Year of Award

2016

Document Type

Dissertation

Degree Type

Doctor of Philosophy (PhD)

Other Degree Name/Area of Focus

Biology

Department or School/College

Division of Biological Sciences

Committee Chair

Jeffrey Good

Commitee Members

Doug Emlen, Lila Fishman, John McCutcheon, Paul Vrana

Abstract

Mammalian hybrids often show abnormal growth, indicating that developmental inviability may play an important role in mammalian speciation. Yet it is unclear if this recurrent phenotype reflects a common genetic basis. Here I describe patterns of hybrid inviability between two closely related species of dwarf hamsters, Phodopus campbelli and P. sungorus. Using genetic crosses, I found extreme parent-of-origin dependent growth in hybrid embryos and placentas. Abnormal growth in hybrid mammals has been empirically linked to genomic imprinting, the parent-specific silencing of a single allele that occurs in many genes involved in regulating embryonic growth. Epigenetic disruptions of genomic imprinting activate transcription of the normally silenced allele and are thought to increase expression level. Higher expression of genes whose imprinting is disrupted may cause a dosage imbalance between growth factors and repressors, ultimately leading to abnormal embryonic growth. I next tested the general prediction that disrupted imprinting leads to an increased expression of growth promoting genes in large F1 hybrid hamsters from the genus Phodopus. I found that disrupted imprinting correlates strongly with placental growth and changes in the expression level of imprinted genes, but that widespread disruptions in the silencing of maternally-expressed genes associates with lower, not higher, gene expression. As maternally expressed genes tend to repress offspring growth, these data suggest that overgrowth is associated with a reduced level of growth repressors rather than an excess of growth factors.

Asymmetric hybrid phenotypes imply a genetic basis that is uniparentally inherited, for example the X chromosome, mitochondria, and imprinted genes. Hybrid dwarf hamsters in the genus Phodopus exhibit extreme parent-of-origin growth of both placenta and embryos. Finally, I used a suite of genetic and genomic experiments test whether the X chromosome, the mitochondria, or imprinted genes are involved in parent-of-origin dependent growth in hybrid dwarf hamsters. I demonstrated a major role for the maternally inherited X chromosome, and widespread disruptions of expression of autosomal genes including imprinted genes but no influence of the mitochondria. My data suggest that an incompatible interaction involving the maternally inherited P. sungorus X chromosome and a paternally inherited P. campbelli autosomal element results in placental and embryonic overgrowth. Overgrowth is also correlated with a greatly reduced expression of maternally-expressed imprinted genes, though any connection between expression and the X chromosome remains unclear.

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© Copyright 2016 Thomas David Brekke