Parent‐of‐origin growth effects and the evolution of hybrid inviability in dwarf hamsters

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 we describe extreme parent-of-origin dependent growth in hybrids from crosses between two species of dwarf hamsters, Phodopus campbelli and P. sungorus. One cross type resulted in massive placental and embryonic overgrowth, severe developmental defects, and maternal death. Embryos from the reciprocal cross were viable and normal sized but adult hybrid males were relatively small. These effects are strikingly similar to patterns from several other mammalian hybrids. Using comparative sequence data from dwarf hamsters and several other hybridizing mammals, we argue that extreme hybrid growth can contribute to reproductive isolation during the early stages of species divergence. Next we tested if abnormal growth in hybrid hamsters was associated with disrupted genomic imprinting. We found no association between imprinting status at several candidate genes and hybrid growth, though two interacting genes involved in embryonic growth did show reduced expression in overgrown hybrids. Collectively, our study indicates that growth-related hybrid inviability may play an important role in mammalian speciation but that the genetic underpinnings of these phenotypes remain unresolved.

Genomic imprinting, disrupted placental expression, and speciation

“…However, it remains unclear if common forms of intrinsic hybrid sterility or inviability often reflect a common genetic basis that is regulatory in nature. Abnormal hybrid growth in mammals is broadly interesting in this context because it is a recurrent and rapidly evolving form of hybrid inviability for which there are strong a priori reasons to suspect a regulatory basis involving genomic imprinting (Brekke and Good ). In our study, we found a strong link between disrupted gene expression, genomic imprinting, and extreme hybrid overgrowth in dwarf hamsters.…”

“…). Mammalian hybrids often show extreme parent‐of‐origin growth effects where reciprocal hybrids differ in size and are either much larger or smaller than the parental species (Vrana ; Brekke and Good ; Wolf et al. ).…”

“…Though there are several potential ways that genomic imprinting could contribute to hybrid incompatibilities (Chakraborty ; Varmuza ; Crespi and Nosil ; Brekke and Good ), speciation research has primarily emphasized the importance of regulatory incompatibilities that cause dosage imbalances within imprinted expression pathways (Vrana ; Wolf et al. ).…”

Interspecific hybrids of dwarf hamsters and Phasianidae birds as animal models for studying the genetic and developmental basis of hybrid incompatibility

“…Notably, biallelic expression of several genes, which contrasts with monoallelic expression of orthologous mouse genes, is observed in hybrids. For example, Grb10, Igr2r and Mash2, whose orthologous mouse genes are expressed maternally, show biallelic expression in the placentas of both reciprocal hybrids (Brekke and Good, 2014; Uno, Y., Ohishi, N., Tsuchiya, K., and Matsuda, Y., unpublished data). It is important to note that whether these genes undergo monoallelic or biallelic expression in parental species remains unclear.…”

“…Notably, parent-of-origin effects are observed in the growth phenotypes of embryos and placentas of the F 1 hybrids, which differ between the cross (P. campbelli females × P. sungorus males) and its reciprocal. In the cross between P. campbelli females and P. sungorus males, embryos and placentas grow normally, but in the reciprocal cross, embryos and placentas exhibit overgrowth (Brekke and Good, 2014; Uno, Y., Ohishi, N., Tsuchiya, K., and Matsuda, Y., unpublished data). The reciprocal cross leads to serious dystocia, which usually results in embryonic death before birth.…”