Genes related to physical activity are older than modern humans

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Our results estimate PA-related SNPs in protein-coding genomic areas are as old or older than the hypothesized emergence of anatomically modern humans (~200–350 kya). This estimated SNP age range is considerably older than the majority of exon-located mutations given that Fu et al. predicted 73.2% of modern day exonal SNPs arose less than 5 kya. A mutation age range from 210 to 785 kya suggests the genetic control of PA in humans, through these particular exon-located SNPs, may have emerged during periods of Homo energy expenditure alterations such as the dramatic increase in Homo’s brain size, body size, and/or gathering range. A proposed timeline equating the emergence of PA associated mutations with possible selection pressures is in Fig 2. Given the evolutionary divergence of humans and primates has been approximated to be 4–12 mya, our species may not share the exact intragenic-based modulators of PA present in primates. Further, while many PA genetic studies are completed in mice models, the evolutionary split between humans and mice is estimated to have occurred approximately 96 mya similarly suggesting intragenic-based modulators controlling activity in humans may not be similar to those controlling activity in mice. However, we urge caution in interpreting our limited dataset to mean there are no similarities among human PA genetic regulation and PA regulation in other species given that the direct causal link between the available SNPs and PA is yet to be determined.

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