis, ISSN 1526-954X, E-ISSN 1526-968X, Vol. 39, no 1, p. 65-72Article in journal (Refereed) Published
National Category
Developmental Biology
Identifiers
urn:nbn:se:uu:diva-92601 (URN)10.1002/gene.20027 (DOI)
Available from: 2005-02-14 Created: 2005-02-14 Last updated: 2017-12-14Bibliographically approved
2. Female infanticide associated with interspecies hybridization in the genus Mus
Open this publication in new window or tab >>Female infanticide associated with interspecies hybridization in the genus Mus
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(English)Manuscript (Other (popular science, discussion, etc.))
Identifiers
urn:nbn:se:uu:diva-92602 (URN)
Available from: 2005-02-14 Created: 2005-02-14 Last updated: 2010-02-04
3. Widespread disruption of genomic imprinting in adult interspecies mouse (Mus) hybrids
Open this publication in new window or tab >>Widespread disruption of genomic imprinting in adult interspecies mouse (Mus) hybrids
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2005 (English)In: Genesis, ISSN 1526-954X, E-ISSN 1526-968X, Vol. 43, no 3, p. 100-108Article in journal (Refereed) Published
Keywords
Animals, Chimera/*genetics/growth & development, DNA Methylation, Epigenesis; Genetic, Genomic Imprinting, Growth/genetics, Hybridization; Genetic, Mice/*genetics/growth & development, Mice; Congenic/genetics/growth & development, Mice; Inbred C3H, Mice; Inbred C57BL, Research Support; Non-U.S. Gov't
National Category
Developmental Biology
Identifiers
urn:nbn:se:uu:diva-92603 (URN)10.1002/gene.20161 (DOI)16145677 (PubMedID)
Available from: 2005-02-14 Created: 2005-02-14 Last updated: 2017-12-14Bibliographically approved
4. Divergent genetic and epigenetic post-zygotic isolation mechanisms in Mus and Peromyscus
Open this publication in new window or tab >>Divergent genetic and epigenetic post-zygotic isolation mechanisms in Mus and Peromyscus
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2004 (English)In: Journal of Evolutionary Biology, ISSN 1010-061X, E-ISSN 1420-9101, Vol. 17, no 2, p. 453-460Article in journal (Refereed) Published
Abstract [en]

Interspecific hybridization in the rodent genera Peromyscus and Mus results in abnormal placentation. In the Peromyscus interspecies hybrids, abnormal allelic interaction between an X-linked locus and the imprinted paternally expressed Peg3 locus was shown to cause the placental defects. In addition, loss-of-imprinting (LOI) of Peg3 was positively correlated with increased placental size. As in extreme cases this placental dysplasia constitutes a post-zygotic barrier against interspecies hybridization, this finding was the first direct proof that imprinted genes may be important in speciation and thus in evolution. In the Mus interspecies hybrids, a strong role of an X-linked locus in placental dysplasia has also been detected. However, here we show by backcross and allele specific expression analyses that neither LOI of Peg3 nor abnormal interactions between Peg3 and an X-linked locus are involved in generating placental dysplasia in Mus hybrids, although the placental phenotypes observed in the two genera seem to be identical. In contrast to this, another dysgenesis effect common to Peromyscus and Mus hybrids, altered foetal growth, is caused at least in part by the same X-chromosomal regions in both genera. These findings first underline the strong involvement of the X-chromosome in the genetics of speciation. Secondly, they indicate that disruption of epigenetic states, such as LOI, at specific loci may be involved in hybrid dysgenesis effects in one group, but not in another. Thus, we conclude that even in closely related groups divergent molecular mechanisms may be involved in the production of phenotypically similar post-zygotic barriers against hybridization.

National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-92604 (URN)10.1046/j.1420-9101.2003.00656.x (DOI)15009278 (PubMedID)
Available from: 2005-02-14 Created: 2005-02-14 Last updated: 2017-12-14Bibliographically approved

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