CASP12 gene

Functional CASP12 gene variation between chimpanzees & humans

    Caspases are a family of cysteine-rich proteases that cleave C-terminal aspartic acid residues in target proteins. Caspase-12 is encoded by the CASP12 locus. Comparison among Great Apes shows a functional 1689 nuc gene in chimps (Pan), but a pre-mature termination mutation at nucleotide position 373 in most humans (Homo), where CGA TGA. [Note the 1s- and 2nd-position substitution mutations in the other two boxes]. Loss of Caspase-12 function is implicated in Alzheimer Disease. In some African populations, a functional, "read-through" allele is associated with reduced immunological response to endotoxins, which can result in severe sepsis.

    One hypothesis is that the loss-of-function mutation in CASP12 confers a short-term selective advantage in humans by improving the immunological response, balanced against a longer-term disadvantage from susceptibility to Alzeheimer's, which occurs in longer-lived humans but not shorter-lived Apes.

Figure & text ©2014 by Steven M. Carr