Synteny and Phylogeny in Name Changes: Principles and Consequences for Gene Orthologies and Paralogies

We agree with McCarthy et al.1 that for name revisions, the benefits should outweigh the risks. It is important that names do not create false expectations, because we believe that they have a powerful influence on the experiments and the way in which we think. It is often noted that the binding of oxytocin to the vasopressin system is surprising and could be avoided if there was a name that reflected their common origin. This knowledge will also be useful for medicine, so that physicians are more aware of drug interactions between the two receptor families. Similarly, in other gene families, McCarthy et al.1 endorse a nomenclature that differs in orthologous genes with a different function across species. For example, the CSAD gene is named ‘cysteine sulfinic acid decarboxylase’ in all species except chickens, in which it is called ‘cysteine acid decarboxylase’. If sequence and or function changes were routinely used to change genes, they would all have different names.

Synteny-based approaches give better resolution for gene orthologies and paralogies, and hence for gene nomenclature, in most cases. Wherever available, we propose using chromosome-scale genomes that are highly contiguous and have a high base-call accuracy2. When synteny is not clear, we suggest that priority is given to nucleotide phylogenetic inference with the same prerequisites for genome quality. The suggested practices for synteny and phylogenetic analyses are provided in the Supplementary Note 5. A universal gene nomenclature is supported by a combination of synteny and highly supported phylogeny.

One possible principle would be to create one committee per major clan, and group these as subcommittees under one large committee for all species of the animal kingdom. Changes would likely be required in infrastructure and the way systems operate, both of which are high-quality.