Comments on: Lactase peristence & Cystic Fibrosis

By: pconroy

pconroy — Thu, 24 Jan 2008 15:06:21 +0000

Here's an interesting article on Lactase Persistance in Neolithic Sweden.

It states - on pages 43 and 44 of the PDF:

The allele associated with lactase persistence was found in 50% of the farmer samples and in 10% of the hunter-gatherer samples. The farming
samples did not differ from modern Swedes whereas the hunter-gatherers did. Further, the Neolithic samples were significantly different from modern
Norwegian and Saami samples when mitochondrial HVSI was compared. These results may, however, be influenced by five of the hunter-gatherer samples sharing a haplotype not found among any published modern populations.

Our data suggests that the frequency of the allele linked to lactase persistence in the investigated farmer population was, already 5,500 years ago,
closer to modern Swedish frequencies than to those seen in the contemporary hunter-gatherers. This may be caused by cultural induced selection in the
farmers. An alternative explanation that would not rely on an extreme cultural induced selection pressure, but with limited archaeological support
(Lidén in press), would be that only those with the genetic base for consuming unrefined milk became farmers while remaining people stayed huntergatherers.

It stated at the beginning of the PDF that farming came to Sweden approx 6,200 year ago.

By: David Boxenhorn

David Boxenhorn — Wed, 23 Jan 2008 21:37:44 +0000

Lactase persistence is so sophisticated that it has evolved repeatedly in pastoralist populations around the world. Four times in Africa! Are the authors unaware of Tishkoff et al. 2007?

And the CF mutation was the one that happened to pop up in Ireland in response to the new diet. What's hard to understand about that? Luck of the Irish.

By: gcochran

gcochran — Wed, 23 Jan 2008 21:15:41 +0000

You might want to calculate exactly how painfully slow it is. In the absence of heterozygote advantage, what should the frequency of this lethal recessive have been 1000 years ago, assuming that it is 2% today? 2000 years ago? Try this with and without reproductive compensation. I think you will be surprised.

By: Jason

Jason — Wed, 23 Jan 2008 20:41:37 +0000

"A reasonable answer is that CF alleles, being 'loss of function' alleles, were certainly present when the selective pressure due to the combined effect of lactose intolerance and dairy milk started, whereas lactose-tolerance, a sophisticated phenotypic modification (a single gene onthogenetically regulated in all mammals to express itself only during weaning had to be 'convinced' to continue to work through post-weaning life), was not so easily available or even absent in the exposed populations."

Lactase persistence is so sophisticated that it has evolved repeatedly in pastoralist populations around the world. Four times in Africa! Are the authors unaware of Tishkoff et al. 2007?

My bet is that there is no advantage to the CF allele and that the gene was brought to relatively high frequency by the demographic effects of population and geographic expansion into Europe in the wavefront/surfing process described by Excoffier et al (MBE 2005). Selection can be painfully slow removing deleterious recessives.

By: Jason

Jason — Wed, 23 Jan 2008 20:30:28 +0000

From the paper: “Therefore, these data conclusively disprove the ‘European-restricted’ high mutation rate hypothesis, thus proving, by exclusion, that the high CF gene frequency is due to a CF/+ heterozygous advantage.”

This is quite a leap! Heterozygote advantage is the only possible hypothesis left?! ….were the reviewers and editor asleep at the switch?

By: pconroy

pconroy — Wed, 23 Jan 2008 18:12:49 +0000

I’ve never been tested for CF, but have some of the symptoms, including very caustic sweat – enough to discolor pillows and shirt collars – along with many chronic lung infections.

I’m also lactose intolerant…

Sometimes when I read these articles I have to think that that’s the price the Irish pay for having so little Neolithic ancestry…

By: bbartlog

bbartlog — Wed, 23 Jan 2008 13:55:38 +0000

Makes you wonder just how high the frequency of the deleterious CF allele might have been in the past. Could heterozygote advantage have been enough to drive it above 10%? Could have been pretty high, I think, given that lactase persistence has been at very high frequency in N Europe for a thousand years or more – so what we see must be a fading echo.