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More Evidence that Small Differences in Genes Have Important Effects

Kral et al. have published an article titled A common variant in the CDKN2B gene on chromosome 9p21 protects against coronary artery disease in Americans of African ancestry in the Journal of Human Genetics. Their study reveals that a very small change in a gene protects against coronary artery disease (CAD) in African-Americans. The gene in question was already known to increase the risk of CAD in other races

According to Gene Alteration Protects from Artery Disease published in Drug Discovery & Development:

"What we think we have here is the first confirmed hereditary link to cardiovascular disease among African-Americans and it is a protective one," says senior study investigator and health epidemiologist Diane Becker, M.P.H., Sc.D. "This newly found link in African-Americans was not only protective instead of harmful but was also found at a precise location on gene CDKN2B, a gene close to the single base pair modification tied to other increased risk of coronary artery disease in other races."

Once again we see that small differences between complex systems, even complex systems of the same species, can result in dramatic differences between the systems. When the differences occur in different species we should expect even greater consequences.

A study by Barreiro et al. Functional Comparison of Innate Immune Signaling Pathways in Primates was published in PLoS Genetics The abstract reads as follows:

Humans respond differently than other primates to a large number of infections. Differences in susceptibility to infectious agents between humans and other primates are probably due to inter-species differences in immune response to infection. Consistent with that notion, genes involved in immunity-related processes are strongly enriched among recent targets of positive selection in primates, suggesting that immune responses evolve rapidly, yet providing only indirect evidence for possible inter-species functional differences. To directly compare immune responses among primates, we stimulated primary monocytes from humans, chimpanzees, and rhesus macaques with lipopolysaccharide (LPS) and studied the ensuing time-course regulatory responses. We find that, while the universal Toll-like receptor response is mostly conserved across primates, the regulatory response associated with viral infections is often lineage-specific, probably reflecting rapid host–virus mutual adaptation cycles. Additionally, human-specific immune responses are enriched for genes involved in apoptosis, as well as for genes associated with cancer and with susceptibility to infectious diseases or immune-related disorders. Finally, we find that chimpanzee-specific immune signaling pathways are enriched for HIV–interacting genes. Put together, our observations lend strong support to the notion that lineage-specific immune responses may help explain known inter-species differences in susceptibility to infectious diseases.

To paraphrase, all primates have an immune system and that immune system is generally the same in its overall contours. The differences come into play when one is examining the response to specific infectious diseases. In these cases, very small differences in genes result in marked differences in immune response. This explains, in part, why humans are more sensitive than chimpanzees to HIV and hepatitis B.

Intra- and inter-species differences can be explained, in part, by very small differences in genes. Combine this with the fact that animals are examples of complex systems and we have a theory that allows us to explain the decades of empirical evidence that reveals that species (and even individuals of the same species) respond differently to drugs and diseases.


Barreiro, L. B., Marioni, J. C., Blekhman, R., Stephens, M., & Gilad, Y. (2010). Functional Comparison of Innate Immune Signaling Pathways in Primates. PLoS Genet, 6, e1001249.

Kral, B. G., Mathias, R. A., Suktitipat, B., Ruczinski, I., Vaidya, D., Yanek, L. R., Quyyumi, A. A., Patel, R. S., Zafari, A. M., Vaccarino, V., Hauser, E. R., Kraus, W. E., Becker, L. C., & Becker, D. M. (2011). A common variant in the CDKN2B gene on chromosome 9p21 protects against coronary artery disease in Americans of African ancestry. J Hum Genet.


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