This cattle pangenome integrates sequences contained in the six individual reference genomes. “This means we can reveal very precisely which sequences are missing, for example, in the Hereford‑based reference genome, but are present in, say, our Brown Swiss genome or the genomes of other cattle breeds and species,” Pausch says.
New genes and functionalities discovered
In this way, the ETH researchers discovered numerous DNA sequences and even whole genes that were missing in the previous reference genome of the Hereford cow. In a further step, the researchers investigated the transcripts of these genes (messenger RNA molecules), which allowed them to classify some of the newly discovered sequences as functionally and biologically relevant. Many of the genes they discovered are connected with immune functions: in animals that had contact with pathogenic bacteria, these genes were stronger or less active than in animals that had no contact with the pathogens.
This project was made possible by a new sequencing technology that has been available at the Functional Genomics Center Zurich for a year now. With this new technology, the researchers are able to precisely read out long DNA sections, reducing the complexity of the computing process needed to correctly assemble the analysed sections. “The new technology simplifies the genome assembly process. Now we can create reference genomes quickly and precisely from scratch,” Pausch says. In addition, such analyses also cost less, meaning that researchers can now generate genomes in reference quality from many individuals of a species.
The ETH researchers are collaborating closely with the Bovine Pangenome Consortium, which wants to create a reference genome of at least one animal from every cattle breed worldwide. It also plans to analyse the genetic makeup of wild relatives of domestic cattle in this way.
More targeted breeding possible
The consortium and ETH professor Pausch hope that the reference genome collection will help them make useful discoveries such as genetic variants that are no longer present in domesticated animals, but that their wild relatives still possess. This would provide clues as to which genetic characteristics were lost as a result of domestication.
“Things get really exciting when we compare our indigenous cattle with the zebu or with breeds that are adapted to other climate conditions,” Pausch explains. This lets researchers find out which genetic variants make animals in tropical environments more heat tolerant. The next step could be to deliberately use crossbreeding to introduce these variants into other cattle breeds or precisely introduce them through genome editing. However, that is still a long way off. For the present, researchers can benefit from the greater speed and precision that the new cattle pangenome brings to the process of detecting the genes and DNA variants that differ between cattle breeds.