Genome editing for "breeding-back" the aurochs

Traditional “breeding-back” takes a long time until satisfying results are achieved, also because cattle are a comparably slow-reproducing species. Also, “breeding-back” cannot revive the aurochs for several reasons, it can merely produce an imitation of the wildtype. That is why many dream of using genome-editing in modern “breeding-back” projects. Genome editing using the CRISPR-Cas9 method enables to cut and modify the genome of an organism, and to insert or exchange alleles in the genome. The now-dead Uruz Project (which now only exists on Wikipedia) started with the claim that they want to use genome editing for “breeding-back” in order to speed up the process. It sounded great, but there are some obstacles. 

First of all, only a handful of genes responsible for the phenotypic characters of interest in cattle have been resolved. For example, we know that a brindle coat colour is caused by a dominant allele on the Agouti locus, that the polled condition is caused by a dominant allele on the Polled locus, and the three alleles on the Extension locus and aggression in cattle is probably influenced by the MAOA locus (go here). But we have no clue which alleles are responsible for horn size or curvature, the various colour dilutions we see in Podolian cattle and Chianina (which are used in “breeding-back”), the size of the hump, the sexual dichromatism and many other traits. And some traits, such as body size, proportions and other morphological traits (which make up the most important differences between cattle and aurochs) are likely controlled by hundreds of genes or even more (cattle have 22.000 genes). Therefore, a lot of research would have to be done in order to use genome editing efficiently for “breeding-back” an imitation of the aurochs. 

Genetic linkage is kind of an argument pro and contra genome editing in “breeding-back” at the same time. It is possible that some morphological/optical aurochs-like traits are linked to wildtype traits with other functions (for example immunological, developmental, physiological). If the wildtype allele(s) for a certain morphological trait is inserted into another genome with genome editing instead of being introduced with traditional breeding, the wildtype allele for non-visible characteristics would not be transferred to the new genome. This is a scenario where genome editing would not be beneficial for the goal (to have as much wildtype alleles as possible) and where traditional breeding would be more effective. However, the opposite scenario would be equally as likely, that some wildtype alleles are genetically linked with domestic alleles on the same chromosome. If the wildtype allele and the domestic allele lie close together on the chromosome, it is not only impossible to get rid of the domestic allele without also losing the wildtype allele but it is also very unlikely that the linkage is ended by recombination. In this case, genome editing would be beneficial: the domestic allele could be cut out and replaced with a wildtype allele from the same locus from another cattle breed that still has the wildtype allele. This is the scenario where genome editing would be highly beneficial for “breeding-back”, and I believe this is what the Uruz Project was referring to when they said they want to use this technique. However, as outlined above, as long as the alleles responsible for the phenotypic traits of relevance, it is not possible to use genome editing for “breeding-back” effectively. 

This is where the fully resolved aurochs genome that was resolved in 2015 from a British Neolithic aurochs bull comes into play. So far, no particular gene has been identified that played a considerable role in the domestication of the aurochs. In horses, two such genes have been identified: one influencing the ability of the animals to bear weight on their back, and one influencing fear response and docility (here). If the same work was done for the aurochs, one could take these genes in the genome of modern cattle (preferably cattle that are already aurochs-like, not Holstein-Frisian) and replace their domestic alleles on these important loci and replace them with alleles taken from the aurochs individual. It has also been found that zebus have some wildtype alleles that were replaced by domestic alleles in domestic cattle (here). These could also be replaced by aurochs alleles in an aurochs-like cattle individual. This modification of the genotype of an already aurochs-like taurine cattle individual would be a reintroduction of organismic wildtype traits that could be very beneficial for the cattle’s survival in nature under natural selection (be it immunological, developmental, physiological, genomic by the removal of deleterious domestic alleles, morphological or behavioural). 

I think it might be possible (though more effortful) to go one step further: replacing all the domestic allele of an aurochs-like taurine cattle individual with those of the aurochs. The result would basically be a recreated aurochs. It would not be a recreation of the original genetic diversity of the wildtype, but at least one individual. As an aurochs enthusiast, I would of course love this scenario. But if that is not possible for technical reasons, even the reintroduction of single wildtype alleles that are lost in modern cattle would already be a success. I really hope that someone one day is going to try it (what would require the “the aurochs can be bred back anyway” mentality to finally disappear).