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 with other Great Apes shows
a functional 1689 base gene in chimps (Pan),
but a premature termination mutation at
nucleotide position 373 in most humans (Homo),
where CGA 
TGA. [Note the
1st- 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 in food, which can result in severe sepsis.
One hypothesis is that the loss-of-function mutation in human CASP12 confers a short-term selective advantage by improving the immunological response, balanced against a longer-term disadvantage from susceptibility to Alzheimer disease, which occurs in longer-lived humans but not shorter-lived Apes.
TGA. [Note the
1st- 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 in food, which can result in severe sepsis. One hypothesis is that the loss-of-function mutation in human CASP12 confers a short-term selective advantage by improving the immunological response, balanced against a longer-term disadvantage from susceptibility to Alzheimer disease, which occurs in longer-lived humans but not shorter-lived Apes.
Figure & text ©2024 by Steven
M. Carr