Abstract
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.
Highlights
Sleep plays a vital function for survival in animals [1,2,3], especially vertebrates and even some invertebrates [4]
From the results of the BLAST search using BHLHE41 from H. sapiens, we downloaded mammalian sequences and one reptile sequence as an outgroup for a total alignment of species.The E-values for all sequences were 0.0 and the local identity scores from the BLAST report ranged from 87.50% to 100% (Table 1)
At least two nonsynonymous substitutions found in humans (P385R and Y362H) are not lethal and confer altered sleep patterns that may even be adaptive under certain circumstances [10,17]
Summary
Sleep plays a vital function for survival in animals [1,2,3], especially vertebrates and even some invertebrates [4]. It is essential in maintaining both physical and mental health, especially in humans where sleep deprivation is linked to diabetes, high blood pressure, obesity, and decreased immune function [5,6,7]. The timing and duration of sleep varies widely among mammals [8] and is regulated by a plethora of intricate mechanisms including many circadian clock genes [9]. Among the genes responsible for circadian regulation in mammals is the basic helix-loophelix family member e41 [5, 10, 11], known as “differentially expressed in chondrocytes
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