Monday, January 17, 2005

Live long and prosper

Today's New York Times has an interesting article about a genomic region that seems to be associated with longevity and fertility, at least among European peoples. (The Times says it should appear in Nature Genetics today, but I don't see it in the January issue). The region of interest is a fairly big (900,000 basepairs, out of 100 million basepairs in an average chromosome)chunk of DNA on Chromosone 17 which has been "inverted," or connected in reverse orientation, in about 20% of Europeans. Icelandic women carrying the inversion tend to have more kids than those for whom both copies of this stretch are in normal orientation. Moreover, the inversion is also present much more frequently in very old (90-95 years old) Icelanders.

To say more, I will need to see the original article, and I will describe why a bit below. But first, why Icelanders? The company which published this study, DeCode, is bio-prospecting for human genes which might contribute to diseases. The idea (NatGen, subscription link) is that Icelanders are unusually genetically homogeneous. They have lived isolated from other populations for a very long time, and in addition passed through two "bottlenecks," or catastrophic eras (including the Black Death), when very few Icelanders were left to repopulate the island. (See this history of Iceland.)What this genetic homogeneity does is reduce the prevalence of small genetic differences, especially in families, which are seen in more heterogeneous populations. This means that if a genetic disease runs in a given Icelandic family, researchers don't have to sort through such a long pile of differences (of which most will be unrelated to the disease) between family members who do and don't have the disorder. Moreover, Iceland, like other Scandinavian nations, keeps extremely detailed medical databases of all its nationals, stretching back for years and years. This is also a help for gene prospectors to locate new instances of a disease.

Ok, so Icelanders, as a nation, have very similar genomes, and 20% of them share with Europeans an inversion on chromosome 17. Those lucky 20% are overrepresented among very old people and among people with big families. So far, so good. But I would like to see the original article to judge the demographic association of the polymorphism with family size, and the connection between family size and fertility. Europeans generally do not breed to their physical limits, so this connection sounds a bit sketchy as presented. I also, without more information, have trouble with a second claim in the Times, that this inversion has been isolated from its normal cognate for 3 million years. The scientists likely used a molecular clock method (a way of comparing related sequences to see how long ago they diverged), that I would need to see, in order to arrive at this figure. This date seems improbably old, as it predates the emergence of the Hominid lineage (see Wiki on hominid evolution). A beneficial mutation, if present from very ancient times (and if relevant for natural selection) should be seen in humans all over the world, but this inversion is not. The Times offers an alternate explanation, that there has been genetic interchange between the Homo Sapiens group fated to populate Europe and non-human cousins (possibly Homo Erectus- see Carl Zimmer at the Loom for the story-behind-the-story of lice ). But let's be clear here. To pick up a stretch of DNA that divergent, some ancestor of Europeans (i.e. a pretty recent homo sapiens) had to be having sex with chimps.

My guess is that their molecular clock is wrong, possibly because the inversion accumulates mutations faster than expected, and that this genetic novelty came into the picture much more recently. UPDATE: The deCODE site (see below) says that actually the inversion has been subject to low internal mutation.

All in all, I can't argue with the demographics-- in fact, I'm inclined to believe them-- but I see some red flags in the biology. Please, anybody comment who's interested!

UPDATE:deCODE has a different article in the December Nature Genetics. This looks fantastic!
The deCODE web page says the inversion story will appear in the February issue.

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