Cryptic Variation and Ice Man

This fortnight’s Current Biology has some interesting articles, two of which caught my attention. First is a “Quick Guide” to cryptic variation, which is genetic variation that goes unnoticed under most circumstances. Also published is the mtDNA sequence of the 5,000 year old Tyrolean Ice Man (a.k.a. Ötzi; this paper actually came out right before Halloween, so I suppose I was too excited about the holiday to write about it then).

First, “cryptic variation.” The authors describe cryptic variation as, “unexpressed, bottled-up genetic potential. … expressed under abnormal conditions such as in a new environment or a different genetic background” (Gibson and Reed 2008). Sounds impossible, because one quickly asks, how can we study ‘cryptic variation’ if it refers to something that is phenotypically unexpressed? But it has been documented in plants and Drosophila, the work-horse-fly of biology. As an example, the authors cite the condition of Antennapedia in Drosophila, in which a mutation causing legs to grow in place of flies’ antennae. When placed into the genomes of different species of Drosophila, this mutation produces different phenotypes. This indicates that variation can be affected by interactions among genes, a phenomenon known as epistasis.

A related phenomenon is ‘canalization,’ which is the evolution of phenotypic ‘buffering’ that prevents variation from arising during development. [For a good synthesis of the concept of canalization, evidence for it, and an application in anthropology, check out Hallgrimsson et al.’s Yearbook paper (Hallgrímsson et al. 2002)] Basically, it seems that enough stabilizing selection can ensure that an individual’s phenotype will develop to a given form in spite of various environmental or internal stresses (i.e. climate and the external environment, or the genetic environment of an organism). This suppression of phenotypic variation can allow ‘cryptic’ genetic variation to accumulate, to be suddenly expressed in a future generation because of certain circumstances. The authors point out that this is possibly problematic because this is not how genes are supposed to work, as far as we know. I think this is an interesting, and potentially very important, avenue of paleoanthropological research, specifically regarding the possibility of hybridization. I’ve written elsewhere, as have others, about the possibility and implications of hybridization on human evolution. Could hybridizing hominin lineages have ‘released’ some type of cryptic variation? An interesting idea, but as always it’s fairly pointless unless it can be tested. And at the moment I cannot think of a way, but I’ll work on it…

In the mean time, researchers have sequenced the mtDNA of the Tyrolean Ice Man. This poor chap, unfortunately for him but fortunately for science, died and ended up in a glacier between Italy and Austria that preserved his soft-tissue very well, some 5000 years ago. What did the study find? Turns out Ice Man’s mtDNA is part of haplogroup K, but has two specific mutations that make his unlike any living mtDNA haplogroup. I seem to remember reading recently about another ancient mtDNA sequence that is unlike anything modern known in modern humans… Oh yes, the 38 ky old Neandertal from Vindija (Green et al. 2008)! If a 5,000 year-old Italian could have belonged to an extinct mtDNA lineage, what does this mean for a similarly ‘extinct’ 38ky old Neandertal? Not a whole lot, but it does underscore how easily mitochondrial lineages can be lost, and it cautions against using the single Neandertal’s mtDNA to argue against their contribution to the modern Homo sapiens gene pool.

Additionally it highlights some of the limitations of genetic studies. Genetic studies like this are limited to the current database of sequences. Ötzi was compared to a sample of some 2000 individuals’ genomes. But there’s always a chance that Ötzi’s ‘extinct’ mitochondrial haplogroup is present but has not yet been sampled. This reminds me of a recent Q&A in Nature entitled, “The pitfalls of tracing your ancestry.” Here, Charmaine Royal of Duke University described issues that arise when people try to trace their ancestry with genetic testing. Here’s what Royal said that has bearing on Otzi, and other ancient genomes:

“The general limitation, I’d say, of all of these tests, is that they can’t pinpoint with 100% accuracy who your ancestors may or may not be. Some people are concerned that the biogeographical ancestry test reifies the notion of race. This is the notion that there are four or five parental groups from which we all came and there are discrete boundaries between these groups. But our genetic research has shown that those boundaries don’t exist.

In lineage testing, where someone is wanting to know which tribe or region in Africa they came from, the information that’s given is based on the present day populations. The names of those groups and those locations have changed over time and so people getting that information about present day Africans and extrapolating to who their pre-middle-passage ancestors may have been — that may not necessarily be accurate. So, those limitations need to be clarified.

Another limitation is that the outcomes of ancestry tests are very much dependent on what is already in a database — who a client’s DNA can be matched to. If a database is not comprehensive some potential matches will be missing, and nobody has a complete database. That’s a major limitation, probably one of the biggest.”

Royal also discusses some interesting issues of when genome testing goes wrong—that is, when people’s genetic results about their identity don’t conform to what they’d expected, how they identify themselves. The piece does a good job illustrating the complex nature of cultural identity and genetic affinity. In the same vein, paternity testing creates the same issues: how one’s social identity/reality can be ripped asunder by a genetic test. So, while genetics and genomics are incredibly valuable scientific avenues, it’s always fun to point out their limitations and adverse effects. Anyway, paleogenomics and cryptic variation are interesting topics that will hopefully continue to be developed and incorporated into Anthropology in the coming years.

Gibson G, and Reed LK. 2008. Cryptic genetic variation. Current Biology 18(21):R989-R990.
Green RE, Malaspinas A-S, Krause J, Briggs AW, Johnson PLF, Uhler C, Meyer M, Good JM, Maricic T, Stenzel U and others. 2008. A Complete Neandertal Mitochondrial Genome Sequence Determined by High-Throughput Sequencing. Cell 134(3):416-426.
Hallgrímsson B, Willmore K, and Hall BK. 2002. Canalization, developmental stability, and morphological integration in primate limbs. American Journal of Physical Anthropology 119(S35):131-158.