Caspase-12

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Caspases are cysteine protease enzymes that cut C-terminal aspartic acid residues on their substrate molecules. Among these Caspase-12 (encoded by the CASP12 gene) is part of a sub-group that process inflammatory cytokines. In rodents, it is known that this protein mediates cell death (apoptosis) in response to stress. In most humans CASP12 appears to be nonfunctional, because of a truncating mutation. However some African populations have the intact gene, which can confer altered reactivity upon exposure to bacterial products. Thus, the status of CASP12 may constitute a risk factor for developing sepsis (an overwhelming response to bacterial infections). Population studies have suggested strong evidence of positive selection for the inactive form of the gene, which has driven it to near fixation in humans. It is suggested that there was a selective advantage of sepsis resistance in populations that experienced more bacterial infections as population sizes and densities increased

References:

Saleh, M.; Mathison, J. C.; Wolinski, M. K.; Bensinger, S. J.; Fitzgerald, P.; Droin, N.; Ulevitch, R. J.; Green D. R.; Nicholson, D. W. :Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice. Nature 440: 1064-1068, 2006.
PubMed ID : 16625199

Saleh, M.; Vaillancourt, J. P.; Graham, R. K.; Huyck, M.; Srinivasula, S. M.; Alnemri, E. S.; Steinberg, M. H.; Nolan, V.; Baldwin, C. T.; Hotchkiss, R. S.; Buchman, T. G.; Zehnbauer, B. A.; Hayden, M. R.; Farrer, L. A.; Roy, S.; Nicholson, D. W. :
Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms. Nature 429: 75-79, 2004.
PubMed ID : 15129283

Xue, Y.; Daly, A.; Yngvadottir, B.; Liu, M.; Coop, G.; Kim, Y.; Sabeti, P.; Chen, Y.; Stalker, J.; Huckle, E.; Burton, J.; Leonard, S.; Rogers, J.; Tyler-Smith, C. :Spread of an inactive form of caspase-12 in humans is due to recent positive selection. Am. J. Hum. Genet. 78: 659-670, 2006. PubMed ID : 16532395

Wang X, Grus WE, Zhang J. Gene losses during human origins. PLoS Biol. 2006 Mar;4(3):e52. PMID: 16464126

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