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There is a molecular basis for many sleep patterns and disorders involving circadian clock genes. In humans, “short-sleeper” behavior has been linked to specific amino acid substitutions in  BHLHE41  (DEC2), yet little is known about variation at these sites and across this gene in mammals. We compare  BHLHE41  coding sequences for 27 mammals. Approximately half of the coding sequence was invariable at the nucleotide level and close to three-quarters of the amino acid alignment was identical. No other mammals had the same “short-sleeper” amino acid substitutions previously described from humans. Phylogenetic analyses based on the nucleotides of the coding sequence alignment are consistent with established mammalian relationships confirming orthology among the sampled sequences. Significant purifying selection was detected in about two-thirds of the variable codons and no codons exhibited significant signs of positive selection. Unexpectedly, the gorilla  BHLHE41  sequence has a 318 bp insertion at the 5’ end of the coding sequence and a deletion of 195 bp near the 3’ end of the coding sequence (including the two short sleeper variable sites). Given the strong signal of purifying selection across this gene, phylogenetic congruence with expected relationships and generally conserved function among mammals investigated thus far, we suggest the indels predicted in the gorilla  BHLHE41  may represent an annotation error and warrant experimental validation.

plos one

Unexpected predicted length variation for the coding sequence of the sleep related gene, BHLHE41 in gorilla amidst strong purifying selection across mammals