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 importance, such as education, as well as biological parameters, such as brain size. Additionally, the effect size of genetic variants associated with general intelligence are likely to be very small. This means that you should be immediately skeptical of claims that a common variant segregating 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. What set of issues do you think the Republican party would shut the government down over?

* 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. Unsurprisingly 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 he was their great antagonist. 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 antique 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, even by a general as creative and competent as Hannibal. The Hellenistic king 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, where only the victors were left standing. In contrast 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, nor 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, whether non-Latin Italian or Greek). And, the citizen base of Rome was notoriously broad, because the Roman system was expansive, assimilating allies and elites of foreign polities 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, Spaniards, and assorted Italian peoples inimical to the Romans (e.g., the Gauls of the Po valley). 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 to complete a broad mission, while its contemporaries purchased smaller professional armies to achieve specific tasks. 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 available to the military are the major 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 obvious to contemporaries. 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 as 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 . The French innovation of the early modern period of conscripting the whole nation for war could only gain them advantages for so long as other Europeans nations did not imitate them. When they did so they ultimately surpassed them in raw quantity, and emerged victorious.

warandpeaceandwarThe 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. Rome rose as an idea, and it fell as an idea.

* 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 evolutionarily elegant

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 its 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 as 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. 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


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. I 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.

One thing about The Fall of Carthage (and to some extent the author’s works more generally) that I like is that it dispels some of the preconceptions we have about pre-modern hand to hand conflict. In particular, a lot of our mental image is what Goldsworthy would term “cinematic.” The reality is that a lot of the pitched battles were very tentative, and full action probably occurred for less than 15 minutes, even if extended hostilities could go on for as long as hours.

Update: I don’t link to other blogs much, partly because I don’t have much time to read them with my other obligations, but Pseudoerasmus runs a shop with very high intellectual quality. Recommended. In a similar vein, Scholars Gate.

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 steeped in the field haven’t read those books.

slatkinnielsenThere are plenty of other books out there which might suffice in some fashion. 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 (for what it’s worth, I have a copy of it too, and it is being used in graduate level courses here at UC Davis).