Molecular genetic characterization of a buck-ewe hybrid (geep), its parents and offspring

Mammal hybridization is a speciation mechanism and an evolutionary driver. It occurs at so-called hybrid zones, where phylogenetically related species come into contact. Most hybrid animals are sterile, which is caused by chromosomal incompatibilities of the parental genomes. This leads to failure of gamete formation during meiosis, which is most likely caused by divergent evolution leading to different genetic structural variation patterns between closely related species. In the special case of goat-sheep hybrid embryos, haemolytic disease caused by an immune reaction of the mother against fetal red blood cells has been identified to prevent the development of hybrid embryos. In the rare case of successful conception by a hybrid, the resulting offspring is considered a new species, which makes hybrid speciation a mechanism of evolution. Goat-sheep, especially buck-ewe hybrids, are very rare with only one case reported in 2016, which is the subject of the work presented here. The geep under investigation was born near Göttingen (Lower Saxony, Germany) in March 2014 as the result of the mating between a buck and a ewe. The geep died in 2018 due to polyhydramnios during pregnancy. It was pregnant with two fetuses at advanced developmental stages. The cytogenetics of the geep revealed that it had an intermediate karyotype of 57 chromosomes, whereas the buck had 60 and the ewe 54 chromosomes. An in-depth analysis of the blood transcriptomes of the geep and its parents revealed abnormal imprinting patterns, which we concluded is a compensation mechanism for disadvantageous alleles. We found parent-of-origin-specific expression of genes that functionally clustered, which we explain with the Dobzhansky–Muller incompatibility (DMI) model. According to the DMI model, proteins which interact have a high probability of being barrier loci and hence are prone to monoallelic expression. We discovered enrichment of genes uniquely expressed by the buck-ewe hybrid, which implicate that it suffered from an NF-κB lymphoproliferative autoimmune disorder. Similar findings were reported in the F1 generation of hybrid mice. We propose that hybridization of two related species may lead to an autoimmune phenotype, due to immunoglobulin incompatibilities and incomplete silencing of barrier loci. Future studies will focus on the genome assembly of the buck-ewe hybrid, its parents and the fetus.

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