Hemoglobin-Gene Cluster Deletions in Antarctic White-Blooded Icefishes Facilitated by Transposable Elements

Vertebrates transport oxygen throughout the body bound to hemoglobin packed in red blood cells. Antarctic icefishes are evolutionary oddities with transparent, white blood lacking hemoglobin. Previous work revealed that the icefish ancestor lost all hemoglobin genes, except for one exon of one alpha-globin gene. This peculiar condition has puzzled biologists for decades and is widely considered maladaptive because it is associated with numerous physiological and anatomical compensations. While we know that hemoglobin genes evolved episodically during cold adaptation in Antarctic notothenioid ancestors and that red-blooded sister species to icefishes have seemingly altered hemoglobin and lack multiple hemoglobin isoforms (hemoglobin multiplicity), we still do not know how the two hemoglobin gene clusters, the LA and MN clusters, shared by all other teleost fishes, were lost in the icefish ancestor. Here, we analyzed the two hemoglobin cluster regions in ten red-blooded notothenioid species and their orthologous region in eight icefishes and identified traces of molecular mechanisms that could have independently deleted each cluster. Adjacent to the LA cluster, an Antarctic notothenioid-specific massive amplification of tRNA genes associated with transposable elements (TEs) likely deleted the hemoglobin cluster when tRNAs transposed into the second intron of the second alpha-globin gene. Independently, extreme species-specific gene turnover characterized the evolution of the MN cluster in all notothenioids. Conserved TEs precisely located at the boundaries of the deleted MN hemoglobin gene cluster incriminate them in the cluster's deletion. Together, these results provide a deeper understanding of the evolution of the iconic icefishes and their unique phenotype.