i3S- Instituto de Investigação e Inovação em Saúde, Population Genetics and Evolution Group, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal.
IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal.
Sci Rep. 2020 Jul 14;10(1):11565. doi: 10.1038/s41598-020-68106-y.
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.
编码细胞质β-葡萄糖苷酶 GBA3 的基因由于存在多态性的截断等位基因（rs358231）而发生假基因化。由于这种酶参与许多植物β-糖苷的转化，因此这种基因丢失的特殊情况可能受到进化过程中饮食适应的影响。在人类中，除了失活等位基因外，我们还发现 GBA3 积累了额外的有害突变，这意味着 GBA3 的广泛丢失。失活等位基因的等位基因分布在不同人群之间存在显著差异，这可能与他们的主食部分相关。对哺乳动物同源物的分析表明，GBA3 经历了至少九次假基因化事件。大多数假基因化事件发生在肉食性谱系中，表明与β-糖苷含量低的饮食有关。然而，GBA3 在杂食性和草食性物种中也丢失了，这表明 GBA3 的生理作用尚未完全了解，其他未知原因可能导致 GBA3 假基因化。这种可能性依赖于 GBA3 在唾液酸生物学中的潜在作用，其中 GBA3 参与涉及 NEU2 和 CMAH 的细胞网络。总体而言，我们的数据表明，GBA3 在哺乳动物中的反复丢失很可能代表由饮食相关因素引发的选择性约束放松的进化终点。
