Molecular and genomic characterisation of the hybridisation between goat and sheep

• Applicant: Dr. Clemens Falker-Gieske
• Subject Area: Animal Breeding, Animal Nutrition, Animal Husbandry
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 554546015

Hybridisation among mammals is an evolutionary mechanism for species formation (speciation). The occurrence of goat-sheep hybrids is rare, and in most documented cases it involves mating rams with goats. It is speculated that chromosomal incompatibilities hinder overcoming the species barrier. Sheep have 54 chromosomes, while goats have 60 chromosomes. In March 2014, there was a rare birth of a female goat-sheep hybrid with 57 chromosomes, whose parents were a buck and an ewe. Goat-sheep hybrids are generally considered sterile, whereas the case mentioned above succumbed to pregnancy complications in 2018. The quite far developed lamb would technically have been assigned to a new species after successful birth. The preliminary work was based on blood RNA sequencing of the goat-sheep hybrid and its parents. We demonstrated that the imprinting (parent-of-origin effect) pattern of a variety of genes deviated from described patterns, which could have contributed to overcoming species incompatibility. Furthermore, we were able to show that the hybrid suffered from an autoimmune disease caused by the incomplete silencing of so-called barrier loci and immunoglobulin incompatibilities. According to the Dobzhansky-Muller incompatibility model, proteins that interact within a species but not between hybridising species are potential barrier loci. A remarkably large number of genes expressed in the blood of the hybrid from only one parent were immune system genes, whose gene products are known interacting partners. As part of this research project, the genomes of the four individuals - father, mother, goat-sheep hybrid, and its foetus - will be assembled using a combination of long- and short-read sequencing methods. This will provide insight into the genetic mechanisms that enabled overcoming the species barrier. Furthermore, hybrid goat-sheep embryos will be produced through in-vitro fertilization and compared with sheep and goat embryos. This aims to investigate whether deviations in the imprinting of genes already contribute to the emergence of hybrid mammals in the early embryonic stage. For experimental determination of whether autoimmune reactions prevent overcoming the species barrier, embryonic stem cell lines will be generated and differentiated into immune cells. This will clarify the question to what extent the immune incompatibility between goats and sheep contributes to the expression of autoimmune genes. Moreover, this experiment will identify other potential protein-coding barrier loci. The interaction of these proteins will be quantified to prove that they are barrier loci. The knowledge gained will provide insights into the genetic and molecular mechanisms of speciation among mammals, which to date largely rely on theories and assumptions.

• DFG Programme: Research Grants
• Co-Investigators: Professor Dr. Jörn Kalinowski; Professor Dr. Jens Tetens