Your ancestry inference is precise and accurate(ish)

Your ancestry inference is precise and accurate(ish)

For about three years I consulted for Family Tree DNA. It was a great experience, and I met a lot of cool people through that connection. But perhaps the most interesting aspect was the fact that I can understand the various pressures that direct-to-consumer genomics firms face from the demand side. The science is one thing, but when you are working on a consumer facing product, other variables come into play which are you not cognizant of when you are thinking of it from a point of pure analysis. I’m pretty sure that my insights working with Family Tree DNA can generalize to the other firms as well (23andMe, Ancestry, and Genographic*).

The science behind the ancestry inference elements of the product on offer is not particularly controversial or complex, but the customer aspect of how these results are received can become an intractable nightmare. The basic theory was outlined in the year 2000 in Pritchard et al.’s Inference of Population Structure Using Multilocus Genotype Data. You have lots of data thanks to better genomic technology (e.g., 300,000 SNPs). You have computers to analyze that data. And, you have scientific models of population history and dynamics which you can test that data against. The shape of the data will determine the parameters of the model, and it this those parameters that yield “your ancestry.”

In broad sketches the results make sense for most people. It’s in the finer details that the confusions emerge. To the left you see my son’s 23andMe ancestry deconvolution. The color coding is such you can tell that his maternal and paternal chromosomes have very different ancestry profiles (mostly Northern European and South Asian, respectively).

But his “Northern European” chromosomes also are more richly colored, with alternative segments denoting ancestry from different parts of Northern Europe. So in terms of proportions I am told my son is about 15 percent French and German, and 10 percent Scandinavian and 10 percent British and Irish. This is reasonable. On the other side he’s nearly 50 percent “broadly South Asian.” The balance is accounted for by my East Asian ancestry, which is correct, as my South Asian ethnicity is from Bengal, where there is a fair amount of East Asian ancestry (my family’s origin is on the eastern edge of Bengal itself).

And it is here that the non-scientific concerns of consumer genomics comes into focus. The genetic differences and distance between various South Asian groups are far higher than those between various Northern European groups. Depending on the statistic measure you use intra-South Asian variation is about one order of magnitude greater than intra-Northern European differences. This is due to geographic partitioning, the caste system, and differential admixture in South Asians between extreme diverged ancestral elements (about half of South Asian ancestry is very similar to Europeans and Middle Easterners, and half of it is extremely different, so how far you are from the 50 percent mark determines a lot).

Broadly South Asian

In Northern Europe there is very little genetic variation from the British Isles all the way the Baltic. The reason for this is historical: massive population turnover in the region 4,500 years ago means that much of the genetic divergence between the groups dates to the Bronze Age. It is this the genetic divergence, the variation, that is the raw material for the inferences and proportions you see in ancestry calculators. There’s just not that much raw material for Northern Europeans.

Broadly South Asian

Remember, the methods require lots of variation in the data as a raw input. You’re making the inference machine work real hard to produce a reasonable robust result if you don’t have that much variation. In contrast to the situation with Northern Europeans, with South Asians the companies are leaving raw material on the table, and just combining diverse groups together.

What’s going on here? As you might have guessed this is an economically motivated decision. Most South Asians know their general heritage due to caste and regional origins (though many Bengalis exhibit some lacunae about their East Asian ancestry). In contrast, many Americans of Northern European ancestry with an interest in genealogy are extremely curious about explicit proportional breakdowns between Northern European nationalities. The direct-to-consumer genomic firms attempt to cater to this demand as best as they can.

As I have stated many times, racial background is to various extents both biological and social. When it comes to the difference between Lithuanians and Nigerians the biological differences due to evolutionary history are straightforward, and clear and distinct. You can generate a phylogenetic history and perform a functional analysis of the differences. Additionally, you also have to note that the social differences exist, but are not straightforward. Like Lithuanians Nigerians of Igbo background are generally Roman Catholic, while most other Nigerians are not. The linguistic differences between Nigerian languages are great enough that it is defensible to suggest that Hausa speakers of Afro-Asiatic dialects are closer to Lithuanians in their phylogenetic history than to the dialects of the Yoruba.

A Lithuanian American

Contrast this to the situation where you differentiate Lithuanians from French. To any European the differences here are incredibly huge. The history of France, what was Roman Gaul, goes back 2,000 years. After the collapse of the West Roman Empire by any measure the people who became French were at the center of European history. In contrast, Lithuanians were a marginal tribe, who did not enter Christian civilization until the late 14th century. In social-cultural terms, due to history, the differences between French and Lithuanians are extremely salient to people of French and Lithuanian ancestry. But genetically the differences are modest at best.

If a direct-to-consumer genetic testing company tells you that you are 90 percent Northern European and 10 percent West African, that is a robust result that has a clear historical genetic interpretation. The two element’s of one’s ancestry have been relatively distinct for on the order of 100,000 years, with the Northern European element really just a proxy for non-Africans (though it is easy to drill-down within Eurasia). In contrast, notice how 23andMe, with some of the best scientists in the business, tells people they are “French-German,” and not French or German. What the hell is a “French-German”? Someone from Alsace-Lorraine? A German descendent of Huguenots? Obviously not.

“French-German” is a cluster almost certainly because there are no clear and distinct genetic differences between French and Germans. Yes, there is a continuum of allele frequencies between these two groups, but having looked at a fair number of people of French and German background in Family Tree DNA’s database I can tell you that France and Germany have a lot of local structure even among people of indigenous ancestry. Germans from the Rhineland are quite often genetically closer to French from Normandy than they are to Germans from eastern Saxony. Some of this is due to gene flow between neighboring regions, but some of this is due to cultural fluidity as to who exactly is German. It is clear that some Germans from the eastern regions are Germanized Slavs. Some Germans from the north exhibit strong affinities to Scandinavians, while Germans from Bavaria and Austria are classically Central European (whatever that means). The average German is distinct from the average French person, but the genetic clustering of the two groups is not clear and distinct.

Remember earlier I explained that the science is predicated on aligning data and models. The cultural model of Northern Europeans is conditioned on diversity and difference which has been very salient for the past few thousand years since the rise and fall of Rome. But the evolutionary genetic history is one where there are far fewer differences. The data do not fit a model that makes much sense to the average consumer (e.g., “you descend from a mix of Bronze Age migrants from the west-central steppe of Eurasia and Mesolithic indigenous hunter-gatherers and Neolithic farmers”). What makes sense to the average American consumer are histories of nationalities, so direct-to-consumer genetic companies try to satisfy this need. Because the needs of the consumer and their cultural expectations are poorly served by the data (genetic variation) and models of population history, you have a lot of awkward kludges and strange results.

Imagine, for example, you want to estimate how “German” someone is.  What do you use for your reference population of Germans?  Looking at the data there are clearly three major clusters within Germany when you weight the numbers appropriate, with affinities to the northern French, Slavs, and Scandinavians, and various proportions in between. Your selection of your sample is going to mean that some Germans are going to be more Germans than other Germans. If you select an eastern German sample then western Germans whose ancestors have been speaking a Germanic language far longer than eastern Germans are going to come out as less German. Or, you could just pick all of these disparate groups…in which case, lots of Northern Europeans become “German.”

Consumers want genetic tests to reflect strong cultural memories which were forged in the fires of rapidly protean and distinction-making process of cultural evolution. But biological and cultural evolution exhibit different modes (the latter generates huge between group differences) and tempos (those differences emerge fast). The ancestry results many people get are the outcomes of compromises to thread the needle and square the circle.

All the above is half the story. Next I’ll explain why “deep history” has to be massaged to make recent history informative and comprehensible….

* Also, I have a little historical perspective because of my friendship with the person who arguably created this sector, Spencer Wells.

Razib Khan