Signatures of Relaxed Selection in the CYP8B1 Gene of Birds and Mammals
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.
KeywordsFrame-shift Comparative genomics Diet change CYP8B1 Relaxed selection
NV would like to acknowledge funding from IISER Bhopal under Grant # INST/BIO/2017/019. We thank Council of Scientific & Industrial Research for fellowship to SSS, Ministry of Human Resource Development for fellowships to LT and SS. NV has been awarded the Innovative Young Biotechnologist Award 2018 from the Department of Biotechnology and Early Career Research Award from the Department of Science and Technology (both Government of India).
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