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It’s raining founder events

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There’s a new preprint on bioRxiv that is very interesting, Reconstructing the history of founder events using genome-wide patterns of allele sharing across individuals:

…To learn about the frequency and evolutionary history of founder events, we introduce ASCEND (Allele Sharing Correlation for the Estimation of Non-equilibrium Demography), a flexible two-locus method to infer the age and strength of founder events. This method uses the correlation in allele sharing across the genome between pairs of individuals to recover signatures of past bottlenecks. By performing coalescent simulations, we show that ASCEND can reliably estimate the parameters of founder events under a range of demographic scenarios, with genotype or sequence data. We apply ASCEND to ~5,000 worldwide human samples (~3,500 present-day and ~1,500 ancient individuals), and ~1,000 domesticated dog samples. In both species, we find pervasive evidence of founder events in the recent past. In humans, over half of the populations surveyed in our study had evidence for a founder events in the past 10,000 years, associated with geographic isolation, modes of sustenance, and historical invasions and epidemics. We document that island populations have historically maintained lower population sizes than continental groups, ancient hunter-gatherers had stronger founder events than Neolithic Farmers or Steppe Pastoralists, and periods of epidemics such as smallpox were accompanied by major population crashes. Many present-day groups–including Central & South Americans, Oceanians and South Asians–have experienced founder events stronger than estimated in Ashkenazi Jews who have high rates of recessive diseases due to their history of founder events. In dogs, we uncovered extreme founder events in most groups, more than ten times stronger than the median strength of founder events in humans. These founder events occurred during the last 25 generations and are likely related to the establishment of dog breeds during Victorian times. Our results highlight a widespread history of founder events in humans and dogs, and provide insights about the demographic and cultural processes underlying these events.

This method is pretty cool because it scales and works on non-phased data (good luck phasing a lot of low coverage of ancient DNA!). Through simulation and comparison to earlier results, the authors show that ASCEND does a good job estimating

1) the timing of a founder event

2) the intensity of a founding event

One of my hobby-horses is that Ashkenazi Jews aren’t really that inbred or bottlenecked a group. They’ve been extensively studied, so there’s a laser-like focus on their population and medical genetics. Importantly, they also have a recessive disease load, usually attributed to their endogamy and small effective population size. Studying Ashkenazi Jewish genetics is easy if you think of it in grant terms since there are diseases that are well known you can focus on.

But one of the results in this preprint, which aligns with other earlier published work, is that there are many groups far more homogeneous due to extreme founder events/endogamy than Ashkenazi Jews. Some of the outcomes are not surprising. Lots of South Asian groups seem to be extremely homogeneous due to endogamy and small founding populations, though today many of them number in the millions. The strong implication from these results is that they carry a lot of deleterious recessive allele load.

The other groups are not surprising. Islanders, hunter-gatherers in marginal habits. Basically, populations artificially prevented from gene flow, or, those subject to strong cultural barriers.

The method not only estimates the intensity of the founder events but also the period. Many of the results are totally explicable. Many Northern Europeans seem to have founding populations that go back to the Corded Ware expansion. The founding of the Basque dates to the Roman Empire. Why? I think a reasonable hypothesis that for whatever reason this is when the ancient Aquitani emerged as an exclusive ethnocultural group, as opposed to Romanizing like their Iberian and Celtiberian neighbors.

Probably the most interesting result for me is one that is obvious in much of the data, but hasn’t been analyzed as thoroughly before: ancient European hunter-gatherers had very small effective populations due to narrow founder events. The question is: is this true in general for pre-agricultural people? Many anthropologists have argued that large agglomerations of sedentary populations were more common before the Holocene than we might think, and modern hunter-gatherers are biased samples (they occupy marginal territory).

As we obtain more ancient DNA that question will be answered in the generality. Over ten years ago Hawks et al. argued that large populations resulted in faster adaptation. Whatever details one might quibble within their model, I think the results from ancient DNA raise the possibility of the greater relative efficacy of selection (due to weaker drift) and more population connectedness allowing for easier flow of beneficial alleles.

The software is already available. I’m going to take it for a test drive…

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11 thoughts on “It’s raining founder events

  1. Greg Cochran has long argued that the high frequency of recessive diseases among the Ashkenazi is not due to a “bottleneck” but instead selection. A number of them supposedly affect the same metabolic pathway, which would seem like quite a coincidence.

  2. Had a look at this paper yesterday and had a question but wasn’t sure if it was dumb, so thought worth trying out here rather than going direct to authors.

    One signature of a founder effect in a group is an increase in Fst with an outgroup, compared with a population to which they form a clade. For instance in Ashkenazi Jews relative to populations from Sicily (who are close to forming a clade), or Irish Travellers relative to settled Irish, this effect can be observed. Just from reduction in within group diversity. Like a slight but across the board increase.

    So question: Does the identified founder effect signature identified correlate with a increase in Fst, compared to close populations without such an effect (or a weaker version)?

    To pick at one example within the Supplementary Table 2, which seems the most dramatic version, there is quite some difference in the magnitude in inferred If % (founder effect) paramater between the “Romania Iron Gates” and “Latvia HG” ancient dna groups from HO42 (10.23% / 6%) and these populations are close to forming a clade. That is quite a dramatic difference relative to the average If % reported.

    But Fst data doesn’t seem to show a dramatic or any systematic increase in Fst for these populations from outgroups (for example African)?

    Made a bunch of plots to try and look at this: https://imgur.com/a/kF4modk . (Albeit I lack the Fst data for most of South Asian populations to compare.) It doesn’t look like groups who are closely related, who they find to have different levels of If% show different Fst to outgroups too much.

    It seems like between sets of ancient populations (e.g. EEF vs HG), those that have higher Fst tend to have more If%, but that within these sets (e.g. within HG), the groups with quite elevated If%, even more dramatic founder effects than seen in South Asia today, no signal of elevated Fst?

    Perhaps the effects are just too small/subtle even from these founder effects to show up in Fst. I wouldn’t have expected that tho.

  3. Different new paper but related to RoH-ish discussions: https://www.cell.com/current-biology/fulltext/S0960-9822(20)31097-6“An increased rate of close-kin unions in the central Andes in the half millennium before European contact”

    Methods from Ringbauer preprint used to find rise of close-kin matings in Andes, under the conditions of decline of larger states in Central Andes, prior to European contact.

    (This precedes rise of Inca state, which is stereotypically, perhaps inaccurately, characterized by descriptions of being more like a functioning command economy than other ancient states. But also description of lineage groups that cross cut different eco-zones in order to pool accessible resources between mountain eco-zones – https://en.wikipedia.org/wiki/Vertical_archipelago“(M)ost highland Andean societies, such as the Quechua and Aymara, were organized into moietal lineage groups, such as ayllus in the Quechua case. These lineages internally shared local labor through a system called mink’a … Absent the use of trade to access resources, economic transactions were essentially intra-lineage obligations of labor. These lineages required a base level of self-sufficiency to achieve autarky. In the Andes, a long mountain range with a great variety of ecozones and resources, the need to access the proper lands for specific crops or animals meant lineages created miniature colonies or sent seasonal migration (such as transhumance) in different ecoregions.”. Though that seems not to have led to any wider Andean homogenization, from Nakatsuka’s paper – https://reich.hms.harvard.edu/sites/reich.hms.harvard.edu/files/inline-files/2020_Nakatsuka_Cell_Andes_0.pdf)

    Kind of maybe useful as a parallel case study to the rise of close-kin mating in Islamic sphere.

  4. So, the article seems to imply that the disease load of Ashkenazim (I’m one) is disproportionate to the founder effect…

    Is a screening bias to blame? Ashkenazim are primarily urban and have good access to / bias towards health care.

  5. The discrepancy with the Ashkenazi Jews is the feature of the algorithm which models a lone founder effect without a post-bottleneck readmixture. Such an admixture is bound to disproportionately dilute LDs between markers, and, if the later admixing group is related to the founder group, to affect the length spectrum of the LDs. These effects are expected to lower the effective strength of the founder effect and to inflate the age of the admixture.

    The post-bottleneck kin-group readmixture is the major feature of the Ashkenazi demographic history, and indeed, the new ASCEND estimates show inflated bottleneck timing (37 generations vs. historically attested ~500 years) as well as unrealistically low severity of the bottleneck effect (1.7% on their scale).

    Unfortunately most of the population geneticists aren’t interested in the details of the serial founder-effect / expansion / readmixture demographic history of the European Jews. They are content with the obsolete books view of the Ashkenazi history as a single leapfrogging “escape to Poland” from the Medieval Rhineland, and they are quick to conclude that an observed, nearly millennium-old “averaged founder effect” roughly coincides with the legendary extermination of the Rhineland Jewry. The actual corpora of the historic evidence on the community make-up, size, and migrations have been systematically studied only in recent decades. They show a repeated cycle of Eastward migration, to Moravia, Poland, and most importantly to the Grand Duchy of Lithuania in the 1500s. The further East the Jews went, the greater potential for the demographic expansion they encountered. While Rhineland and Moravian Jewish populations remained stagnant for centuries, the founders of the Polish and especially Greater Lithuanian communities established fast-growing populations, where initially, the economic opportunities were restricted to the descendants of the founders, but eventually, bidirectional East-West diffusion blurred the boundaries somewhat.

    As a result, most genetic ancestry of the Ashkenazi Jews dated back to the Lithuanian founders (t = 500 ybp, Ne ~ 100 ), even in the West of Europe (where the formerly Lithuanian Jews spread after Prussia annexed their homelands in the 1700s). But much of the genetic diversity has been partly reestablished with the East-West population exchanges with the historically more numerous, but also more stagnant, communities to the West.

    A simplest model to study may be a bifurcated-and-reunited population in which one part experiences neither a bottleneck nor a population growth, while the other. much smaller, part becomes founders of a large, exponentially growing subpopulation before the reunification. Nothing of this sort has been tested AFAIK. Instead, study after study seem to be content with the “effective / compound” single founder effect estimates (older and smaller than the real events). But rare allele frequencies (unlike common-variant LD patterns) are primarily defined by the real, latest founder event, and that’s why the disease variants seem to tell “a different story”.

  6. PS: of course working with Behar’s dataset (disproportionately enriched with Western Ashkenazim and therefore relatively depleted of the “Lithianian founder expansion”) is a sure way to underestimate the severity, and the recentness, of the pan-Ashkenazi founder effects even further.

    Population structure is always important! But when most of the genetic diversity came from one subpopulation, but most of the population size, from the other subpopulation, it just can’t be ignored.

  7. They examine samples from only one province of Turkey, Balıkesir Province, which could still be fine had they not made this general interpretation about Anatolia/Turkey only based on their results:

    We inferred strong founder events in the history of seven West Eurasian present-day populations, including in Western Europe (Basque country and Sardinia), Eastern and Northern Europe (Belarus, Estonia, Finland and Lithuania) and Anatolia (Turkey) (Figure 2). (emphases mine)

  8. “the intensity of a founding event”

    What does that mean? My guess is that it does not have to do with hot sex at an orgy.

  9. Thanks for the replies, folks.

    I don’t know how it is for you folks, but according to 23andme, MH and FTDNA I have hundreds of 2nd cousins — none of whom have any known relationship to me. 🙂

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