Abstract
The CYP8B1 gene is known to catalyse reactions that determine the ratio of primary bile salts and the loss of this gene has recently been linked to lack of cholic acid in the bile of naked-mole rats, elephants and manatees using forward genomics approaches. We screened the CYP8B1 gene sequence of more than 200 species and test for relaxation of selection along each terminal branch. The need for retaining a functional copy of the CYP8B1 gene is established by the presence of a conserved open reading frame across most species screened in this study. Interestingly, the dietary switch from bovid to cetacean species is accompanied by an exceptional ten amino acid extension at the C-terminal end through a single base frame-shift deletion. We also verify that the coding frame disrupting mutations previously reported in the elephant are correct, are shared by extinct Elephantimorpha species and coincide with the dietary switch to herbivory. Relaxation of selection in the CYP8B1 gene of the wombat (Vombatus ursinus) also corresponds to drastic change in diet. In summary, our forward genomics-based screen of bird and mammal species identifies recurrent changes in the selection landscape of the CYP8B1 gene concomitant with a change in dietary lipid content.
Highlights
The increasing number of genomes that are being sequenced across the tree of life has allowed for large-scale comparative genomic analysis
Intense signatures of relaxed selection have generally been found in genes that have acquired reading frame disrupting changes and are considered as further evidence supporting gene loss (Sharma and Hiller 2018)
We have performed manual curation of the CYP8B1 gene to correct genome assembly and annotation artefacts in numerous species. These curated open reading frames are used to test for signatures of relaxed selection in more than 200 species
Summary
The increasing number of genomes that are being sequenced across the tree of life has allowed for large-scale comparative genomic analysis. Changes in dietary patterns have been linked to changes in digestive enzyme gene content (Wang et al 2016; Chen and Zhao 2019; Rinker et al.2019). These comparative approaches have immense promise in understanding the evolutionary origin of novelty. Utility of finding TRGs is best demonstrated by forward genomics approaches that have used phenotype presence/absence matrices to perform association studies that link gene loss events to specific traits in vertebrates (Sharma et al.2018). Identification of subtle taxon-specific changes at the regulatory level continues to be challenging
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