Gene Loss

Publication Details

Identifier: JB_JR4NRF

Curator: M. Lopes-Marques

DOI: 10.1038/s41598-020-68106-y

PMID: 32665690

Title:

GBA3: a polymorphic pseudogene in humans that experienced repeated gene loss during mammalian evolution.

Abstract:

The gene encoding the cytosolic β-glucosidase GBA3 shows pseudogenization due to a truncated allele (rs358231) that is polymorphic in humans. Since this enzyme is involved in the transformation of many plant β-glycosides, this particular case of gene loss may have been influenced by dietary adaptations during evolution. In humans, apart from the inactivating allele, we found that GBA3 accumulated additional damaging mutations, implying an extensive GBA3 loss. The allelic distribution of loss-of-function alleles revealed significant differences between human populations which can be partially related with their staple diet. The analysis of mammalian orthologs disclosed that GBA3 underwent at least nine pseudogenization events. Most events of pseudogenization occurred in carnivorous lineages, suggesting a possible link to a β-glycoside poor diet. However, GBA3 was also lost in omnivorous and herbivorous species, hinting that the physiological role of GBA3 is not fully understood and other unknown causes may underlie GBA3 pseudogenization. Such possibility relies upon a putative role in sialic acid biology, where GBA3 participates in a cellular network involving NEU2 and CMAH. Overall, our data shows that the recurrent loss of GBA3 in mammals is likely to represent an evolutionary endpoint of the relaxation of selective constraints triggered by diet-related factors.

Last update:

13-06-2024

Associated Glosses (35 results)

GlossID	Species	Symbol	Gene Loss Mechanism	Loss Type	Lineage Specific	Citation
GL_TVCBXL	Trichechus manatus latirostris	GBA3	LOF (frameshift, premature stop, ss)	Full	No	10.1038/s41598-020-68106-y
GL_VEZVKJ	Lipotes vexillifer	GBA3	LOF (frameshift, premature stop, ss)	Full	Cetacea	10.1038/s41598-020-68106-y
GL_WBRFMZ	Desmodus rotundus	GBA3	LOF (frameshift, premature stop, ss)	Full	No	10.1038/s41598-020-68106-y
GL_YKZE9M	Vulpes vulpes	GBA3	LOF (frameshift, premature stop, ss)	Polymorphic	Carnivora	10.1038/s41598-020-68106-y
GL_ZAGWNV	Homo sapiens	GBA3	LOF (frameshift, premature stop, ss)	Polymorphic	No	10.1038/s41598-020-68106-y