Cystic fibrosis and lactase persistence: a possible correlation (FREE)
Guido Modiano, Bianca M Ciminelli and Pier F Pignatti
Eur J Hum Genet advance online publication, December 20, 2006
Apparently, it has long been assumed that there was a heterozygote advantage that maintained the lethal recessive CFTR allele. Here, the authors propose that this advantage consisted of "a resistance to lactose-caused diarrhea in populations that adopted such a habit while they were still lactose intolerant."
First they argue that the high CF allele frequency in Europe (.02) compared to Africa (.01) and Far East Asia (.002) is better explained by a '' 'Europe-restricted' heterozygous advantage" than by a 'Europe-restricted' high mutation rate". (Are these really the only two possible hypotheses?).
As for what theis heterozygote advantage might consist of: "the CFTR protein is the Cl- ion channel responsible for the displacement of ... water from the mucosa epithelial cells into the respiratory and intestinal lumen."
Their time course of events:
- Initially all humans were lactose intolerant and the cumulative CF gene frequency was maintained at a value of about 0.002 by a + CF4 10-6 (as in Japan).
- 5000–10 000 years ago cattle-breeding and dairy milk post-weaning diet started,19, 20 resulting in a stringent selective pressure.
- The onset of an 'emergency' adaptive response consisting of an immediate expansion of the already available CF alleles (the antiquity of the F508del allele has been estimated to be 52,000 years21). They would have attained and maintained a frequency unknown, but possibly higher than the present one, resulting from a balance between the advantage of being more resistant to the adverse consequences of being unable to digest lactose (hence to benefit from an important food as the milk) and a heavy segregational load.
- The onset of the not costly lactase-persistence adaptation, which attained rapidly a very high frequency (up to fixation in some European areas).14, 15
- A progressive decrease of the CF gene frequency down to the present (still high) values, which can be considered a relic of the past 'emergency' adaptation.