GBA3: a polymorphic pseudogene in humans that experienced repeated gene loss during mammalian evolution
| Autor: | Renato Salazar, Maria João Prata, Susana Seixas, Ana Rita Cardoso, Mónica Lopes-Marques, Luísa Azevedo, Catarina Serrano, António Amorim |
|---|---|
| Přispěvatelé: | Instituto de Investigação e Inovação em Saúde |
| Rok vydání: | 2020 |
| Předmět: |
0106 biological sciences
0301 basic medicine Mixed Function Oxygenases / genetics Population genetics Evolution Pseudogene lcsh:Medicine Neuraminidase / genetics Neuraminidase Evolutionary biology Biology 010603 evolutionary biology 01 natural sciences Article Evolutionary genetics Mixed Function Oxygenases Evolution Molecular NEU2 beta-Glucosidase / genetics 03 medical and health sciences chemistry.chemical_compound Loss of Function Mutation GBA3 Phylogenetics Genetics Animals Humans Glycosides Loss of Function Mutation / genetics Allele lcsh:Science Gene Phylogeny Mammals Multidisciplinary Glycosides / genetics beta-Glucosidase lcsh:R Glycosides / metabolism Evolution of mammals N-Acetylneuraminic Acid Sialic acid 030104 developmental biology chemistry N-Acetylneuraminic Acid / genetics Molecular evolution lcsh:Q Gene Deletion |
| Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-14 (2020) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-68106-y |
| Popis: | The gene encoding the cytosolic ß-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 ß-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 ß-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. This work was supported by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia, in the framework of the Project POCI-01–0145-FEDER-007274 to i3S and by FCT research Project POCI-01–0145-FEDER-29723. CS holds FCT PhD fellowship (SFRH/BD/137925/2018). ARC holds FCT PhD fellowship (SFRH/BD/141702/2018). Funders had no role in the design, collection, analysis, interpretation of the data, and writing of the manuscript. The authors would like to thank the reviewers for their comments and suggestions. |
| Databáze: | OpenAIRE |
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