Gene Loss

Publication Details

Identifier: JB_FB3AXO

Curator: Inês Ferreira Amorim

Title:

Mx1 and Mx2 key antiviral proteins are surprisingly lost in toothed whales.

Abstract:

Viral outbreaks in dolphins and other Delphinoidea family members warrant investigation into the integrity of the cetacean immune system. The dynamin-like GTPase genes Myxovirus 1 (Mx1) and Mx2 defend mammals against a broad range of viral infections. Loss of Mx1 function in human and mice enhances infectivity by multiple RNA and DNA viruses, including orthomyxoviruses (influenza A), paramyxoviruses (measles), and hepadnaviruses (hepatitis B), whereas loss of Mx2 function leads to decreased resistance to HIV-1 and other viruses. Here we show that both Mx1 and Mx2 have been rendered nonfunctional in Odontoceti cetaceans (toothed whales, including dolphins and orcas). We discovered multiple exon deletions, frameshift mutations, premature stop codons, and transcriptional evidence of decay in the coding sequence of both Mx1 and Mx2 in four species of Odontocetes. We trace the likely loss event for both proteins to soon after the divergence of Odontocetes and Mystocetes (baleen whales) ∼33-37 Mya. Our data raise intriguing questions as to what drove the loss of both Mx1 and Mx2 genes in the Odontoceti lineage, a double loss seen in none of 56 other mammalian genomes, and suggests a hitherto unappreciated fundamental genetic difference in the way these magnificent mammals respond to viral infections.

Last update:

24-03-2025

Associated Glosses (8 results)

GlossID	Species	Symbol	Gene Loss Mechanism	Loss Type	Lineage Specific	Citation
GL_6L5NLO	Lipotes vexillifer	MX2	LOF (frameshift, premature stop, ss)	Full	ODONTOCETI	10.1073/pnas.1501844112
GL_DLEOK8	Lipotes vexillifer	MX1	LOF (frameshift, premature stop, ss)	Full	No	10.1073/pnas.1501844112
GL_E237R1	Physeter catodon	MX2	Exon(s) deletion	Full	ODONTOCETI	10.1073/pnas.1501844112
GL_NBU0EF	Orcinus orca	MX1	Exon(s) deletion	Full	No	10.1073/pnas.1501844112
GL_OQGK4J	Tursiops truncatus	MX2	Exon(s) deletion	Full	ODONTOCETI	10.1073/pnas.1501844112
GL_UBSSFO	Physeter catodon	MX1	LOF (frameshift, premature stop, ss)	Full	No	10.1073/pnas.1501844112
GL_XGNCRD	Orcinus orca	MX2	Exon(s) deletion	Full	ODONTOCETI	10.1073/pnas.1501844112
GL_XOXXS7	Tursiops truncatus	MX1	Exon(s) deletion	Full	No	10.1073/pnas.1501844112