The Parsis are about 25% South Asian genetically

parsiMTDNA

parsi2In the comments below I made the comment that the Parsi people of India, who reputedly arrived in India ~1000 years ago from Iran, are about 25 percent South Asian. By this, I mean that their ancestry is about 75 percent Iranian (presumably Persian), with 25 percent admixture from South Asian populations amongst whom they lived. But my feeling about this was vague, and I decided to check the scientific literature. Unfortunately there hasn’t been a lot of work done in this area with cutting edge genomics. But a cursory examination shows that there’s been substantial migration of Indian women into the Parsi lineage via the mtDNA. In the figure to the right you see that “PA”, the Parsis, have a lot of “South Asian” mtDNA lineages compared to the Iranian groups. This mostly consists of South Asian branches of haplogroup M. It jumps out to you immediately when looking at the haplotypes that the Parsis carry on their mtDNA. I found less on the Y chromosomes, which are less informative in differentiated South Asians from Iranians in any case (the mtDNA difference is much greater between these two regions), but what I did find is that Parsis can be modeled as 100% Iranian on their paternal lineages. This is probably an exaggeration, but as a stylized fact I think it gets to the heart of the matter.

But what would really be useful are autosomal results. Those were hard to find. Noah Rosenberg’s 2006 paper on Indian genetic differentiation using microsatellites did have a Parsi sample. If you look at the results the Parsi do seem South Asian, roughly equivalent to Pathans, an Iranian speaking group in Pakistan which has strong South Asian affinities. But the sample set does not include any Iranian groups from Iran proper, but rather Middle Eastern groups from the Arab world or the Caucasus. Without such a reference population it is hard to gauge Parsi relatedness.

There was one last hope. Harappa DNA has been collecting results for many years now, and I was hoping that there was a Parsi in the sample. There was, just one. I took the Parsi and compared this individual to various Iranian and a few select Indian groups. Here are the admixture results (edited to show only the relevant ancestral clusters):

Ethnicity S.Indian Baloch Caucasian NE.Euro Mediterranean SW.Asian
Kurd (Iraqi) 0 29 40 4 6 16
Iraqi Arab 1 11 30 0 5 44
Kurd (Iraqi) 1 26 43 5 5 16
Kurd (Iraqi) 1 28 43 5 5 13
Kurd (Iranian) 1 29 41 7 6 12
Kurd Zaza Turkey 2 23 43 6 6 13
Iranian 2 24 43 5 7 13
Kurd (Turkish) 2 26 46 6 6 10
Iranian 2 28 47 7 3 10
Iranian 2 29 43 3 8 8
Iranian 2 30 44 4 2 13
Iraqi Arab 3 20 39 0 10 19
Kurd Kurmanji Iraq 4 21 41 4 7 15
Kurd from Turkey 4 24 41 4 8 12
Iranian 4 26 39 7 7 12
Kurd Yezidi Iraq 4 26 39 4 7 13
Iranian 4 27 41 5 6 11
Iranian 4 29 37 4 4 12
Iraqi Arab 5 19 38 5 7 19
Kurd Kurmanji Iraq 5 24 39 4 8 13
Iranian 5 25 38 5 7 12
Kurd (Iraqi) 5 27 41 5 5 14
Iranian 6 25 37 6 6 12
Kurd (Feyli) 6 25 38 3 7 14
Iranian Khorasani 8 29 35 9 2 11
Afghan Pashtun 14 32 25 12 3 4
Pashtun (Kandahar) 15 34 25 10 0 5
Mumbai Parsi 16 28 28 5 4 12
Afghan Pashtun 20 36 17 11 0 5
Afghan Pashtun 21 33 17 9 2 2
Pashtun 21 35 18 10 0 5
Gujarati Khoja 28 47 13 7 0 1
Gujarati Patel Muslim 34 32 13 3 3 6
Gujarati Sunni Vohra Surti 35 34 13 5 2 4
Gujarati Ganchi 38 42 5 9 3 0
Gujarati Vaishnav Vania 45 36 4 4 1 3
Gujarati Jain 46 36 6 4 0 0
Gujarati Vaniya 52 37 2 6 0 1
Gujarati 53 43 0 0 2 0
Gujarati 56 39 0 0 2 0

The key is to focus on the “South Indian” ancestry. Though this is found in some Iranian groups, it drops off very rapidly once you move past groups like the Pathans. The Parsi individual has 16 percent South Indian ancestral component. Looking at the Iranian individuals, you can probably say that you might expect 5 percent from this population. The question is what is the Indian source population? There’s a lot of variation among these. But, if you take 50 percent South Indian for the South Asian source population, then you get:

(50 percent)*(0.75) + (5 percent)*(0.25) = 16.25%

So at least going by this one individual something like ~25 percent is probably correct for the Parsis in terms of how much “native” South Asian ancestry they’ve picked up. Since they are genetically quite homogeneous at this point an N = 1 might be sufficient to reach a conclusion. I’d be curious if anyone finds anything different.

The Parsis are about 25% South Asian genetically

parsiMTDNA

parsi2In the comments below I made the comment that the Parsi people of India, who reputedly arrived in India ~1000 years ago from Iran, are about 25 percent South Asian. By this, I mean that their ancestry is about 75 percent Iranian (presumably Persian), with 25 percent admixture from South Asian populations amongst whom they lived. But my feeling about this was vague, and I decided to check the scientific literature. Unfortunately there hasn’t been a lot of work done in this area with cutting edge genomics. But a cursory examination shows that there’s been substantial migration of Indian women into the Parsi lineage via the mtDNA. In the figure to the right you see that “PA”, the Parsis, have a lot of “South Asian” mtDNA lineages compared to the Iranian groups. This mostly consists of South Asian branches of haplogroup M. It jumps out to you immediately when looking at the haplotypes that the Parsis carry on their mtDNA. I found less on the Y chromosomes, which are less informative in differentiated South Asians from Iranians in any case (the mtDNA difference is much greater between these two regions), but what I did find is that Parsis can be modeled as 100% Iranian on their paternal lineages. This is probably an exaggeration, but as a stylized fact I think it gets to the heart of the matter.

But what would really be useful are autosomal results. Those were hard to find. Noah Rosenberg’s 2006 paper on Indian genetic differentiation using microsatellites did have a Parsi sample. If you look at the results the Parsi do seem South Asian, roughly equivalent to Pathans, an Iranian speaking group in Pakistan which has strong South Asian affinities. But the sample set does not include any Iranian groups from Iran proper, but rather Middle Eastern groups from the Arab world or the Caucasus. Without such a reference population it is hard to gauge Parsi relatedness.

There was one last hope. Harappa DNA has been collecting results for many years now, and I was hoping that there was a Parsi in the sample. There was, just one. I took the Parsi and compared this individual to various Iranian and a few select Indian groups. Here are the admixture results (edited to show only the relevant ancestral clusters):

Ethnicity S.Indian Baloch Caucasian NE.Euro Mediterranean SW.Asian
Kurd (Iraqi) 0 29 40 4 6 16
Iraqi Arab 1 11 30 0 5 44
Kurd (Iraqi) 1 26 43 5 5 16
Kurd (Iraqi) 1 28 43 5 5 13
Kurd (Iranian) 1 29 41 7 6 12
Kurd Zaza Turkey 2 23 43 6 6 13
Iranian 2 24 43 5 7 13
Kurd (Turkish) 2 26 46 6 6 10
Iranian 2 28 47 7 3 10
Iranian 2 29 43 3 8 8
Iranian 2 30 44 4 2 13
Iraqi Arab 3 20 39 0 10 19
Kurd Kurmanji Iraq 4 21 41 4 7 15
Kurd from Turkey 4 24 41 4 8 12
Iranian 4 26 39 7 7 12
Kurd Yezidi Iraq 4 26 39 4 7 13
Iranian 4 27 41 5 6 11
Iranian 4 29 37 4 4 12
Iraqi Arab 5 19 38 5 7 19
Kurd Kurmanji Iraq 5 24 39 4 8 13
Iranian 5 25 38 5 7 12
Kurd (Iraqi) 5 27 41 5 5 14
Iranian 6 25 37 6 6 12
Kurd (Feyli) 6 25 38 3 7 14
Iranian Khorasani 8 29 35 9 2 11
Afghan Pashtun 14 32 25 12 3 4
Pashtun (Kandahar) 15 34 25 10 0 5
Mumbai Parsi 16 28 28 5 4 12
Afghan Pashtun 20 36 17 11 0 5
Afghan Pashtun 21 33 17 9 2 2
Pashtun 21 35 18 10 0 5
Gujarati Khoja 28 47 13 7 0 1
Gujarati Patel Muslim 34 32 13 3 3 6
Gujarati Sunni Vohra Surti 35 34 13 5 2 4
Gujarati Ganchi 38 42 5 9 3 0
Gujarati Vaishnav Vania 45 36 4 4 1 3
Gujarati Jain 46 36 6 4 0 0
Gujarati Vaniya 52 37 2 6 0 1
Gujarati 53 43 0 0 2 0
Gujarati 56 39 0 0 2 0

The key is to focus on the “South Indian” ancestry. Though this is found in some Iranian groups, it drops off very rapidly once you move past groups like the Pathans. The Parsi individual has 16 percent South Indian ancestral component. Looking at the Iranian individuals, you can probably say that you might expect 5 percent from this population. The question is what is the Indian source population? There’s a lot of variation among these. But, if you take 50 percent South Indian for the South Asian source population, then you get:

(50 percent)*(0.75) + (5 percent)*(0.25) = 16.25%

So at least going by this one individual something like ~25 percent is probably correct for the Parsis in terms of how much “native” South Asian ancestry they’ve picked up. Since they are genetically quite homogeneous at this point an N = 1 might be sufficient to reach a conclusion. I’d be curious if anyone finds anything different.

Open Thread, 1/25/2015

9780307823069_p0_v1_s260x420My intention was to read Ian Morris’ War! What Is It Good For?, but I’ve decided on Jonathan Spence’s Emperor of China: Self-Portrait of K’ang-Hsi. I’ve had this book for about seven years, and haven’t gotten to it, but now is a good time since I’ll be tackling Marcus Aurelius: A Life, and Meditations. The relationship between these two topics should be obvious to most readers with some familiarity with history.51NPyQMF0jLSimultaneous to this I’m reading The Northern Crusades on the Kindle. I got about 25% of the way through this book at some point, but had to set it aside. But the history of the Baltic has always been fascinating to me, and I think it’s an interesting topic. Most people seem unaware that the Crusades occurred in northeast Europe as well as the Levant, and that they lasted in active form longer in the north than in the Middle East.

I’ve been considering the role of specialization in science recently. Obviously I’m interested in genetics, and that has sharply constrained by knowledge of the literature. Even within genetics I’m fixated on the topics of evolutionary genomics, with a focus on humans and other mammals. When I was younger my interests were far more catholic, though I don’t know what I can do about this evolution in my focus at this point. We all go through phases, and perhaps in the future can I branch out again.

Finally, can readers people stop leaving comments with the handle “anon” or “anonymous.” I don’t mind if you have these terms in the name, but it gets very difficult to follow people if there are six or seven different individuals who go by “anon.”

The Houthi are the most like Sunnis of the Shia

Islam_branches_and_schools.svg
The New York Times has a piece within the title Experts See Signs of Moderation Despite Houthis’ Harsh Slogans. It mulls over the fact that the Houthi rebels, who are rapidly becoming the establishment, brandish anti-American and anti-Israeli slogans, and are clearly getting Iranian money. The piece mentions that the Houthi rebels are Zaydi, which is a branch of Shia Islam. But to me the article tip-toes around a somewhat important point about Zaydi Shia Islam: it is usually considered the most “Sunni-like” of all the Shia sects. One of the aspects of John Walker Lindh’s biography was that when he was in Yemen he was offended that Sunni and Shia prayed in the same mosques on occasion. This reflects the fact that Zaydi are not as deviated in practice from Sunni Muslims as other Shia. In the article there the question of an analogy to Hezbollah:

“The Houthis are not Hezbollah,” said Charles Schmitz, an expert on the group and a professor at Towson University, referring to the Iranian-supported group that dominates Lebanon and is actively fighting on behalf of President Bashar al-Assad in Syria. “They are domestic, homegrown, and have very deep roots in Yemen, going back thousands of years.”

All true. But I think it needs to be emphasized that Hezbollah espouses the same Twelve Shia religion as Iran, and the connections between these two groups is historically very deep. The conversion of Iran to Twelver Shia Islam occurred in the 16th century under the direction of ulema imported from southern Lebanon, basically the same group which has supported the rise of Hezbollah. The reciporcal exchange of ulema between this region and Iran has continued down to the present day (see The Shia Revival by Vali Nasr). Any attempt to connect the Houthi to Iran has to be careful, emphasizing the situational aspect of this relationship when compared to Hezbollah. Because of Hezbollah’s ideological and historical identity with the Iranian religious order it is hard to ever imagine a scenario where it acts counter to Iranian interests. This is not the case with other groups which allied with Iran, such as the Assad regime, whose Alawite sect is only nominally Twelver (due to some political machinations in the 1970s), or the Houthi, whose Zaydi sect was the dominant one within Shia Islam for many hundreds of years before the conversion of Iran to the Twelver set.

Western liberals are the WEIRDist

41DV5KYNJALA friend passed me this ScienceDaily press release, American liberals and conservatives think as if from different cultures. I suspected that Jon Haidt was on the paper, and I was right, Liberals Think More Analytically (More “WEIRD”) Than Conservatives. Reading the paper the major finding seems to be that Western social liberals, and especially libertarians, exhibit the tendencies which have been defined as “WEIRD”: Western, educated, industrialized, rich, and democratic. In contrast, social conservatives in the West are less WEIRD, and tend to resemble non-Western cultures in cognitive style.

The way that this paper dichotomizes the classes is that the WEIRD tends to be more “analytic” and non-WEIRD more “holistic.” The terminology here is often freighted, and I’be cautious about overemphasizing that aspect. Rather, the key here is that in terms of traits you see a pattern where Western liberals are to a great extent the tail of a particular distribution of mental styles. To illustrate the analytic style of reasoning Joshua Greene, the author of Moral Tribes: Emotion, Reason, and the Gap Between Us and Them, has argued that incest taboos are based on disgust and reflex, rather than reason (or, the reasons are rationalizations). And, that this is clearly from his perspective not a good thing. That is the classic WEIRD tendency; to decompose the broader issue into its parts, and reach logical conclusions, even if they seem absurd or repulsive, and embrace them. Brian Williams is also WEIRD. Very WEIRD.

1361104223In the above paper they use samples of college students at University of Virginia, those who participated in the moral foundations survey, and a few thousand Chinese students, to test their model. Though the correlations in most cases were modest (e.g., on the order of 0.2 to 0.4), it seems clear from their data that a left-right social orientation can map mapped onto differences in analytic vs. holistic thinking across cultures, and also reflect differences between cultures. Chinese college students raised in urban areas were more analytic if socially liberal. Western college students were more holistic if socially conservative.

I don’t think any of this is going to shock or surprise anyone. Rather, the interesting part to me is how easily it maps onto pattern discerned by the psychological Richard Nisbett, and reported in his book The Geographic of Thought: How Asians and Westerners Think Differently…and Why. Nisbett reported a pattern which in today’s language would have a continuum of WEIRDness like so: Anglosphere & Norden > Continental Europe > rest of the world. These data in that framework suggests that even within the Anglosphere, which is dominated by WEIRD thought, there are a large reservoir of people who reject that paradigm in their daily life. In addition, the correlation with length of time post-industrial, as well as the fact that the tendencies toward WEIRDness are now cropping up in East Asia as well, suggest that in some ways a Whiggish model is broadly correct. Nisbett and Haidt’s group both report that it isn’t particularly difficult to prime individuals to switch from one mode of cognitive style to another.

Finally, many social liberals look at social conservatives as being backward, and in need of being “educated” and “ignorant.” There’s some descriptive truth in this, insofar as there’s a fair amount of evidence that social conservatism is negatively correlated with intelligence and education. But, one can also look at social conservatives as a different culture, as simply not WEIRD. This puts modern social liberals in somewhat of a bind if they are multicultural, because perhaps they are now enjoined to extend their tolerance of other cultures to social conservatives? OK, forget about that.

The search for Indo-Europeans in comment sections

horsewheellanguageDavid Reich and Nick Patterson come down in favor of the steppe as the ur-heimat of the Indo-Europeans, at least those who migrated into Europe, in a recent abstract:

We generated genome-wide data from 65 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of about 390,000 single nucleotide polymorphisms. This strategy decreases the sequencing required to obtain genome-wide data from ancient DNA samples by around 1000-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that in western Europe, the farmers of both Germany and Spain >7,000 years ago were descended from a common ancestral stock. These farmers did not replace the earlier hunter-gatherers, but continued to mix with them, leading to a resurgence of hunter-gatherer ancestry in both Germany and Spain ~1,000-2,000 years later. In eastern Europe, the hunter-gatherers of Russia >7,000 years ago were distinct from those of the west, having an increased affinity to a ~24,000 year old individual from Siberia, but this affinity was reduced by ~5,000 years ago in the Yamnaya steppe pastoralists because of admixture with a population of Near Eastern ancestry. Western and Eastern Europe collided ~4,500 years ago with the appearance of the Corded Ware people in Central Europe, who derived at least two thirds of their ancestry from an eastern population closely related to the Yamnaya. The evidence for mass migration into Europe thousands of years after the arrival of agriculture, in combination with linguistic and archaeological data, makes a compelling case for the steppe as a proximate source for the spread of Indo-European languages into Europe.

This is broadly the same data which Iosif Lazaridis presented at ASHG 2014. So this itself is not new. But what I would like to draw your attention to are two posts over at Eurogenes, Ancient DNA points to the Eurasian steppe as a proximate source for Indo-European migrations into Europe, and Yamnaya genomes are a 50/50 mix of eastern Euro foragers and something else ANE-rich. Nick Patterson actually weighed in over in the comment thread for the first post. A comment in the second post was especially amusing:

Over 400 comments on an abstract? You may need to start a forum when the actual paper is released, David.

insearchofYes, there were over 400 comments on the first post. It shows you how passionate people get about this issue. Some of the associations within this field are of a racialist nature. The Journal of Indo-European Studies was founded by Roger Pearson, though today it is edited by the respectable J. P. Mallory. This is not to say that all of those enthusiastic about this topic are quite so “out there,” but it’s quite emotional.

Until the paper itself comes out I suggest readers bone up on the archaeology, because there’s a wealth of that out there already. From what I recall the Samara samples were form David Anthony, and his The Horse, the Wheel, and Language: How Bronze-Age Riders from the Eurasian Steppes Shaped the Modern World is basically required reading in my opinion if you are interested in this issue. Also, Mallory’s older In Search of Indo-Europeans is probably worth reading as well. We live in interesting times indeed!

The search for Indo-Europeans in comment sections

horsewheellanguageDavid Reich and Nick Patterson come down in favor of the steppe as the ur-heimat of the Indo-Europeans, at least those who migrated into Europe, in a recent abstract:

We generated genome-wide data from 65 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of about 390,000 single nucleotide polymorphisms. This strategy decreases the sequencing required to obtain genome-wide data from ancient DNA samples by around 1000-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that in western Europe, the farmers of both Germany and Spain >7,000 years ago were descended from a common ancestral stock. These farmers did not replace the earlier hunter-gatherers, but continued to mix with them, leading to a resurgence of hunter-gatherer ancestry in both Germany and Spain ~1,000-2,000 years later. In eastern Europe, the hunter-gatherers of Russia >7,000 years ago were distinct from those of the west, having an increased affinity to a ~24,000 year old individual from Siberia, but this affinity was reduced by ~5,000 years ago in the Yamnaya steppe pastoralists because of admixture with a population of Near Eastern ancestry. Western and Eastern Europe collided ~4,500 years ago with the appearance of the Corded Ware people in Central Europe, who derived at least two thirds of their ancestry from an eastern population closely related to the Yamnaya. The evidence for mass migration into Europe thousands of years after the arrival of agriculture, in combination with linguistic and archaeological data, makes a compelling case for the steppe as a proximate source for the spread of Indo-European languages into Europe.

This is broadly the same data which Iosif Lazaridis presented at ASHG 2014. So this itself is not new. But what I would like to draw your attention to are two posts over at Eurogenes, Ancient DNA points to the Eurasian steppe as a proximate source for Indo-European migrations into Europe, and Yamnaya genomes are a 50/50 mix of eastern Euro foragers and something else ANE-rich. Nick Patterson actually weighed in over in the comment thread for the first post. A comment in the second post was especially amusing:

Over 400 comments on an abstract? You may need to start a forum when the actual paper is released, David.

insearchofYes, there were over 400 comments on the first post. It shows you how passionate people get about this issue. Some of the associations within this field are of a racialist nature. The Journal of Indo-European Studies was founded by Roger Pearson, though today it is edited by the respectable J. P. Mallory. This is not to say that all of those enthusiastic about this topic are quite so “out there,” but it’s quite emotional.

Until the paper itself comes out I suggest readers bone up on the archaeology, because there’s a wealth of that out there already. From what I recall the Samara samples were form David Anthony, and his The Horse, the Wheel, and Language: How Bronze-Age Riders from the Eurasian Steppes Shaped the Modern World is basically required reading in my opinion if you are interested in this issue. Also, Mallory’s older In Search of Indo-Europeans is probably worth reading as well. We live in interesting times indeed!

Toward discovering genes affecting cognition

Citation: Common genetic variants influence human subcortical brain structures, Nature (2015) doi:10.1038/nature14101

Citation: Common genetic variants influence human subcortical brain structures, Nature (2015) doi:10.1038/nature14101

Here’s what we know. Intelligence, as defined by a general factor which explains variation across a range of cognitive tasks, is substantially heritable, with a narrow sense heritability on the order of 0.25 to 0.75 depending on who you talk to and what context.* Intelligence itself exhibits correlations with other traits, from those of social important, such as education, as well as biological parameters, such as brain size. Additionally, the effect size of genetic variations associated with general intelligence are likely to be very small. This means that you should be immediately skeptical of claims that a common variant segregation in the population explains a large proportion of the variation in intelligence within the population. The history of this area of research, which goes back to linkage studies, is one of non-reproducibility. Large effect quantitative trait loci should already have been picked up by linkage studies decades ago, so I am usually rather skeptical when this old wine is presented again in a genomic guise. In short, the genetic architecture of general intelligence is likely to resemble height, with many loci of small effect.**

This is what Rietveld et al. found last fall in Common genetic variants associated with cognitive performance identified using the proxy-phenotype method. The same sizes were on the order of 10,000 to 100,000 within this study. The top associations within this study explain less than 1% of the variation within the data. It seems likely that the largest effect alleles which influence intelligence variation are about an order of magnitude smaller in impact than those for height. A new paper in Nature, Common genetic variants influence human subcortical brain structures, looks at the morphology of the brain, synthesizing imaging, cognitive neuroscience, and genomics. Here’s the abstract:

…To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

Paul Thompson was involved in the research, so I am confident that it was be done thoroughly (and the author list is long enough that I hope they checked for obvious problems!). To correct for population stratification within this European sample they looked at the top for dimensions of variation, and used a regression model to capture other variables which might be confounded with the SNPs in question. The small proportion of variation explained actually increases my confidence, in that it seems to be in the same order of magnitude as the type of studies looking at endophenotypes.

Because of their sheer number I doubt that there’s a great short term likelihood of annotating all the genes responsible for variation in intelligence. Rather, I wonder if the ultimate goal is something similar to what occurred with statins. Find a small effect locus, and target a drug at that locus to help cure cognitive illnesses such as schizophrenia. It stands to reason that the same loci which impact general intelligence would also shape cognitive phenotypes which we term pathological.

* So if heritability in the narrow sense is 0.50 that means half the variation in intelligence in the population can be explained by variation of genes in the population. By way of comparison, height is 0.80 to 0.90 heritable in the narrow sense in the developed world. This does not mean that the correlation between parents and offspring is 0.80 or 0.90 for height. In fact the correlation is closer to 0.50 for height between parents and offspring and also between siblings.

** An alternative minority viewpoint is many rare alleles of somewhat larger effect.

The young do not support abortion rights inordinately

A few weeks ago I wrote on something on the data on abortion views for The New York Times. The main reason is because of the sort of commentary which is now percolating through the media in response to some abortion related legislation. In particular, the implicitly liberal media.* As an example of what I mean, Donald Graham in The Atlantic has a piece titled The Republican Party’s Abortion Bind: Female GOP lawmakers withdrew their support for a late-term ban, demonstrating that the leadership is more than just old, white men. Notice the subhead here, the reference to “old, white men” is the trope which is regularly trotted out. But as I showed in my piece above there’s no sex difference on the whole when it comes to abortion, though conservative women are more likely to be pro-life than conservative men. Graham suggests that “female Republican lawmakers…worried that the rape-reporting restriction was too strict, and that the bill would alienate young voters and women from the party.” From other reporting this is the perception of the lawmakers. Graham also makes an allusion to the fact “everyone knows the GOP faces a demographic time bomb, since its voters are older and whiter and more pro-life than the general population, so it’s risky to do anything that might make it harder to win them over.” Yet despite relaying that some Republican lawmakers think the abortion issue alienates younger voters, he acknowledges that that’s not the case, stating that “It’s a surprising and little-known fact that opinions about abortion have barely budged in the American public in the 42 years since Roe.” If there was a major secular age effect then attitudes toward abortion would change over time as older cohorts died.

There has been trend in recent years for liberal commentators to decry the fact that the media relays the opinions of politicians without scrutinizing their factual content. But that’s somewhat selective. Here is a case where a group of Republican lawmakers are expressing opinions based on facts which are simply not true. Either they know they are not true, or they are not aware of the facts. The media should perhaps enlighten them. But they’re not, because as it happens the reality is most of the media is not sympathetic to the pro-life position.

Here are the facts, as told by Gallup (found with something called Google) and the General Social Survey. From Gallup a few years back, Generational Differences on Abortion Narrow: Support for making abortion broadly illegal growing fastest among young adults. The results show a small trend toward millenials being less supportive of abortion rights than previous generations. I wouldn’t make too big of a deal about this, because the differences are often not that great. But, the trend is real. Rather than being monotonic, there is a pro-choice “peak” among late boomers and gen-Xers, with the oldest cohorts being the most pro-life, but the youngest ones being next in line.

CatusWildAutoCluster_htm_m2d838ae4I repeated the analysis using the “ABANY” variable in the GSS, comparing to age cohorts from 1931 onward. What you can see is that the most pro-choice voters were born between 1951 and 1970. There has been a shift back toward more pro-life positions on the part of gen-Xers, and even more among millenials.

So the young do not support abortion rights to a greater extent than the older cohorts, unless you are talking about senior citizens, though soon enough the most pro-choice generations will actually fall into that category. The more interesting question is why some Republicans often bring up these sorts of talking points whenever push comes to shove on social issues which they purportedly support. Even granting the sincerity of the pro-life views of many Republicans, I think the issue is that it’s really not something they want to get into a war over, because it’s not a primary concern for most of the party. They rely on social conservatives, and so faithfully and stridently pay lip service to their concerns, but generally balk at toughing it out when it comes to legislation.

In the end I think Jon Chait is right in his polemic The Big Con. Economic conservatives call the final shots, and get results. Republicans oppose tax increases on “job creators” passionately. When it comes to legislation around abortion a large portion of the party heads for the hills.

* Here I’m not talking about Mother Jones, but more mainstream journals. Though most of their writers do not take strident liberal positions, they are personally social liberals, and this usually shows. What set of issues do you think the Republican party would shut the government down over?

Single markers tell you only a bit about individual ancestry

Citation: Estimates of Continental Ancestry Vary Widely among Individuals with the Same mtDNA Haplogroup

Citation: Estimates of Continental Ancestry Vary Widely among Individuals with the Same mtDNA Haplogroup

A new paper in The American Journal of Human Genetics, Estimates of Continental Ancestry Vary Widely among Individuals with the Same mtDNA Haplogroup, tells you something which should be obvious:one marker tells you only so much about individual ancestry. In other words, the history of one gene can only tell you so much about the whole genome. Because mtDNA and Y chromosome* does not recombine you can treat it as one long genetic marker. On the coarse grain they can tell us a great deal. Both mtDNA and Y confirmed that it seems the modern human populations seem to be diverged from a group with an African origin. Genomics, even using the whole genome, has confirmed this. Additionally, non-recombining regions of the genome are more tractable for a coalescent framework. They are actually trees.

But Richard Lewontin’s insight that a great deal of human genetic variation is not partitioned across populations, but within them, applies to mtDNA and the Y chromosomes as well. Where Lewontin’s insight misleads is that using just a few more markers one can obtain relatively robust phylogenetic trees which reflect well the population structure and history of a given species. One can see this when one considers mtDNA and Y chromosomal lineages jointly. If someone tells you that their Y chromosomal lineage is R1a1a you can infer that their ancestry is anywhere from Central Europe all the way to South Asia. But if they add that their mtDNA is U2b you can be confident that they are South Asian. U2b spans South Asia, as well as parts of the Middle East. But in the latter zones R1a1a is very rare.

Though the phylogeographic import of mtDNA for a given individual is often questionable, that’s true of any marker. Because mtDNA is amenable to phylogenetic modelling it is still quite useful, especially when making very geographically coarse inferences. But the paper’s argument that the geographic inferences of DTC tests is questionable based on the fact autosomal SNP-chips are the same framework used within the paper to test the informativeness of mtDNA.**

* The NRY

** Disclosure, I have done consulting for Family Tree DNA on their autosomal tests.

Institutions usually beat genius

51Jb17R6p6L._SY344_BO1,204,203,200_Adrian Goldsworthy’s The Fall of Carthage: The Punic Wars 265-146BC is illustrated on its cover with a photograph of a bust of Hannibal Barca. As you may know Hannibal was the general who led the armies of Carthage in the Italian peninsula during the Second Punic War, to great effect. In fact, until the battle of Zama in North Africa, during the last phases of the war, Hannibal did not lose to a Roman army. And yet despite his record of victory in tactical engagements, he was strategically bested by the Romans and lost the war. If there is one figure who looms large in the narrative of The Fall of Carthage it is Hannibal. This is striking because almost all of what we know about these wars comes down to us thanks to the Romans, so our perceptions are coloured by their biases. And yet it is undeniable that Hannibal’s raw tactical genius won grudging admiration and respect from the Romans. He was a singular figure, with no equivalent among the Romans of his era, with all due apologies to Scipio Africanus. And yet Rome won, and Carthage lost.

9780300137194Goldsworthy is a military historian, so I was aware that he would focus on the minutiae of military logistics as well as outlining numerous set piece battles. Much of his How Rome Fell dealt with the slow decay of the Roman military system of the early empire over the course of the 3rd century, and the reorganization of the 4th century, which temporarily halted the decline, while ultimately undermining it in the long term through a reliance on allies who exhibited less attachment to Romanitas. One could argue in many ways the late Roman military complex resembled that of Carthage more than that of Rome during the late republic and early empire. Though the author gives much space to battles and campaigns, aside from the incredible retelling of the Battle of Cannae, one can gloss over the details without loss of the general thrust of the narrative. Battles are won and lost, but the lessons from the war can not be reduced down to the battles.

historyofromeIt was simply improbable that Carthage could win a military conflict with Rome over the long run because the Roman system conferred upon the Roman state material and ideological advantages which could not be overcome by military victories. The Hellenistic general Pyrrhus learned this, and gave us the term “pyrrhic victory”. In ideological terms Goldsworthy argues that the Roman mindset was one where conflicts were viewed as wars of attrition. According to Goldsworthy Carthage, like the Hellenistic states, operated in a more classical Westphalian framework where victory and defeat were never final, but simply instances of a continuous game between elites of distinct polities. But, if it was not for the material advantages of the Roman system its ideological orientation would have been suicidal, because wars of attrition can only be maintained when there are resources to feed them. The Romans relied upon conscript armies of free peasantry, committed to the idea of their republic as an expression of collective will, as well as Italian allies of long standing. Goldsworthy notes that no individual of the Roman elite betrayed their city, no did any of the Latin allies (the cities who went over to Hannibal during his years in Italy tended to be culturally distant from Rome). And, the citizen base of Rome was notoriously broad, because the Roman system was expansive, assimilating allies and elites of foreign cities over time. This is an ancient feature of Roman society, as at least half of the major patrician lineages are not Latin, but Sabine. This is in contrast to organization of Hellenistic or Carthaginian polities, which were not assimilative, but multicultural and cosmopolitan in a manner more resembling the later Roman system of the imperial period, or empires more generally.* The armies of Carthage and the Hellenistic kingdoms were not manned by citizens, but professionals, whether a standing army, or mercenaries and subject peoples. The army deployed by Hannibal consisted of Libyans and Spaniards, as well as other assorted hirelings. Until the last of the conflicts between Rome and Carthage, which took place in the immediate environs of Carthage, Roman amateur soldiers lined up against armies in the service of Carthage, not armies of Carthaginians.

warinhumancivilizationThe robustness of the Roman system to defeat can be put down to the fact that like the armies of the French Revolution Rome threw its citizenry against its enemies, who purchased smaller professional armies. In many circumstances these professionals could obtain victory, but the gains did not have the depth to force the concession of the Roman state, because the state was an expression of the populace, which remained defiant. In Azar Gat’s expansive War in Human Civilization the author reports that numbers are the number one predictor of victory in battle and war. In other words, the side that can throw more resources into the conflict can win if it so chooses. Sometimes those resources are not so easy to simply measure. For example, Britain’s rise to power in the 18th century has often been attributed to its ability to borrow money to finance its wars (in contrast, many continental polities were not as creditworthy, and so lacked as many financial resources). There are cases where individuals of particular genius and charisma can change the calculus; Gat for example states that Napoleon Bonaparte’s armies were as successful of forces which were nearly 30% bigger. In other words, Napoleon’s particular genius was worth a third again as many soldiers as he actually had at his disposal. And yet ultimately Napoleon lost his wars in the end. The French innovation of conscripting the whole nation for war could only gain them advantages for so long as other Europeans nations caught up, and ultimately surpassed them in raw quantity.

warandpeaceandwarUltimately the particular story in The Fall of Carthage dovetails perfectly with the general model in Peter Turchin’s War and Peace and War: The Rise and Fall of Empires. The Romans of the republic had asabiyah, social cohesion. Against their enemies they exhibited a stance where they accepted that the only alternatives were collective victory or collective extinction. One can speculate why this was so, but clearly that is the key variable in the rise of Rome in the world after the death of Alexander. And it explains the fall of Carthage, which in many ways was a Hellenistic polity, rather than an heir to the ancient traditions of the Levant. In the sense of microeconomics the Carthaginians were homo economicus in comparison to the Romans. The years before the Third Punic War were ones of incredible prosperity for the city of Carthage, as documented in the Roman literary sources as well as archaeology. Rome fought Carthage not because it was weak and poor, but because it was strong and rich. And Rome won because its citizens loved their city more than could be accounted for by any rational calculation.

* Because history is written by the winners we have little direct documentation from Carthage, but it is noteworthy that the city seems to have resembled Rome’s mixed system of governance, down to having a senate.

Native Americans are evolutionary experiments

James C. Chatters 2002 book

James C. Chatters 2002 book

By now you may have read the breaking news in The Seattle Times that Eske Willerslev’s group is going to publish genetic results on Kennewick Man. This “scoop” was obtained through the freedom of information act, which makes sense since Kennewick Man has been embroiled in political controversy since the beginning of it’s discovery by James Chatters in the 1990s. The issue is that morphologically the remains were not typical of contemporary Native Americans, which might cause some doubt as to the legitimacy of the social-political rights of the indigenous people of the region today. The social-political aspects have been beaten to death, and I am not particularly interested in that area. Rather, the science is more fascinating, if, somewhat less surprising in light of the results that are going to come out in the near future.

2019387254The most famous reconstruction of Kennewick Man is strange because it resembles British actor Patrick Stewart. Humans use phenotypes, morphology, to ascertain genetic relatedness when DNA is not available. In the 1990s DNA was not available. The inference by many researchers who had access to the remains was that Kennewick Man was different because his morphology may have resembled a person of European heritage. The controversy turned into such a circus that somehow Steve McNallen, arguably America’s foremost Northern European neo-pagan expositor, made claims on the remains on the same grounds as Native American people! Later scholars suggest that perhaps Kennewick Man was not so much European, as not typical of contemporary Native Americans (e.g., perhaps he was part of an early migration of basal East Eurasians related to the Jomon of Japan).

41VAznr2aiL._SX258_BO1,204,203,200_If the Seattle Times report is correct, and I believe it is, Kennewick Man is part of the ancestral population to modern Native Americans. This should put to bed most of the political debate, since the results are likely to mollify many Native activists. But, there are still details to be fleshed out. A 2012 publication suggests that there was a secondary migration out of Eurasia, which resulted in the Na-Dene group which is common in the northern and western portions of North America. In contrast, Kennewick Man is likely to belong to the first ur-North Americans, who arrived as a relatively small population from Berengia ~15,000 years ago. This is the overwhelming majority of indigenous ancestry, and south of the Rio Grande basically the totality.*

Due for an update!

Due for an update!

The context here is important. One insight of modern ancient DNA is that there has been a great deal of population turnover over the past ~10,000 years, as well as admixture between disparate lineages. When Kennewick Man died ~9,000 years ago Europeans we understand them did not exist genetically. All across Eurasia, Africa, and Oceania, the Holocene brought radical demographic turnover (with some exceptions such as the Andaman Islands and the deserts of southwest Africa). The New World was somewhat different, as I implied above. Though there were some demographic disruptions, but south of the Rio Grande, and across the eastern half of North America, the populations descend from a relatively homogeneous founder stock which arrived at the end of the Pleistocene. The fact that many remains seem “atypical” for the morphology of Native Americans is strong evidence of in situ evolution.**

Years ago a physical anthropologist told me that when you look at Amazonian natives they “looked” like Siberians. Yes, they had changed and adapted, but only somewhat. It illustrated to me the powerful constraint of limited genetic variation upon populations. Similarly, though there is variation in pigmentation among native populations in the New World, it is far less than you see in the Old World. Why? Perhaps it is a function of different (or lack thereof) of selective pressures. Or, perhaps the variation wasn’t there for selection in the first place? The history of the Old World has jumbled all our easy narratives.  The New World may actually be a godsend because of the simple elegance of its demographic history.

* From my Twitter exchanges with Pontus Skoglund I believe there is some population structure in the founding “First American” group, though not a great deal.

** Admixture is an issue, but that can be obviated by genetic testing, as well as looking at early modern remains.

Where Californians are not immunized

It looks like a combination of the top and low ends of the socioeconomic distribution, Geographic clusters of underimmunization identified in Northern California:

Underimmunization ranged from 18 percent to 23 percent within clusters, compared with 11 percent outside clusters. Between 2010 and 2012, geographic clusters of underimmunization were found in:

  • the East Bay (Richmond to San Leandro);
  • Sonoma and Napa counties;
  • a small area of east Sacramento;
  • northern San Francisco and southern Marin counties; and
  • a small area of Vallejo.

“Shot limiting,” in which parents limit the number of injections or antigens that children receive during a pediatric visit to two or fewer, was found to cluster in similar areas.

Vaccine refusal ranged from 5.5 percent to 13.5 percent within clusters, compared with 2.6 percent outside clusters. Between 2010 and 2012, geographic clusters of vaccine refusal were found in:

  • the East Bay (El Cerrito to Alameda);
  • Marin and southwest Sonoma counties;
  • northeastern San Francisco;
  • northeastern Sacramento County and Roseville; and
  • a small area south of Sacramento

The paper is not live, but it will be here at some point. In Southern California most of the resistance has been in affluent areas, and in some of these areas the fraction immunized is definitely below the herd immunity threshold. Though this trend looks like it may finally have levelled off in California.

Recombination also evolves

recomb2I’m someone who until a few years ago thought of recombination as a pretty boring and static evolutionary genetic parameter. Then I went to a talk by John Novembre which reported on variation between human populations in patterns of recombination (in particular, differences in “hotspots”). For a quick review recombination is important for two primary reasons. One is molecular genetic, insofar as it seems to have structural value for meiotic process and DNA repair. No recombination is generally not good. Second, recombination maintains the law of independent assortment of traits even on the same chromosome, because over time even nearby genes will be uncoupled in their inheritance due to crossing over. From an evolutionary perspective this is important because in this way “good” and “bad” alleles can be decoupled from other other. Recombination is basically a way to enhance the ability of sex to mix and match variation.

Graham Coop revealed patterns of variation among individuals years ago. For example, it is from Graham’s work that I came to understand to recombination is less common in sperm than in eggs, ergo, you’ll have more variance in genomic contributions from paternal than maternal grandparents. Recently at BAPG XI Laurie Stevison presented work reveal patterns of recombination variation, and the role of PRDM9, across great ape lineages. I tweeted some of the results out, but there were a lot of them. I found the talk interesting, but difficult to take in because there was so much. Now Stevison has put out a preprint, The Time-Scale of Recombination Rate Evolution in Great Apes, and I feel somewhat the same about it. There’s lots of good stuff, but unless you are steeped in this domain it is somewhat difficult to parse it and tease out distinct threads coherently. But, as you can tell from the figure at the top of this post changes in patterns of recombination vary as a linear function of genetic divergence. Some of this stands to reason as the karyotypes of great apes differ. And yet even taking this into account it seems there are differences in patterns such as skew of recombination across the genome (e.g., ~75% of the recombination in human genomes occurs on ~20% of the sequence, with enrichment around telomeres, and very little around centromeres). Looking over Stevison’s preprint I have to wonder as to the role of quality of data in some of the results. Genetic maps are hard to get in some populations, and the ones floating around are not always good. The big takeaway of note for me is that though there is lots of variation in fine scale recombination patterns, there are some broad constraints. That makes sense when you note that there are structural/mechanistic reasons for recombination rooted in the nature of meiosis. It’s not a totally neutral parameter which can explore the full space of possibilities. But, in this context obviously the variation in hotspots shows that there are different ways to skin this cat.

Finally, there’s one issue that jumped out at me, and that is they found that “European human population presents the strongest hotspot usage across the genome.” This aligns with earlier work. But I wonder how much of this tendency to find uniqueness in Europeans is due to the enormous amount of genomic resources available for this population. It’s also intriguing in light of the evidence that the European mutation spectrum is different.

In any case, I think everyone should read this preprint several times. I know I’m going to.

The great Eurasian gap

EurasiaRR

slc24a5

SLC24A5 alleles

Many years ago I was perplexed by particular patterns in some genes which have been subject to very strong selection. In particular, the locus SLC24A5 has been subject to a powerful sweep over the last 10,000 years across Western Eurasia, to near total fixation in Europe, but still at high frequencies as far south as India. Yet the derived variant is relatively uncommon in East Asia. Groups which carry the West Eurasian variant, such as the Uyghurs, almost certainly obtained it through admixture processes over the last 10,000 years (in the case of the Uyghurs and various northeast Eurasian ethnicities such as the Mongols, this admixture from West Eurasians is mostly in historical time over the past 2,000 years).

The common sense explanation is that vast regions of interior Eurasia were not highly populated for tens of thousands of years. Even after the Ice Age retreated the Eurasian interior would have been particular inhospitable. Though maps of human migration show where humans have lived at some frequency all across the world, they do not usually show any sign of the density. If densities were low enough in the inter-montane zones of Inner Asia, then for all practical purposes the idea of isolation-by-distance gene flow may not have held for the two antipodes of Eurasia for much of the Pleistocene and early Holocene. So have things changed? I believe so. And it comes down to agriculture, which enabled much higher population densities in areas which were previously simply not feasible areas for hunter-gatherers.

A new paper in Science outlines this for Tibet, Agriculture facilitated permanent human occupation of the Tibetan Plateau after 3600 B.P.. I’ll quote the relevant sections of the paper:

On the basis of the above evidence, the prehistoric human occupation of the NETP can be subdivided into three phases. During the first phase (pre–5200 cal yr B.P.), hunter-gatherers made occasional forays to altitudes reaching above 4300 masl, presumably tracking game. During the second phase (5200 to 3600 cal yr B.P.), a longstanding tradition of millet farming that had become widely established along the middle and lower reaches of the Yellow River extended upstream into the NETP. Millet farming had spread across the Loess Plateau after 5900 cal yr B.P. (17) and subsequently spread across these lower reaches of the NETP from 5200 cal yr B.P. Toward the end of the second phase (4000 and 3600 cal yr B.P.), two significant additions are observed in the crop repertoire (text S4 and fig. S6). The North Chinese crops of broomcorn and foxtail millet were joined or displaced on some sites by the principal cereals of the Fertile Crescent, barley and wheat. There has been much interest in the chronology and consequences of the meeting of east and west staple crops in prehistory (1820). Here, its notable consequence was to facilitate the sustained settlement of the Tibetan Plateau’s higher altitudes. The importation of wheat and barley enabled human communities to adapt to the harsher conditions of higher altitudes in the Tibetan Plateau, a possibility raised in previous studies (1521).

The key addition was barley. During phase three, from around 3600 cal yr B.P., sites can be divided into those that lie above or below 2500 masl. In the lower-altitude group, the longstanding crops, broomcorn and foxtail millet, are joined by barley as a third component in an otherwise traditional dietary repertoire. In the higher-altitude group, however, the frost-sensitive millet is absent, and the cold-tolerant barley has moved to a primary position (Fig. 2D). Alongside the presence of wheat (also relatively cold-tolerant) and sheep, the diet at these high altitudes has clearly been transformed, but in a manner that enabled sustained settlement at unprecedented altitudes.

There’s been a lot of interesting work on the genetics of Tibetans recently, from altitude adaptation from archaics, to the inference that a great deal of Tibetan ancestry is actually shared with the Han and other lowland groups in the past three to four thousand years. These results make more sense if you realize that the arrival of more advanced agricultural techniques reshaped the possibilities of habitation for humans at higher densities. In fact, it is almost certainly no coincidence that it is during the period of agriculture that the great fusions between the disparate “branches” of the human family tree came back together; higher population densities across huge areas mean that de facto gene flow no go zones disappeared.

Open Thread, 1/18/2015

51Jb17R6p6L._SY344_BO1,204,203,200_Currently reading Adrian Goldsworthy’s The Fall of Carthage: The Punic Wars 265-146BC. A read his How Rome Fell: Death of a Superpower years ago, so no surprises. He’s a military historian, so battles, down to the alignment of maniples and details of logistics, operate in the foreground. Not normally my cup of tea, but a nice change up from the focus on social history which seems to be more common today in these sorts of treatments. I also have some Anthony Evrett biographies on deck, but I think I’ll probably hit Ian Morris’ War! What Is It Good For?: Conflict and the Progress of Civilization from Primates to Robots first. It’s the sort of “big history” which is a better complement to the sort of narrative history that Goldsworthy seems adept at writing.

So you want to be a population geneticist/genomicist?

hartleA friend of mine is beginning grad school and has settled upon a lab. The core research within the laboratory is population genomics, and they now need to get up to speed in the area. Taking a class is certainly the start. You can read Haldane’s Sieve to keep up on the literature, which is a necessity if you are doing genomics work, as texts get out of date quickly. Additionally, Graham Coop, Joe Felsenstein and Kent Holsinger have excellent online notes. The upside to this is that they are free. The downside is sometimes you are away from a computer screen. Often a soft intro recommended by many is John Gillespie’s Population Genetics: A Concise Guide, which nicely has a Kindle edition. But if you are going to do graduate level work, I think it is best to just go whole hog. The Gillespie book is appropriate for a quick course or for the undergraduate level, but you really need something as a reference at some point. And for that nothing beats Daniel Hartl and Andrew Clark’s Principles of Population Genetics. There are other texts out there in this area. For example, I have Philip Hedrick’s Genetics of Populations, and Alan Templeton’s Population Genetics and Microevolutionary Theory. For various reasons I would still pick Hartl & Clark if I had to pick.

falconerI also think it’s important to know quantitative genetics, and for that Trudy MacKay and Douglas Falconer’s Introduction to Quantitative Genetics is the best bet in the business that I know of. It’s an excellent complement to Principles of Population Genetics because it starts with pop gen foundations. Derek Roff’s Evolutionary Quantitative Genetics and Michael Lynch and Bruce Walsh’s Genetics and Analysis of Quantitative Traits are probably too specialized for the beginner, and frankly even many stepped in the field haven’t read those books.

slatkinnielsenThere are plenty of other books out there of elements. In my previous post I mentioned Elements of Evolutionary Genetics. The old John Maynard Smith classic Evolutionary Genetics is also excellent. But if you are working in genomics and want a book less focused on classical methods and geared toward contemporary best practices, then Rasmus Nielsen and Monty Slatkin’s An Introduction to Population Genetics: Theory and Applications is pretty good. It’s a short book, and because it’s in its first edition there are many errors in it. From what I recall it was developed out of notes from a course taught at Berkeley, and it outlines the sort of methods you see in the papers which being published today, utilizing coalescent theory and site frequency spectra. It might be a reasonable quickstart, though I’m not sure it is developed well enough to be a reference.

Machinery & the mine, quantitative genetics & genomics

elementarysofevolutionarygeneticsIn the early 1970s the eminent evolutionary geneticist Richard C. Lewontin wrote that population genetics “was like a complex and exquisite machine, designed to process a raw material that no one had succeeded in mining.” By this, Lewontin meant that in the 1930s when R. A. Fisher, Sewall Right and J. B. S. Haldane established the theoretical foundations of the field, the techniques to discover the variation in populations to test their suppositions was rather thin (naturally, this resulted in many controversies, see The Origins of Theoretical Population Genetics). Geneticists were using classical methods, utilizing salient phenotypes which were proxies for underlying genetic markers, and tracing patterns of co-inheritance of traits with known locations in the genetic map with novel mutants. Researchers were not even clear at that point as to the underlying biochemical structure of the particle of Mendelian inheritance, what we term DNA. That arrived onto the scene in in the 1960s. But in the early 1970s when the above was written we’re not talking about DNA sequencing. Rather, this is the allozyme era, which Lewontin helped usher in with a paper in 1966. He expresses the excitement of the times later in the passage:

Quite suddenly the situation has changed. The mother-lode has been tapped and facts in profusion have been poured into the hoppers of this theory machine. And from the other end has issued–nothing. It is not that the machine does not work, for a great clashing of gears is clearly audible, if not deafening, but it somehow cannot transform into a finished product the great volume of raw material that has been provided.”

Despite the pessimism expressed above the emergence of molecular evolution stimulated the debates around neutral theory. Over a generation ago evolutionary geneticists were grappling with the swell of data which was confronting theoretical frameworks constructed in the early 20th century. Today we live in the “post-genomic” era, and now think in terms of whole genomes. The details may differ, but many of Lewontin’s observations in the 1970s still hold true, as novel results meet the paradigms of old. Last month in PNAS Brian Charlesworth published a paper which brought this to mind, Causes of natural variation in fitness: Evidence from studies of Drosophila populations. You may know Charlesworth as the coauthor of Elements of Evolutionary Genetics, an encyclopedia of a text which I highly recommend to all. In the paper, which is both review for those of us not steeped in Drosophila genetics, and a distillation of derivations to be found in the supplements, Charlesworth notes that there is a contradiction in terms of the typical selection coefficients inferred for deleterious alleles from population genomics in relation to those from quantitative genetics. Population genomics is a new field, and involves sequencing many markers (often whole genomes) to good accuracy across a reasonable number of individuals. Quantitative genetics is a more classical framework utilizing statistical methods which interpret variation in traits within laboratory populations.

220px-Drosophila_repleta_lateralThe fruit fly has a storied role in Mendelian genetics. To a great extent the study of the fruit fly is the early history of Mendelian genetics (see Lords of the Fly: Drosophila Genetics and the Experimental Life). Therefore it is natural that a large body of research exists in this area, and one can’t accept novel results obtained through new methods such as genomics at face value without some degree of skepticism. Charlesworth notes that the extremely small fitness effects of the mutation discovered via genomic methods are biased toward single nucleotide variants (SNVs); point mutations. In contrast it seems likely that the larger effect mutations implied by quantitative genetic studies, which are rather rare, and so missed in population genomic sample sizes, are due to transposable elements (TEs) interspersing themselves across the genome, and presumably disrupting function. In line with older theoretical models, most of the variation in fitness is due to a small number of mutations. Presumably as genomic methods get better (e.g., longer read to catch repeat elements and larger sample sizes) they will converge upon the older established quantitative genetic methods. Two interesting other results in this paper is that much of the variation is due to balancing selection. For theoretical reasons balancing selection can not be pervasive across the genome (too much fitness variation would result in huge death rates per generation), but, of the variation within the population much of it is maintained by balancing selection according to Charlesworth. Another interesting dynamic is that the population genomic method seem to be better at capturing the distribution of fitness effects in humans, because of our smaller effective population size. You can read the paper for the technical reason why, but the key here is to remember that one has to be careful about extrapolating from model organisms. The models are imperfect, and we always need to never outrun our ability to generalize.

As genomics becomes pervasive in population genetics this sort of analysis will be more common. Rather than “genome-of-the-week” papers we’ll move to actually trying to grapple with what the sequence data is telling us specifically about the lineage in question, and, what we can generalize from the results about evolution writ large. Some organisms have a long history of scientific study, so population genomics will supplement and complement. In other cases though organisms do not have such a rich literature and scientific culture, and the pitfalls that are highlighted here might alert us to the deficiencies in genomic methods.

Citation: Charlesworth, Brian. “Causes of natural variation in fitness: Evidence from studies of Drosophila populations.” Proceedings of the National Academy of Sciences (2015): 201423275.

80% of public support mandatory labelling of food containing DNA

dna

The title comes from a result in a survey commissioned by the department of agricultural economics at Oklahoma State. I’ve highlighted the response in the context of others. The issue here is that about the same proportion of the public also supports mandatory labelling of “genetically modified organisms” (GMO). This issue can be parsed in numerous ways, but one common tack, even accepted by many scientists who reject the fear of GMO is that the public has a right to know what is in its food as a matter of principle. But what if we put the proposition forward that the public has the right to know what quantity of DNA was in its food? I think perhaps many who make the argument that the public have the “right to know” might acknowledge that this is not an absolute right, and that there isn’t something in our “Natural Rights” that includes food labelling.

A major problem when addressing GMO is that many people deny that GMO is the issue at the heart of the debate. Rather, they suggest that the public has the “right to know.” Or, the problem is agribusiness. And so far. But from what I have seen and heard much of this is an artful dodge. The reality is that GMO makes people uncomfortable, and that discomfort is to a great extent not predicated on a rational basis. Therefore they appeal to other avenues of objection which can give their intuition a solid basis of argumentation.

Human sex differences exhibit context dependence

Sex ratio effects on reproductive strategies in humans:

Characterizations of coy females and ardent males are rooted in models of sexual selection that are increasingly outdated. Evolutionary feedbacks can strongly influence the sex roles and subsequent patterns of sex differentiated investment in mating effort, with a key component being the adult sex ratio (ASR). Using data from eight Makushi communities of southern Guyana, characterized by varying ASRs contingent on migration, we show that even within a single ethnic group, male mating effort varies in predictable ways with the ASR. At male-biased sex ratios, men’s and women’s investment in mating effort are indistinguishable; only when men are in the minority are they more inclined towards short-term, low investment relationships than women. Our results support the behavioural ecological tenet that reproductive strategies are predictable and contingent on varying situational factors.

The topline result is simple, and takes off on basic evolutionary logic. When there is a surplus of men then they compete to “lock in” women into long term relationships. In contrast, when there is a surplus of women the men tend to be much less inclined to invest in one specific woman. In human ethology and evolution there has long been a debate about “cads” vs. “dads.” Are humans by nature polygynous, or, are they are monogamous? More specifically, is high male investment our “environment of evolutionary adaptedness”? The evidence from cross-cultural comparisons seems to suggest that human social organization and individual strategy is facultative. Or, as an economist would say, humans respond to incentives.

This particular research occurred within one ethnic group in Guyana, but there are many other situations where one could test this thesis. For example, in the military (male surplus) or at historically women’s colleges where men are now admitted (e.g., Vassar). Personal experience suggests that when men are at a deficit caddish behavior is the norm. I have less knowledge of the converse, perhaps because there’s less communication about this between men (i.e., men are less likely to “brag” about locking down one particular woman in a long term committed relationship than they are to advertise the notches on their belt).

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