Poor tzi's doomed mitochondria

I must have seen a dozen stories today that started this way:


"Otzi," Italy's prehistoric iceman, probably does not have any modern day descendants, according to a study published Thursday.

Washington Post:

Sparking a new mystery about early man, Italian scientists have unraveled the DNA of the 5,300-year-old "Iceman" mummy, only to discover that he doesn't appear to have modern descendants anywhere near where he was found in Europe.

I didn't really think about how funny that line is, until I was talking to someone about it this evening -- there's no way that the mtDNA can be informative about tzi's descendants, because, well, it's maternally inherited. D'oh!

Meanwhile, we can ask what it means that a randomly picked Neolithic man would have a now-extinct mtDNA lineage. According to ScienceNews, Antonio Torroni thinks that it is a case of marker loss:

Its possible but unlikely that tzi belonged to a fourth branch of K1 that is now extinct or rare, Torroni says. He considers it more probable that a random mutation in the Icemans mitochondrial DNA erased the only genetic marker currently used to identify members of the most common K1 branch.

Could be.

Whether the sequence was a unique branch of K or a slight variation on a well-represented subtype, there's a natural hypothesis for why it no longer exists, that somehow is mentioned in none of the reports. The Iceman is hardly singular: Remember that the mtDNA pool of Central Europe in the Neolithic was dominated by lineages that are now rare. And Medieval Danes had several mtDNA sequences that are now rare or absent in Scandinavia. And the Cambridge sequence has been increasing in frequency in Britain since medieval times. And so on.

There's no mystery here. These are large populations, and mtDNA haplogroups have been changing in frequencies between ancient DNA samples and the present. MtDNA has functions that plausibly were subject to changing environments after the Neolithic. This seems like a good candidate for recent selection.

UPDATE (2008-10-31): A reader writes:

Hi John,
You raised the hypothesis that recent selection might explain the apparent dearth of modern examples of his haplotype, with private mutations at 3513T and 8137T. Those mutations are synonymous, which would seem to rule that out, leaving drift as the better alternative.

That's a good point, and one often raised as a criticism of the selection hypothesis. If a sequence differs from some extant (still-existing) variant by only synonymous mutations, then selection can't explain why one is gone and one is still here. Only genetic drift can explain the extinction of one and the survival of the other.

But this is not the entire story. In this instance, we have synonymy with one major haplogroup (K) which has coding differences from other haplogroups. Those haplogroups have been changing in relative frequencies in Europe over the last few thousand years. A decrease in the frequency of K would naturally cause rare K variants to become rarer or extinct, even though they are neutral with respect to each other. In this instance, lineage extinction would be the result of selection, even though the extinct lineages have no disadvantage relative to some that still survive.

Now, is that the case with tzi's haplotype? I would say it's a good hypothesis, but not yet testable. We really would like to know the frequency of the haplogroup in the Neolithic. For that matter, further ancient DNA sampling will test many hypotheses of genetic drift and selection, because direct observation of ancient frequencies gives us a source of information that does not depend on sampling models from living populations.