CASP12 (caspase-12 gene/pseudogene)

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True   Likely   Speculative
Human Uniqueness Compared to "Great Apes": 
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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

Genetics Topic Attributes
Gene symbols follow the HUGO Gene Nomenclature Committee standard.
Gene Symbol Type of Human-Specific Changes
CASP12 Accelerated Evolution, Pseudogenization

References

  1. Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice., Saleh, Maya, Mathison John C., Wolinski Melissa K., Bensinger Steve J., Fitzgerald Patrick, Droin Nathalie, Ulevitch Richard J., Green Douglas R., and Nicholson Donald W. , Nature, 2006 Apr 20, Volume 440, Issue 7087, p.1064-8, (2006)
  2. Gene losses during human origins., Wang, Xiaoxia, Grus Wendy E., and Zhang Jianzhi , PLoS Biol, 2006 Mar, Volume 4, Issue 3, p.e52, (2006)
  3. Spread of an inactive form of caspase-12 in humans is due to recent positive selection., Xue, Yali, Daly Allan, Yngvadottir Bryndis, Liu Mengning, Coop Graham, Kim Yuseob, Sabeti Pardis, Chen Yuan, Stalker Jim, Huckle Elizabeth, et al. , Am J Hum Genet, 2006 Apr, Volume 78, Issue 4, p.659-70, (2006)
  4. Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms., Saleh, Maya, Vaillancourt John P., Graham Rona K., Huyck Matthew, Srinivasula Srinivasa M., Alnemri Emad S., Steinberg Martin H., Nolan Vikki, Baldwin Clinton T., Hotchkiss Richard S., et al. , Nature, 2004 May 6, Volume 429, Issue 6987, p.75-9, (2004)