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Since this enzyme is involved in the transformation of many plant \u03b2-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 <jats:italic>GBA3<\/jats:italic> accumulated additional damaging mutations, implying an extensive <jats:italic>GBA3<\/jats:italic> 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 <jats:italic>GBA3<\/jats:italic> underwent at least nine pseudogenization events. Most events of pseudogenization occurred in carnivorous lineages, suggesting a possible link to a \u03b2-glycoside poor diet. However, <jats:italic>GBA3<\/jats:italic> 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 <jats:italic>GBA3<\/jats:italic> 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 <jats:italic>GBA3<\/jats:italic> in mammals is likely to represent an evolutionary endpoint of the relaxation of selective constraints triggered by diet-related factors.<\/jats:p>","DOI":"10.1038\/s41598-020-68106-y","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T10:04:51Z","timestamp":1594721091000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["GBA3: a polymorphic pseudogene in humans that experienced repeated gene loss during mammalian evolution"],"prefix":"10.1038","volume":"10","author":[{"given":"Monica","family":"Lopes-Marques","sequence":"first","affiliation":[]},{"given":"Catarina","family":"Serrano","sequence":"additional","affiliation":[]},{"given":"Ana R.","family":"Cardoso","sequence":"additional","affiliation":[]},{"given":"Renato","family":"Salazar","sequence":"additional","affiliation":[]},{"given":"Susana","family":"Seixas","sequence":"additional","affiliation":[]},{"given":"Ant\u00f3nio","family":"Amorim","sequence":"additional","affiliation":[]},{"given":"Luisa","family":"Azevedo","sequence":"additional","affiliation":[]},{"given":"Maria J.","family":"Prata","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2020,7,14]]},"reference":[{"key":"68106_CR1","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrg.2016.39","volume":"17","author":"R Albalat","year":"2016","unstructured":"Albalat, R. & Ca\u00f1estro, C. 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