Open Thread, 5/31/2015

51eKPU7v6WL._SX258_BO1,204,203,200_Recently a prominent public intellectual emailed me and asked for an introductory genetics text. Not necessarily focused on population genetics (in which case, John Gillespie’s Population Genetics would do). I suggested An Introduction to Genetic Analysis, mostly because it seems pretty comprehensive, and, runs the gamut from classical genetic analysis to 21st century genomics. Yet I have to admit that I did not take an introductory genetics class as an undergraduate. My degrees are in biochemistry, and biology. But, I added the second major later, and basically bluffed my way into taking upper division genetics courses only.* An Introduction to Genetic Analysis is what I studied for my qualifying exam, so I’m familiar with it. But does anyone have other suggestions? E.g., has anyone tried out From Genes to Genomes?

41rxx-UtsWL._SY344_BO1,204,203,200_In other genetics-related news, I’m going to be involved in a workshop on genetically modified organisms for the next few days. Though I don’t talk about it much, I’m a big proponent of GMO. If you want a perspective that will perhaps alter your preconceptions, Pam Ronald’s Tomorrow’s Table: Organic Farming, Genetics, and the Future of Food is a good introduction. Basically, my position is that the anti-GMO position is large part a luxury consumption good. In a world of horizontal gene transfer (our own human genomes seem to be about ~5% virus) GMO is not ipso facto concerning. Rather, what many people worry about really has nothing fundamentally to do with GMO, but with excessive centralization and corporate food production monoculture. But the key to recall here is that there is nothing fundamental in the connection between GMO and corporate agriculture. The corporatization of “organic” illustrates this. This segment of food production has higher profit margins, and so naturally corporations have become big proponents of it. Finally, some of you may have read Nassim Nicholas Taleb’s The Precautionary Principle (with Application to the Genetic Modification of Organisms). One thing I will say is that obviously I don’t buy the thesis in this case, but listening to him being interviewed by Russ Roberts, it is also pretty obvious he’s not a biological scientist because he makes some obvious factual errors in characterizing the scientific consensus. This doesn’t invalidate his position obviously, but it gets a little tiresome throughout the podcast when he argues that biologists themselves are not in a position to do appropriate risk assessment in relation to GMO (this is a defensible position in my opinion, insofar as it takes a diversified skill set which many biologists and non-biologists do not have).

OrientalismSo I’m reading Edward Said’s Orientalism. Mostly it’s so I can better mimic and mock the sort of postcolonial and critical race theory bot that you see on the interwebs. I think I do a pretty good job as it is, but perhaps I’ll try and pull an Alan Sokal at some point in the future, though this time going on about how genetics is fundamentally a tool of white racial oppression or something like that. Unfortunately this sort of “discourse” is actually very common in universities, and is starting to seep through into non-humanities degree programs through general education requirements. Because it’s a fad it will probably pass, but for a few years we’ll hear a lot about how things are “problematic” and “privileged.” Speaking of Orientalism, one of my major issues with Said’s work is that it was so loosely connected to facts, and also had obvious historical errors. But this is not a major issue for most purveyors of postcolonial theory, who basically seem to believe that excessive adherence to “fact” is a tool of oppression (implicitly, if not explicitly, as you can’t let facts get in the way of a good Theory).

I’ll end by pointing out a comment thread below which is what I’d like to see more of. It’s between Troy and Tobus for the most part (Ray also gets involved). I’m actually not very interested in what they’re discussing, but the individuals are engaging at a high, and civil, level. It strikes me as a genuinely edifying discussion which will show up in search engine hits for years to come. Bravo! (the thread begins with fits and starts here)

* Yes, I did take a very introductory genetics module as a biology major, but it lasted all of four weeks.

Modern genetic variation is poor representation of past genetic variation

Seven-DaughtersThere’s a new open access paper in AJHG, Tracing the Route of Modern Humans out of Africa by Using 225 Human Genome Sequences from Ethiopians and Egyptians, which is nice in that it uses state-of-the-art methods to analyze the genetics of a part of the world that warrants greater investigation. As the title of the paper implies the authors are focusing on a region which is likely the site of the exit of an ancient African population ~50-100,000 years ago which is responsible for over 90 percent of the ancestry of non-Africans. In short, they’re looking at the variation of modern populations across the region, and relating it to populations outside of the region, to infer historical relationships. This method has a long pedigree, at least by the standards of historical population genetics. About 15 years ago the Oxford geneticist Bryan Sykes wrote Seven Daughters of Eve, where he traced ancient European migrations to the most common mtDNA haplogroups in the continent. Using these results Sykes asserted that most of the ancestry of modern Europeans derives from Paleolithic hunter-gatherers; not Middle Eastern farmers. More precisely, modern Europeans exhibit overwhelming continuity with the Pleistocene populations. It turns out that this is wrong.

We know this because of ancient DNA, which is coming to various novel conclusions and overturning older understandings. One of them is that the genetic variation you see in a locale today has limited time depth into the past. That is why I state that it is likely that Cro-Magnons may contribute to less than 1 percent of the ancestry of modern Europeans. There are regions, such as the New World, where over the past 10,000 years genetic turnover on the whole has been modest, to negligible (most of the Holocene turnover in the New World before the arrival of Europeans is in northern North America). But this seems the exception rather than the rule. In South Asia, Africa, Europe, Siberia, East Asia and Southeast Asia, there is no dispute that the Holocene witnessed enormous changes in the genetic and demographic makeup of the dominant population. The flip side is that very ancient “archaic” lineages in some regions of the Eurasia have modern descendants. That is why I say we need to update our priors; the ancient branches of our family were mostly, but not entirely pruned, while many of the recent branches were mostly or even entirely pruned.

This brings me to the main question: how plausible it is that the genetic patterns on evidence in the paper in AJHG tell us about human evolutionary history with time depths of ~50,000 years. Color me skeptical. There are some specific issues that I’m confused by, in addition to the bigger framework. Greg Cochran has already put them into focus rather trenchantly. First, this section of the paper:

Using ADMIXTURE and principal-component analysis (PCA)18 (Figure 1A), we estimated the average proportion of non-African ancestry in the Egyptians to be 80% and dated the midpoint of the admixture event by using ALDER to around 750 years ago (Table S2), consistent with the Islamic expansion and dates reported previously.

300px-Fayum-34A plain reading implies that 750 years ago non-African ancestry admixed into the population of Egypt so that it’s now 80% of the ancestry. Obviously this is insane. Egypt has a long history, and all the evidence that is not genetic indicates that ancient Egyptians were predominantly a population with Near Eastern and North African, not Sub-Saharan, affinities. The Roman era Fayum portraits suggest a people who resemble by and large modern Egyptians. Some do seem to have aspects of appearance which strike one as Sub-Saharan, but the presence of Nubians, as well as likely an ancient admixture event that occurred when Middle Eastern farmers arrived in the Nile Valley, can explain that. But when ascertaining the “Out of Africa” event you need to focus on the oldest element of ancestry. So you would have to look the people who contributed indigenous African ancestry well before the emergence of Egypt as a distinct civilization.

Here is the confusing part which inverts expectations. This last component is most likely to be within the “Non-African” segments of the Egyptian genome. I say this because the latest period of a mass population movement into Egypt from the Near East is ~8,000 year ago. 8,000 years is a long time, so recombination every generation would break apart the association between tracts of ancestry traceable to the newcomers, and that traceable to indigenous hunter-gatherers. Over time a new synthetic populatoin with its own distinctive population profile emerges. This is the case with South Asians, who are genetic compound of two very distinctive groups with extremely diverged histories. The latest evidence suggests that the admixture occurred on the order of ~4,000 years ago. That’s half the time depth of what likely occurred in ancient Egypt.

61kCcH+1C9L._SY344_BO1,204,203,200_And about the African ancestry they did focus on, the 750 year time depth gives you a clue about where it came from: the rise of the Islamic empires and trans-Saharan trade enabled by camel triggered a massive influx of slaves from Africa into North Africa and the Near East (there was also an influx of slaves from the Caucasus and Central Asia, and for a time Europe, in large part because Islamic law banned the enslavement of believers). In the Maghreb these slaves were from West Africa. In the Persian Gulf the sources were diverse, but many were from East Africa. The natural source of Egyptian slaves is likely to be from the Sudan, what was ancient Nubia. Also, the Gumuz, who are used as a relatively unadmixed Ethiopian population (i.e., low Eurasian admixture fraction), are themselves of possible Sudanic origin and background!

I can agree that the Nubian/Sudanic ancestry exhibits a closer relationship to the population basal to non-Africans than West Africans. But, to me this paper does not make a strong case for a “northern” route through Egypt compared to the “southern” route, via the Bab-el-Mandeb. First, 50,000 years is a long time. My null assumption is that there has been enough population movement in Northeast Africa even before the Holocene to obscure the signal. Second, even without this consideration in mind, it strikes me that the African ancestry in Egyptians that they are focusing on is not a good geographic proxy in the first place, since it derives from Sudanic groups from further south. Finally, I do observe that this region of the world is relatively dry, making ancient DNA a possibility. So I have optimism that greater clarity will be achieved in the near future.

The Religious Right’s Blank Slate Fallacy & The Duggars

Crime rates from FBI, % "No Religion" from General Social Survey
Crime rates from FBI, % “No Religion” from General Social Survey

The_Blank_SlateIt’s easy to point out the cultural Left’s adherence to all sorts of social constructionisms. My post Men Are Stronger Than Women (On Average) has a lot of Google juice because it now gets cited online a fair amount in arguments…because people are obviously taking the converse position (not that women are stronger, but that the difference is not major). But, there’s a fair amount of ignorance and flight from reality to go around. Probably the biggest blind spot on the cultural Right in the United States is the “family values” Uber Alles stance. As documented over 15 years ago in The Nurture Assumption shared family environment, basically your parents’ non-genetic influence, is relatively minor in affecting behavioral life outcomes (this is not to say that the issues aren’t subtle, but a simple projection from family home to individual outcomes is not viable).

But there’s another major confusion when it comes to the religious Right in particular, and that concerns the origins of morality and ethics. Most people are probably aware of the Josh Duggar fiasco at this point. If you aren’t, Google it. There isn’t much to say that hasn’t been said, but this post from his father-in-law has been raising eyebrows:

…It is a mercy of God that he restrains the evil of mankind otherwise we would have destroyed ourselves long ago. Many times it is simply lack of opportunity or fear of consequences that keep us from falling into grievous sin even though our fallen hearts would love to indulge the flesh. We should not be shocked that this occurred in the Duggar’s home, we should rather be thankful to God if we have been spared such, and pray that he would keep us and our children from falling.

This attitude is entirely unsurprising to me, I’ve heard it many times from evangelical Christians. The theory is that without religion, and particularly their religion, they would be “a rapin’ and murderin'”. Why? Because that’s what people do without God. Believe it or not, I have never believed in God, nor have I raped and murdered (or molested). Nor do I think that raping and murdering would be enjoyable. Nor do I think that the evangelical Christians who proudly declaim that without their savior they would rape or murder with abandon would actually rape or murder.

This idea that without religion there is no morality is very widespread in the subculture, to the point of being an implicit background assumption that informs reactions to many events in concert with the idea of original sin and fundamental human depravity (thank you St. Augustine and John Calvin!). I have a socially liberal friend from an evangelical background, who is still somewhat associated with that movement, who confided in me that to did look forward to debauchery in a post-Christian life on some occasions. I had to convince him that even if he was not religious life was not likely to change much for him in the sex department unless he shifted his standards somewhat. Without God all things are not possible, believe it or not.

Religion_Explained_by_Pascal_Boyer_book_coverThe fundamental misunderstanding here is actually one of intellectual history. Many evangelical Protestants in particular envisage the world before the revelation of God to Abraham, but sometime after the Fall, as a Hobbesian one of “all-against-all.” This is not limited to evangelical Christians. Many Muslims also conceive of the pre-Islamic jahiliyya in Arabia as one of pagan darkness and debauchery. The root misunderstanding is conceiving of morality and ethics as a historical human invention, as opposed to formalizations of deep cognitive intuitions and social-cultural adaptations. Broadly, I agree with Peter Turchin that the origin of modern organized religions has its ultimate roots in the social and institutional needs of pan-ethnic imperial systems during the Axial Age. The synthesis of a supernatural Weltanschauung with the nascent enterprise of philosophy and the older intuitions of tribalism allowed for the emergence of the multi-textured phenomenon which we now term organized religion. Religion co-opted and promoted morality, but it did not invent it. The Israelites put in their Lord God’s mouth their own morality that was existent before his invention! Prior to the development of organized religion it seems likely that the connection between supernatural agency and morality was more tenuous and conditional (and even then, the angry and jealous petulant Yahweh of the Hebrew Bible has plenty of glimmers of the amoral gods of yore).

That is why even with the diminishing of organized religion in the modern West there has not been a correlated rise in crimes such as murder. The connection between ethical monotheism and ethics is not nearly as necessary as the religious would have you believe. The chart at the top does not prove at all that irreligion leads to decrease in crime (on the contrary, there is modest evidence that religious involvement results in mild prosocial tendencies when you control for confounds). But, it does show starkly that over the last 25 years in the United States there has been a simultaneous decrease in violent crime, and, a massive wave of secularization. This contradicts a model which proposes that religion and ethical behavior are necessarily and deterministically associated.

So no, in the case of Josh Duggar it isn’t a matter of “there, but for the grace of God, go I.” I’ll let others psychoanalyze his behavior, but it isn’t a normal human impulse which has to be constrained by the teachings of religion. If religion has to teach you not to molest your sisters you’ve got a problem, son! And it has nothing to do with your soul. This may be a boundary condition which validates the “nurture assumption.”

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Grafts along the human bramble

Citation: Racimo, Fernando, et al. "Evidence for archaic adaptive introgression in humans." Nature Reviews Genetics 16.6 (2015): 359-371.
Citation: Racimo, Fernando, et al. “Evidence for archaic adaptive introgression in humans.” Nature Reviews Genetics 16.6 (2015): 359-371.
41ePHetk1dL._SY344_BO1,204,203,200_Nature published a paper recently, New species from Ethiopia further expands Middle Pliocene hominin diversity, which seems to complicate the deep history of the hominin lineage. More precisely, it gets curiouser and curiouser, as the number of human(ish) groups proliferates. Honestly I don’t know well this will hold up, a lot of science seems to fade out. Remember the article in Science, A New Kind of Ancestor: Ardipithecus Unveiled? I’m not totally clear on whether the controversy about this find has resolved. At least we’re at the stage where most people seem to accept that Homo floresiensis was a true hominin lineage, rather than a pathology. (by the way, Carl Zimmer has a good write up on the most recent addition to the human family tree)

Genes are something that is more concrete to me. Nature Reviews Genetics has two pieces of interest in this domain. First, Evidence for archaic adaptive introgression in humans. A close reader of this weblog will find little of surprise; the authors do an excellent job of reducing down the key results of the past five years or so that have issued from the discovery that the ancient whole genome of the Neandertal bears all the hallmarks of having been carried over into some lineages of modern humans. In particular, the authors focus on adaptive alleles and regions through a statistical genomic lens. Second, Svante Paabo has a comment in the same edition, The diverse origins of the human gene pool (ungated), which leans heavily on the previous piece.

51r8Ph-vcaL._SY344_BO1,204,203,200_Paabo to me seems to finally put to bed some old conflicts which have been roiling the field of paleoanthropogy for decades. I think we’re going to finally see the abating of the rhetorical war between those who promote “Out of Africa” vs. “Multi-regionalism.” The fact is in some ways both viewpoints are worth taking into account. As Paabo, and others, have noted, the former model turns out to likely be correct about the provenance of most recent human ancestry. It is mostly derived from an African or near-to-African (e.g., in the Middle East) population on the time scale of ~100,000 years. But, the latter model’s emphasis on regional evolution and adaptation and gene flow across a meta-population system is also a critical insight in understanding the dynamics of how modern humans came to be.

I do like the fact that Paabo also seems to moving past the idea that genomics will yield the one allele or set of alleles that define what made modern humans so biologically special. I don’t have an opposition to biology as being determinative in our cultural flexibility. But, if anything has been clear in what genomics is telling us about recent human evolutionary history, it’s that it is rather more complicated than we might have imagined. I doubt the uniqueness of the surviving lineage of hominins is going to be any more, or less, subtle in the difficulties of resolution.

I do have one bone to pick with Paabo. He states that:

Adaptation through the acquisition of new mutations is generally a slow process: it is rare for favourable alleles to appear, and these are often lost by chance when they first occur in a single individual or in very few individuals. By contrast, if favourable alleles have emerged in one group, they can spread to other groups relatively rapidly by gene flow. This process, called ‘adaptive introgression’, is well documented in bacteria and plants, and described in some cases in animals but it has not previously been considered an important factor in human adaptation.

The idea of “adaptive introgession” has been something I’ve been thinking about, and talking about, in relation to human evolution since 2006 (Google it). That’s because of the focus that Greg Cochran, Henry Harpending, and John Hawks, put on the topic (all these years later I am also professionally interested in this topic, but that’s for a later post!). Now, it is true that Svante Paabo does not seem to have thought of the issue in much detail. His book Neanderthal Man has no references to “adaptive introgression” according to Google Books. In contrast, 10,000 Year Explosion has 9 mentions of the term.

introgressI will note that the authors of the review paper that Paabo leans on heavily for his comment don’t make this omission where credit is due. They cite both Greg Cochran and John Hawks, with a special laudatory note.

Finally, I want to suggest that to a great extent, Multi-regionalists excepted, the previous consensus in human evolutionary studies tended to overestimate the extinction rate of “archaic” lineages. But, it also underestimated the extinction rate of modern lineages. That is, archaic lineages rooted outside of Africa before ~100,000 years ago may play more of a role in the evolution of our modern lineage than we may have guessed when it comes to both genotype and phenotype. Paabo quotes the standard figures of a few percent for Neandertal ancestry, and ~5 percent of Denisovan among Oceanians. From all I have heard and know this seems about right, but I do wonder if this is actually just a floor. Without ancient genomes I suspect we’d still be debating the possibility of archaic admixture from inferences which only statistical genomicists would have a good grasp of. In 2006 Jeff Wall and Michael Hammer stated that “Neanderthals and an as yet unidentified archaic African population contributed to at least 5% of the modern European and West African gene pools.” They were basically dead right. Second, the ancient DNA is also yielding the conclusion that many local populations which flourished during the Pleistocene outside of Africa seem not have to left much genetic legacy today in the same regions. We’ll get more clarity on the topology of the human phylogeny in the near future, but it strikes me that it’ll exhibit features which are somewhat at variance with what we’d have expected 10 years ago.

Blue Sky and Brown Earth: look to the Red Planet!


41gl5ENbKZL._SY344_BO1,204,203,200_Today on Medium I saw a post, Shouldn’t We Fix Poverty Before Migrating to Mars? The substance of the piece is less important to me than the title, because the title expresses a viewpoint common among many. Why look to the heavens when we don’t have heaven here on earth? The first time I heard this sentiment was as a child when I saw Joe Kennedy II express this opinion on the floor of congress in relation to funding to NASA in the 1980s. As something of a space-nerd the sentiment shocked me to my core. Obviously I understood poverty in at least a sensory fashion. I was born in Bangladesh before it was a textile powerhouse and there wasn’t at least the promise of development. But as a nerd it seemed to me that sacrificing knowledge of the world for a full stomach seemed like a false trade-off. Of course I was self-interested. This is what I wanted to be true.

But as it happens, I do believe that it is the truth, and that is because what we know from economic history. The rise of the post-Malthusian consumer economy validates the position that we should have one eye to the heavens above, and another focused on the concerns of the earth. The two are synergistic. What is needed for prosperity in a manner we understand to be prosperity in our day and age are two things. First, increased economic growth through gains in productivity. Second, a lack of concomitant population growth to eat up the gains in productivity. The demographic transition. In other words, get smarter to get wealthier, and don’t divide that wealth between too many children.

410uvoV1qDL._SY344_BO1,204,203,200_The West, and more precisely Britain, was the first society to break out of the “Malthusian trap,” whereby gains in productivity were eaten up by population growth. This change was not foreseen by the economists of the day. Thinkers such as David Ricardo and Thomas Malthus assumed that the “end of history” was always characterized by a stationary state where population and economic production balanced out so that much of humanity was caught in a condition of immiseration. The irony is that they were flourishing just during the period that Britain was breaking the iron laws of economics as they were understood at the time. What we term the industrial revolution was triggering the rise in gains of wages to unskilled workers that would continue to 1970, and the demographic transition would lead to the emergence of the two-child nuclear family. There are many books which chronicles this change, but one is particularly good for a lay audience is David Warsh’s Knowledge and the Wealth of Nations: A Story of Economic Discovery. It traces the evolution of endogenous growth theory, basically a model which accounts for economic growth by parameters such as innovation and human capital (this problem is not solved by the way). Greg Clark’s A Farewell to Alms and Kenneth Pomeranz’s The Great Divergence as two alternative takes forwarding specific more empirical theses.

41W-0XB-m2L._SY344_BO1,204,203,200_But let’s think about this in a more high level manner. Compare the Chinese intellectual and political tradition and that of the West. Since the Axial Age there are broad similarities, particularly with the rise of humanistic traditions. But to generalize one might assert that the Chinese tradition has been more pragmatic and concrete, while the Western tradition has allowed for more abstract concepts and considerations. The most otherworldly element of traditional Chinese thought actually turns out to be exogenous, that of Buddhism (the rise of Buddhism coincides with the decline of scientific Daoism and the rise of religious Daoism). After the Tang dynasty Buddhism lost its place at the table of Chinese elites, and the dominant ethos was that of Confucianism, which prioritized proper governance on earth to maintain harmony and order. A key consequence of this was that scholar-officials were fixated on the need for the peasantry, the true productive units of society, to be prosperous and fruitful. The Chinese system was deeply humanistic and civilian in its orientation. It can be argued that the Chinese state and society by the 18th century had reached the stationary state at the “end of history.” Every unit of production was being squeezed that could be squeezed by traditional means agriculture and trade between regions to maximize comparative advantage. They were at the end of the line of economic growth as could be conceived by Adam Smith’s model.

In contrast the West has been subject to less cultural continuity, and was more fragmented. The medieval scholastics, and men such as Baruch Spinoza, reflected a fixation on deep abstraction and a concern with ontology which was marginalized early on in the mainstream of Chinese intellectual thought. Arguably this flight from the pragmatic can be traced back to Pythagoras and the pre-Socratics. Mathematical mysticism continued in Western civilization because of the influence of Plato. Empirical science had its origins with the interests of Aristotle. The fusion of mathematical formalism and empirical methodology in the early modern era wrought a miracle: science. Over time science was turned into the handmaid of technology, and the elixir of innovation emerged from the synthesis.

20130601_FBC699I assume most people can understand how this ties back to the piece in Medium, and the concern of people about poverty now, rather than future dreams and horizons. But we also have to remember that it is a fact that global poverty is declining. China is a big reason, and the root is not the revival of Confucianism,* but the expansion of technological civilization. The production of iPhones is driving the decline in misery, not redistribution or primary production through agriculture. We already have a map to abolish material misery: growth and demographic transition. It may happen in our age that extreme material want will be a memory, just as slavery is.

SaganPaleBlueDotWhat drives growth? Innovation. How do we get innovation? By investing in crazy projects whose payoffs we can’t calculate rationally and whose outcomes are not foreseeable. The reality is that Chinese civilization over ~2,000 years was caught in a local optimum of maximizing prosperity in Malthusian conditions. The Chinese sages were wise, but their eyes only saw to the edge of the horizon. The West’s intellectual forebears were less practical, but more diversified. This allowed for it to break out of the trap of fixating on the practical-before-our-nose. Rather, Western thinkers should dream delusional visions of abstraction and imagination. Worlds beyond imagining for the common ken. When you explore more of the parameter space you are likely to find novel optima which you would otherwise never have arrived upon. To some extent this is how evolution may work, with mutation, drift and co-evolution perturbing cozy fitness peaks. More plainly, we can only realize true innovation when we are able to understand that that entails blue sky long-shots into the deep. That is just the empirical and factual trend over the course of history, not a mystical vision.

But these issue are not simply nakedly utilitarian, they’re also normative. If we crush the spirit to explore and unleash a touch of insanity, even in the face of misery, we crush the human spirit. We were the crazy apes who dreamed to cross the vast blue oceans. Only our ancestors settled Oceania and the New World. We do not stay at home. That is not in our nature. For some of us, to explore is part of who we are. Denying that aspect denies a filament of our being.

Addendum: I have noticed and unfortunate trend of some biologists to denigrate space science as a “waste of money.” That goes to show that even among scientists horizons and wonderment can be constrained by narrowness of vision and zero-sum psychology.

* Confucianism is reviving actually in response to prosperity.

Can a religious person be a good scientist?

Source: Pew

In the culture of science you occasionally run into the sort of person who believes as an apodictic fact that if one is religious one can not by their fact of belief be a good scientist. You encounter this sort of person at all levels of science, and they exhibit a range of variation in terms of the volume of their belief about beliefs of others. I don’t want to exaggerate how much it permeates the culture of science, or at least what I know of it. But, it is a tacit and real thread that runs through the world-views of some individuals. It’s a definite cultural subtext, and one which I don’t encounter often because I’m a rather vanilla atheist. A friend who is now a tenure track faculty in evolutionary biology who happens to be a Christian once told me that his religion came up nearly every day during graduate school! (some of it was hostile, but mostly it was curiosity and incomprehension)

This is on my mind because a very prominent person on genomics Twitter stated yesterday that Francis Collins by the very fact of his evangelical Christianity should not hold the scientific position of authority that he holds (the individual in question was wondering if they could sign a petition to remove him!). The logic was very straightforward: science by its nature conflicts with religion, and those who engage in the sort of cognitive processes which result in religion will be suboptimal in terms of scientific reasoning. As I indicated above the people who promote this viewpoint treat it as a deterministic scientific law. And, importantly there is little reference to cognitive science or survey data to support their propositions. Ten seconds on Google will yield the figure you see above. A substantial proportion of American scientists aver a religious affiliation.

Programming_Perl_4th_Ed_coverMind you, there are patterns. The data when examined in a more granular fashion suggests that academic scientists are more secular than those in industry, as are the more eminent ones. But it doesn’t take much time to think of great scientists who avowed some sort of religious affiliation. In evolutionary biology R. A. Fisher and Theodosius Dobzhansky affiliated as Christians. The mid-20th century evolutionary biologist David Lack was an Anglican convert. In Reconciling Science and Religion the historian of science Peter J. Bowler outlines a movement in early 20th century Britain to accommodate and assimilate the findings of evolutionary biology to that of mainstream Christianity, so it is entirely unsurprising that Anglicans such as Fisher and Lack were active researchers within evolutionary science.

Outside of evolutionary biology there are two examples which stand out in my mind. Larry Wall, the originator of the Perl language which has had a long history in bioinformatics is an evangelical Protestant Christian. And Donald Knuth, the author of the magisterial series The Art of Computer Programming is a Lutheran.

51-C0feX3uL._SY344_BO1,204,203,200_My point in reviewing this data, which should be widely known, is to bring some empiricism to this discussion. What do the data say? Not one’s prejudices and intuitions. One response on Twitter was that empiricism precludes faith. That’s the theory about empiricism. The reality is that there are many great empirical scientists who have a religious faith. Any scientist worth their salt who wishes to air hypotheses about the incompatibility of religion and science on an individual level needs to engage with these facts.

To be fair, I don’t think it’s a coincidence that there’s a correlation in the aggregate between secularism and science. But this issue is complex, emerging at the intersection of cognitive science, sociology, and history. These subtleties can’t be waved away airily with a reference to facts that everyone knows which happens to reflect one’s own personal prejudices. That reminds me of things besides science.

Finally, this truth that in the aggregate scientists are a diverse lot even if there tends to be particular patterns of social concentration is a general one. E.g., most scientists are more liberal than not. But a substantial minority are not, with a fraction of those being rather closeted about this. The average scientist, in particular in the academy, is a secular liberal. But the minority are not trivial. We’re in your lab meetings, at your conferences, collecting data for you, and on your committees, reviewing your grant applications.* Because of the nature of the academy outside of religious colleges there is often silence from this minority lest they be pigeon-holed as out of step with the social culture of science. That’s human nature. And scientists can’t escape that, whether they are in the majority, or the minority. For all the talk of logic and empiricism, scientists are all too human in their basic wiring.

* Much of what I say applies to natural science. From the survey data in the academy non-liberals-to-Leftists are almost entirely absent in sociology and a lesser extent in areas of psychology.

Science, evolved and reimagined

A_Candle_in_the_Dark_by_soraferretScience is a pretty big deal. Science is the foundation for our civilization. Science is the best method we’ve found to map reality, and take us into the unknown on more than whim and prayer. I don’t agree with those who believe that science drained romance from our understanding of the world around us. I don’t agree with those who assert science is just another superstition. I don’t agree with those who assert that science is a tool of oppression by its nature.

With all that stipulated, science has problems. And that’s because it is a human enterprise. Humans are both the root of science’s problems, and, the source of its solutions. Philosophers can think deeply about how science is done, from Karl Popper to Thomas Kuhn, but high level abstraction has little impact on the day to day practice of science. Science today is social. Individuals work in the context of research groups, and then publish and disseminate their findings across the broader community of peers. The social aspect is why genuine scientific productivity on an international scale is so concentrated in a few nations, above and beyond what you might expect from economic development. The per capita gross domestic product difference between Germany and Italy is significant, but it is dwarfed by the yawning scientific productivity chasm between Germany and Italy in any area of science I am personally familiar with. Science exhibits returns to scale. Who you are around makes you smarter in science.

downloadThis is why Twitter has become such a big deal. It’s a way to enable disintermediation; cutting the middlemen and gatekeepers out of the equation, and ratcheting up on the metabolism of discourse so that it is nearly frictionless. About ten years ago some friends of mine disagreed with a scientific paper in PNAS. They were going to write a response, but didn’t think anyone would pay attention, even if PNAS accepted and published it. So they put up a blog post. Today they would probably start responding on Twitter.

This is relevant because of a controversy that recently erupted over disputes about the results of a major paper from a reputable group. Nature has already reported on this, Potential flaws in genomics paper scrutinized on Twitter. Yoav Gilad, a University of Chicago professor, released some critiques of a high-impact PNAS paper from last December, Comparison of the transcriptional landscapes between human and mouse tissues, on Twitter. The critique is now more fully fleshed out in a paper posted at F1000Research. But what has really gotten peoples’ attention is what Mike Snyder, the last author on the mouse-human transcriptional landscape paper, said in response to the way the critiques were delivered:

Michael Snyder, a geneticist at Stanford University in California and co-author of the original paper, stands by his team’s study and its conclusions and says that Gilad broke the “social norms” of science by initially posting the critique on Twitter. Gilad says that he took to social media to highlight his work, which might otherwise have been overlooked.

Obviously there isn’t a book which outlines the social norms of science. These norms have developed and coalesced implicitly, tacitly, over time. And, they change. It’s no surprise that a lot of people on Twitter are taking Gilad’s side in this. Also, many are giving credit to Snyder’s group for releasing the raw data to Gilad for the reanalysis. If Gilad and company are correct then this is another victory for open(ish) data. Derek Lowe has some reasonable thoughts on the details of how this has been playing out in public. I don’t have much to add.*

But, I do wonder how ephemeral the role of Twitter is going to be in the scientific community. After all, Twitter is not a public utility. It’s a public firm which is traded on the stock market and exists to make a profit and return value to its shareholders. There was a time when AOL, or Myspace, were ubiquitous corners of the internet. Though Twitter allows for a level of disintermediation, to some extent it is a stealth intermediary in and of itself.

The social norms of science are evolving, and the rate of change is increasing. I doubt that this generation shall pass into emeritus before the entire edifice of scholarship as we know it, from publishing status quo to the tenure system, is overturned. Snyder put his finger on the fact that Gilad is likely violating the social norms of science, but those were past norms. Scientists are making it up as they go along right now. Genomics in particular, which is a heavily computational field, with many researchers amenable to data sharing, distribution, and reanalysis, is to some extent going to be a guinea pig for other domains. We’re in a time of change, so likely don’t have the clarity we will in a decade or so, when the current maelstrom will have passed and a new equilibrium attained.

* I didn’t pay much attention to the original paper, so I’m having a hard time understanding how the authors didn’t bother to check for batch effects as some are claiming. Finally, I’ve met Mike Snyder, and he’s a very nice person from what I can tell for how big of a deal he is. I hope this resolves without too many hurt feelings and reputations intact on all sides.

Sexual selection as a justification for sex

Citation: Figure adapted from Lumley, Alyson J., et al. “Sexual selection protects against extinction.” Nature (2015).

9780198503361_200Sex is a big deal. William Hamilton spent a significant part of his career on the topic, and the second volume of his collected papers, The Narrow Roads of Gene Land, is focused on this issue. Whenever I talk about sex in an evolutionary biological context one thing that always pops up is why males? In other words, why do so many complex organisms have a whole sex which does not bear offspring? Parthenogenetic lineages of organisms where females can reproduce asexually have double the per generation reproductive output as sexual lineages. And yet over evolutionary history it seems clear that in lineages where sexual and asexual species coexist, the latter are always novel derived lineages. In other words, asexual lineages have a high extinction rate. Sex, and more specifically males, must be good for something. What then?

One hypothesis is that males are good for purging genetic load via sexual selection. On a genetic level all individuals carry deleterious mutations, which they pass on to their offspring. But, because of sample variance in transmission, there will be a distribution of outcomes in any given set of offspring. By chance some individuals will exhibit a higher load of deleterious alleles, while others will carry fewer alleles. If this load is correlated to traits which are visible to the opposite sex, then excess load every generation can be purged through reproductive skew. In other words, one might envisage a situation of sexual selection-mutation balance, where de novo mutations introduced every generation are balanced against deleterious alleles purged from the population through selection of more fit males.

330px-Tribolium_castaneumAll good in theory. But is this empirically true? A new paper in Nature suggests it is. At least for the red flour beetle. The paper is titled Sexual selection protects against extinction. Recall that asexual lineages seem to be more likely to go extinct when one examines them with comparative phylogenetic methods (i.e., with in a clade asexual lineages are invariably young in evolutionary time scales, implying that they do not last long).

41SSqWzJIGL._SY344_BO1,204,203,200_The adapted figure above shows the experimental results which support the proposition that sexual selection purge deleterious alleles. These experiments ran for ~10 years, and consisted of varying primary treatments which differed in terms of intensity of sexual selection in red flour beetles. In panel A you see a comparison between a male and female skewed sex ratios (9:1), red and blue lines respectively. In a male skewed ratio the males are competing for the attention of a few females, and in a female skewed ratio the situation is the reverse. To test for the fitness of the lineages the researchers took the outcomes of long term breeding in these scenarios (fixing the effective population sizes to be comparable) and then forced them to engage in sibling matings. This would “expose” deleterious recessive alleles because of the nature of inbreeding. As is evident above in the female skewed (blue) lineages there is a much quicker extinction rate as inbreeding begins to expose deleterious alleles in the recessive phenotype. In the second set of experiments the authors compared polyandrous (5 males to 1 female) and monogamous lineages. Again, you see that the polyandrous lineages are much more robust to inbreeding, suggesting that sexual selection driving reproductive skew correlated with mutational load is resulting in a lower population wide genetic load.

41czavSUnNL._SY344_BO1,204,203,200_There are many arguments for why sex persists (though many of them do not seem to directly address the cost of males, since sexuality does not necessarily entail two different sexes where one does not bear offspring or produce eggs). I don’t think that sexual selection needs to be the explanation as such. Additionally, I think there is the problem that extremely skewed sex ratios as is the case above does not seem biologically plausible in many organisms. In big and slow breeding organisms, such as humans, extreme sex ratios are not typically common. It seems unlikely that sex is maintained purely through purging of deleterious alleles via a “good genes” model of sexual selection. But then to truly test this hypothesis it strikes me that some sequencing methodologies could be brought to bear. For example, do individuals with lower load have a higher realized reproductive fitness? This is entirely testable.

Citation: Lumley, Alyson J., et al. “Sexual selection protects against extinction.” Nature (2015).

Genetic load is higher outside of Africa


F5.mediumA common model of the range expansion of modern humans out of Africa ~50,000 year ago forces us to conceptualize it is as a tree with successive bifurcations. Each of these bifurcations often is accompanied by a bottleneck in one of the daughter populations, with the sum totality of the demographic events producing a “serial bottleneck” model of the origin of modern human lineages around the world. Though this paradigm has been around in various forms for decades, most influential among geneticists has been the 2005 paper, Support from the relationship of genetic and geographic distance in human populations for a serial founder effect originating in Africa. In the paper the authors show persuasively that heterozygosity declines as a function of distance from Addis Ababa, near the likely point-of-departure out of Africa.

But there’s minor problem with this model. Most extant populations may in fact be compounds of highly diverged late Pleistocene lineages. That is, after an initial serial founder expansion ~50,000 years ago there may have been many local extinctions and admixture events overlaying it. That is the model that Joe Pickrell and David Reich argue for in Towards a new history and geography of human genes informed by ancient DNA. While in a serial founder conceptualization of an out of Africa migration modern populations are the tips of the phylogenetic tree, in the Pickrell and Reich framework they’re syntheses of divergent evolutionary histories. As Towards a new history and geography of human genes informed by ancient DNA shows older genetic techniques and data, not informed by ancient DNA, may not have had the power to differentiate between the serial bottleneck model, and one of reticulation and fusion.

41h+3YmTZRL._SY344_BO1,204,203,200_It seems likely that the serial founder model has some utility. One can still hold defensibly that everyone outside of Africa, excluding recent admixture from within Sub-Saharan Africa, sits within their own phylogenetic clade. That is, all non-Africans are equally related to Sub-Saharan Africans, because all of them descend from an ancient population of ~1,000 breeding individuals. But, you have populations such as South Asians who are both numerous, and, fusions of two very distinct branches of out of Africa humanity. The stylized model of a tree subject to bifurcations fundamentally misleads in this case.

All this came to mind reading a new preprint that’s on biorxiv, Distance from Sub-Saharan Africa Predicts Mutational Load in Diverse Human Genomes. Theory and intuition should suggest to us that out of Africa populations will have higher genetic load of deleterious mutations than within Africa populations. The reasoning is straightforward: the power of selection to remove deleterious mutations is hampered the smaller the effective population size, as random genetic drift becomes more determinative in generation to generation changes in allele frequency. More formally if 4Nes << 1, where Ne is effective population and s is the selection coefficient, then even deleterious alleles behave as if they are neutral. From neutral theory we know that the rate of substitution in this model is simply the rate of mutation. That is, molecular evolution is determined by new mutational input, rather than being constrained or diversified by selection. In small populations which are drift dominated Ne can get very small. I’ve seen assertions that the original group of humans who settled North America and South America may have had an effective population in the first generation on the order of ~100. In their history they also had the out of Africa effective population of ~1,000. In addition, there were likely bottlenecks between Berengia and the out of Africa event.

downloadYou can see in the figure above from the preprint that the number of deleterious mutations does seem to increase with further distance from Africa. Their genomic coverage was good, ~80x on the exome. That is, when they found variants that differed from the reference sequence they could be confident that it was not in error. On the other hand their population coverage struck me as less than ideal, though I am willing to accept that their result is probably true (and obvious with finite resources they selected their individuals and populations to be informative). They admit for example in the text that the Mozabite population has higher heterozygosity due to a back-to-Africa migration, which has had successive admixtures of Sub-Saharan ancestry. In addition, it is also rather inbred. Its demographic history bears no correspondence to the serial founder bottleneck model which spans 50 to 15 thousand years (i.e., from the out of Africa to the settlement of the NewWorld). The Pathan and Cambodian populations also are actually the product of Holocene fusions between distinct groups with very different histories. The PSMC results in the bottom left panel can be thought of as collapsing distinct population histories, and, from what I am to understand may then inflate the effective population trajectories of individuals who descend from admixture events.

As one might expect from this sort of title the authors refer back to the 2005 paper that I mention above. I don’t want to belabor this point, as I think the authors’ results are probably robust, and, important, population history aside. But, much of the audience will not know that the serial founder bottleneck model is now being challenged. The 2005 paper has 588 citations as of this writing. The Pickrell and Reich paper, which was published in 2014, has 5 citations. I just want to mention this since it’s a preprint and presumably the authors are taking in any critiques.

When it comes to burden of deleterious mutations in human populations there have been some conflicting results, reviewed in the preprint, about mutational load. The authors argue that results which suggested that non-Africans did not exhibit higher load were subject to a bias which did not have power to detect non-common variants, and also modeled mutations as additive, as opposed to across the full range of dominance (h). It turns out that non-Africans, and those populations which are more drifted, exhibit higher recessive deleterious loads. This is what you would expect intuitively, as you need large populations to purify this class of deleterious alleles (since they are only exposed to selection in homozygotes). This matters when it comes to expectations of the number of recessive diseases one might expect in populations which practice consanguinity.  I would, though, have liked to see more typical populations in the mix. For example, instead of just African hunter-gatherers it would be nice to see the Yoruba, as well as Han Chinese, and a northern European population. I doubt it would be very surprising, but it would give one a better baseline.

Finally, I want to note that many ancient DNA results, from “archaics” to modern human Mesolithic hunter-gatherer groups, have very low effective population sizes due to inbreeding. Genetic load may be more important in the history of the human species, especially on the edge of the range in the far north, than we may now understand, because of its tendency to reduce fitness of groups due to the drag of recessive disease.

Citation:  Distance from Sub-Saharan Africa Predicts Mutational Load in Diverse Human Genomes, Brenna M. HennLaura R BotigueStephan PeischlIsabelle DupanloupMikhailLipatovBrian K MaplesAlicia R MartinShaila MusharoffHoward Cann,Michael SnyderLaurent ExcoffierJeffrey KiddCarlos D Bustamante, 

Open Thread, 5/24/2015

51QrNyN0KzL._SY344_BO1,204,203,200_In 2002 I read Stanislas Dehaene’s The Number Sense: How the Mind Creates Mathematics. Though it’s not at the same level as Steven Pinker’s The Language Instinct*, it’s not that far below it. There was a time when I read a fair amount of cognitive neuroscience. Not so much now. So I’m finally trying to get through Reading in the Brain: The New Science of How We Read, again, by Stanislas Dehaene. This is partly an exercise of narcissism, since I want to do what I can to understand myself.

CoverReadingInTheBrainSpeaking of which, Bryan Caplan, a big fan of Judith Rich Harris’ The Nurture Assumption, reports that reading is kind of a big deal in developing a child, and impacting their ultimate life outcomes. The effect is modest, but robust. Though also please read Will Ambrosini’s cautionary comments about interpretation of this result.

So what else is going on? I apologize to those whose comments I don’t respond to who are asking me a direct question. Time is finite and it often slips my mind, even though responding to questions is on a “TO-DO”. Also, the new book about Elon Musk, Elon Musk: Tesla, SpaceX, and the Quest for a Fantastic Future, looks interesting. But I doubt the whole of the text is worth purchasing. I care a lot less about Musk’s family background and personal life than I do about his vision for the human race. But really the latter could be outlined on a napkin.

Finally, BAPG XII @Stanford in Palo Alto. May 30th, a Saturday. Looking forward in particular to Michael McLaren’s talk on fitness landscapes.

* The Blank Slate is probably more well known, and Pinker’s most successful book in terms of broad cultural impact. But I think The Language Instinct is his best science book aimed at a general audience.