Evolutionary context can clarify gene names: Teleosts as a case study

Abstract

We developed an ex silico evolutionary-based systematic synteny approach to define and name the duplicated genes in vertebrates. The first convention for the naming of genes relied on historical precedent, the order in the human genome, and mutant phenotypes in model systems. However, total-genome duplication that resulted in teleost genomes required the naming of duplicated orthologous genes (ohnologs) in a specific manner. Unfortunately, as we review here, such naming has no defined criteria, and some ohnologs and their orthologs have suffered from incorrect nomenclature, thus creating confusion in comparative genetics and disease modeling. We sought to overcome this barrier by establishing an ex silico evolutionary-based systematic approach to naming ohnologs in teleosts. We developed software and compared gene synteny in zebrafish using the spotted gar genome as a reference, representing the unduplicated ancestral state. Using new criteria, we identified several hundred potentially misnamed ohnologs and validated the principle manually.

Genomic analysis of hypoxia inducible factor alpha in ray-finned fishes reveals missing Ohnologs and evidence of widespread positive selection

“…This discrepancy arises because in zebrafish, “the a or b suffix does not indicate primacy of publication and will be assigned purely based on the suffix of the surrounding genes” ( https://zfin.atlassian.net/wiki/spaces/general/overview ). Gasanov et al 59 suggest that this convention lacks phylogenetic context and should be revisited as the syntenic relationships between individual paralogs and ancestral fishes are elucidated, as we have now done for HIF2A . Until there is consensus, however, great care will be needed when interpreting reports of paralog-specific differences in HIF2A .…”

“…The duplication of HIFA genes during the TGD followed by the subsequent lineage-specific loss of various paralogs has given rise to an inconsistent nomenclature. Herein, we adopt two naming conventions that recognize the evolutionary relationships of teleost-specific paralogs 59 . First, when one or more lineage retains both paralogs, the “a” form is the one that shares more flanking genes with the ancestral (gar) form.…”

“…Indeed, the very limited shared gene order between Otocephala HIF3A and HIF3A in other ray-finned fishes suggests that might have occurred for this gene. Without clear evidence of the relationships of the paralogs to the ancestral form, the use of “a” and “b” should be avoided 59 .…”

“…net/ wiki/ spaces/ gener al/ overv iew). Gasanov et al 59 suggest that this convention lacks phylogenetic context and should be revisited as the syntenic relationships between individual paralogs and ancestral fishes are elucidated, as we have now done for HIF2A. Until there is consensus, however, great care will be needed when interpreting reports of paralog-specific differences in HIF2A.…”

Evolution of inwardly rectifying potassium channels and their gene expression in zebrafish embryos

“…Thus, the classification and naming of the Kir genes present a challenging task in the ray‐finned fishes. We suggest careful phylogenic and syntenic analysis should be considered for naming the duplicated genes as Gasanov et al has proposed 40 …”