Modern evolutionary genetics owes its origins to a series of intellectual debates around the turn of the 20th century. Much of this is outlined in Will Provines’ The Origins of Theoretical Population Genetics, though a biography of Francis Galton will do just as well. In short what happened is that during this period there were conflicts between the heirs of Charles Darwin as to the nature of inheritance (an issue Darwin left muddled from what I can tell). On the one side you had a young coterie around William Bateson, the champion of Gregor Mendel’s ideas about discrete and particulate inheritance via the abstraction of genes. Arrayed against them were the acolytes of Charles Darwin’s cousin Francis Galton, led by the mathematician Karl Pearson, and the biologist Walter Weldon. This school of “biometricians” focused on continuous characteristics and Darwinian gradualism, and are arguably the forerunners of quantitative genetics. There is some irony in their espousal of a “Galtonian” view, because Galton was himself not without sympathy for a discrete model of inheritance!
In the end science and truth won out. Young scholars trained in the biometric tradition repeatedly defected to the Mendelian camp (e.g. Charles Davenport). Eventually, R. A. Fisher, one of the founders of modern statistics and evolutionary biology, merged both traditions in his seminal paper The Correlation between Relatives on the Supposition of Mendelian Inheritance. The intuition for why Mendelism does not undermine classical Darwinian theory is simple (granted, some of the original Mendelians did seem to believe that it was a violation!). Many discrete genes of moderate to small effect upon a trait can produce a continuous distribution via the central limit theorem. In fact classical genetic methods often had difficulty perceiving traits with more than half dozen significant loci as anything but quantitative and continuous (consider pigmentation, which we know through genomic methods to vary across populations mostly due to half a dozen segregating genes or so).
Recently I was at the dentist and I was told that because I did not have any caries at this age, I would probably not have to worry about that in the future (in contrast, I do have some issues with gingivitis). I wasn’t surprised that I didn’t have caries, I have no great love of sweet confections. I had chalked up my evasion of this dental ailment to my behavior. To make a long story short my dentist disabused me of the notion that dental pathologies are purely a function of dental hygiene and diet. Rather, he explained that many of these ailments exhibit strong family and ethnic patterns, and are substantially heritable. My mother did suffer from periodontal disease a few years back, and that has made me much more proactive of my own dental health.
As someone who is quite conscious of the power of genetics, I was quite taken aback by this blind spot. I realized that not only did I attribute my own rather fortunate dental health (so far) to my personal behaviors, but, I had long suspected those with dental issues of less than optimal habits. Obviously environment (e.g., high sugar diet) does matter. But apparently a great deal of the variation in the trait is heritable. If you are still curious, here’s a paper which might interest you, Heritable patterns of tooth decay in the permanent dentition: principal components and factor analyses.
One of the more fascinating things about getting much of your child’s pedigree genotyped is that one can ascertain true relatedness to various relatives, rather than just expected relatedness. For example, 28% of her genome is identical by descent from my father, while 22% is from my mother. She is 26% identical by descent with one uncle, and 24% with another. More practically, the understanding of patterns realized and concrete genetic relatedness within families allows us another avenue into teasing apart heritability. Though this method has been around for more than half-a-decade, I find it curious that when I post on it some commenters immediately make objections to twin studies. Why? Because they assume that the analysis had to be a twin study because they don’t know of the genomic methodology!
But on a broader evolutionary scale, does this matter? Two of my siblings have a relatedness of 41%. In other words, as you can see in the histogram there is a wide variation in relatedness. Might this perhaps impact social relations? One can imagine genetically more similar siblings aligning against those who are dissimilar. Or not. I am skeptical that this would apply to humans, but I do wonder about organisms with larger broods. If we don’t find much variation on the scale of siblings, despite genetic variation (and therefore, likely phenotypic tells of similarity), then I would hazard to suggest that inclusive fitness is not quite the razor sharp discerning tool that some posit it is. Rather, it is part of the broader swiss army knife of behavioral ecology.
According to the reader survey 88 percent said they understood what heritability was. But only 34 percent understood the concept of additive genetic variance. For the purposes of this weblog it highlights that most people don’t understand heritability, but rather heritability. The former is the technical definition of heritability which I use on this weblog, the latter is heritability in the colloquial sense of a synonym for inheritance, biological and cultural. Almost everyone who understands the technical definition of heritability will know what heritability in the ‘narrow sense’ is, often just informally termed heritability itself. It is the proportion of phenotype variability that can be attributed to additive genetic variation. Those who understand additive genetic variance and heritability in the survey were 32 percent of readers. If you understand heritability in the technical manner you have to understand additive genetic variance. This sets the floor for the number who truly understand the concept in the way I use on this weblog (I suspect some people who were exceedingly modest who basically understand the concept for ‘government purposes’ put themselves in the ‘maybe’ category’). After nearly 10 years of blogging (the first year or so of which I myself wasn’t totally clear on the issue!) that’s actually a pretty impressive proportion. You take what you can get.
Gregory pressed, asking “Is being gay a choice?”
Pawlenty ultimately said, “I defer to the scientists in that regard.”
Again, Gregory pressed: “So you, you think it’s not a choice. … That you are, as Lady Gaga says, you’re born that way.”
Said Pawlenty: “There’s no scientific conclusion that it’s genetic. We don’t know that. So we don’t know to what extent, you know, it’s behavioral, and that’s something that’s been debated by scientists for a long time. But as I understand the science, there’s no current conclusion that it’s genetic.”
On several occasions I’ve gotten into discussions with geneticists about the possibility of reconstructing someone’s facial structure by genes alone. Combined with advances in pigmentation prediction by genetics, this could put the sketch artist out of business! But all that begs the question: how heritable are facial features anyhow? Impressionistically we know that feature are broadly heritable. This isn’t a tenuous supposition, you see the resemblance over and over across families. All that being said, what are the specific quantitative heritability estimates? How do they relate to other traits we’re interested in? This review from the early 1990s seems to have what I’m looking for, The Role of Genetics in Craniofacial Morphology and Growth. Below is a table which shows averaged heritabilities for a range of facial quantitative traits from a large number of studies:
Epigenetics is making it “big time,” Slate has a review up of the new book Epigenetics: The Ultimate Mystery of Inheritance. In case you don’t know epigenetics in terms of “what it means/why it matters” holds out the promise to break out of the genes → trait conveyor belt. Instead positing genes → trait → experience → genes, and so forth. Or perhaps more accurately genes → trait × experience → genes. Epigenetics has obviously long been overlooked as a biological phenomenon. But, I think the same could be said for the ubiquity of asexual reproduction and unicellularity! Life science exhibits anthropocentrism. That’s why there’s human genetics, and biological anthropology. My own concern is that epigenetics will give some a license to posit that the old models have been overthrown, when in fact in many cases they have been modified on the margin. Especially at the level of organisms which we’re concerned about; human-scaled eukaryotes. Humans most of all.
The last paragraph in the review highlights the hope, promise, and perils of epigenetics in regards to social relevance:
At The Intersection Chris Mooney points to new research which reiterates that 1) political ideology exhibits some heritability, 2) and, there are associations between political ideology and specific genes. I’ll set #2 aside for now, because this is a classic “more research needed” area at this point. But as I mentioned in the comments the heritability of political ideology is well known and robust. From what I can gather most people assume it’s mediated through personality traits. In the comments Chris asks:
That sounds sensible. What i find amazing is that if the heritability of politics is so robust–and I agree, it would happen via personality–why is this so widely ignored?
There are I think several issues at work. First, many people are not comfortable within imagining that beliefs which they attribute to their conscious rational choice are not only subject to social inculcation, but that may also have an element of genetic disposition. Second, most people have a poor grasp of what heritability implies. Take a look at some of Chris’ commenters. The response is generally in the “not even wrong” class. Finally, what’s the actionable component to this? In other words, what are people going to do with this sort of information?
The Pith: In this post I examine how looking at genomic data can clarify exactly how closely related siblings really are, instead of just assuming that they’re about 50% similar. I contrast this randomness among siblings to the hard & fast deterministic nature of of parent-child inheritance. Additionally, I detail how the idealized spare concepts of genetics from 100 years ago are modified by what we now know about how genes are physically organized, and, reorganized. Finally, I explain how this clarification allows us to potentially understand with greater precision the nature of inheritance of complex traits which vary within families, and across the whole population.
Humans are diploid organisms. We have two copies of each gene, inherited from each parent (the exception here is for males, who have only one X chromosome inherited from the mother, and lack many compensatory genes on the Y chromosome inherited from the father). Our own parents have two copies of each gene, one inherited from each of their parents. Therefore, one can model a grandchild from two pairs of grandparents as a mosaic of the genes of the four ancestral grandparents. But, the relationship between grandparent and grandchild is not deterministic at any given locus. Rather, it is defined by a probability. To give a concrete example, consider an individual who has four grandparents, three of whom are Chinese, one of whom is Swedish. Imagine that the Swedish individual has blue eyes. One can assume reasonably then on the locus which controls blue vs. non-blue eye color difference one of the grandparents is homozygous for the “blue eye” allele, while the other grandparents are homozygous for the “brown eye” alleles. What is the probability that any given grandchild will carry a “blue eye” allele, and so be a heterozygote? Each individual has two “slots” at a given locus. We know that on one of those slots the individual has only the possibility of having a brown eye allele. Their probability of variation then is operative only on the other slot, inherited from the parent whom we know is a heterozygote. That parent in their turn may contribute to their offspring a blue eye allele, or a brown eye allele. So there is a 50% probability that any given grandchild will be a heterozygote, and a 50% probability that they will be a homozygote.
The above “toy” example on one locus is to illustrate that the variation that one sees among individuals is in part due to the fact that we are not a “blend” of our ancestors, but a combination of various discrete genetic elements which are recombined and synthesized from generation to generation. Each sibling then can be conceptualized as a different “experiment” or “trial,” and their differences are a function of the fact that they are distinctive and unique combinations of their ancestors’ genetic variants. That is the most general theory, without any direct reference to proximate biophysical details of inheritance. Pure Mendelian abstraction as a formal model tells us that reproductive events are discrete sampling processes. But we live in the genomic age, and as you can see above we can measure the variation in genetic relationships among siblings today in an empirical sense. The expectation, as we would expect, is 0.50, but there is variance around that expectation. It is not likely that all of your siblings are “created equal” in reference to their coefficient of genetic relationship to you.
One of the interesting and robust nuggets from behavior genetics is that heritability of psychological traits increases as one ages. Imagine for example you have a cohort of individuals you follow over their lives. At the age of 1 the heritability of I.Q. may be ~20%. This means that ~20% of the variation in the population of I.Q. explained by variation in the genes of the population. More concretely, you would only expect a weak parent-offspring correlation in I.Q. in this sample. At the age of 10 the heritability of I.Q. in the same sample may be ~40%, and in mature adulthood it may rise to ~80% (those are real numbers which I’ve borrowed from Robert Plomin). Many people find this result rather counterintuitive. How can a trait like intelligence become “more genetic”?
Remember that I’m talking about heritability here, not an ineffable “more” or “less” quantum of “genetic” aspect of a trait. In other words: does variation in genes due to different parental backgrounds matter for a trait? Second, the nature of psychological traits is somewhat slippery and plastic. As I’ve noted before the correlation between a score on a 10-world vocabulary test and general intelligence is pretty good. You can expect people with high scores on the vocabulary test to have higher I.Q.’s than those who have low scores. But if you take an individual and lock them in a room without human contact for their first 15 years, they are unlikely to exhibit any such correspondence. You don’t have to be a rocket scientist to understand why. Quantitative behavior genetic traits are complex and are subject to a host of background conditions, and express themselves in an environmental context.
Since the beginning of this weblog (I’ve been writing for eight years) heritability has been a major confusion. Even long time readers misunderstand what I’m trying to get at when I talk about heritability. That’s why posts such as Mr. Luke Jostins‘ are so helpful. I had seen references to a piece online, The Causes of Common Diseases are Not Genetic Concludes a New Analysis, but I hadn’t given it much thought. Until Ms. Mary Carmichael’s post DNA, Denial, and the Rise of “Environmental Determinism”. She begins:
Michael Pollan, the well-known writer on food and agriculture, is a smart guy. His arguments tend to be nuanced and grounded in common sense. I like his basic maxim on nutrition – “Eat food. Not too much. Mostly plants” – so much that I recently promoted it in a Newsweek cover story. He’s the last person I’d suspect of reactionary thinking, which is why I wish I didn’t have to say this: Michael Pollan has made a deeply unfortunate mistake.
A few days ago, speaking to his 43,000 followers on Twitter, Pollan linked to an essay written by an environmental advocacy group that spends much of its time fighting the depradations of Big Agriculture. Curiously, the essay wasn’t about ecological destruction or even about agriculture. It was about human genetics. It argued that since genetics currently can’t explain everything about inheritance, genes must not influence the development of disease, and thus the causes of illness must be overwhelmingly environmental (meaning “uninherited” as opposed to “caused by pollution,” though the latter category of factors is part of the former one). This was a little like arguing that your engine doesn’t power your car because sometimes it breaks down in a way that confuses your mechanic — and concluding that gasoline alone is sufficient to make a car with no engine run. But Pollan took the argument at face value. He said it showed “how the gene-disease paradigm appears to be collapsing.” He was troubled that its contentions apparently had gone unnoticed: “Why aren’t we hearing about this?!”
Of course I had seen Dr. Daniel MacArthur’s post Bioscience Resource Project critique of modern genomics: a missed opportunity in my RSS, but when I started reading the rebuttal I immediately thought “Dr. Dan’s interlocutors sound kind of dumb,” and I stopped reading. After reading the post I don’t think they’re dumb, I think they’re being lawyerly. Much of the piece is a rhetorical tour de force in leveraging the prejudices and biases of the intended readership. This is the Intelligent Design version of Left-wing “Blank Slate” Creationism.* They smoothly manipulate real findings in a deceptive shell game intended to convince the public, and shape public policy. Their success is evident in Pollan’s response. “X paradigm appears to be collapsing.” “Why aren’t we hearing about this?” Does this sound familiar? Like Dr. MacArthur I think some of the criticisms within the piece are valid. Despite not being hostile to the maxim “better living through chemistry,” I do think that there has been an excessive trend toward pharmaceutical or surgical “cures” in relation to diseases of lifestyle (anti-depressants, gastric bypass, etc.). But we go down a very dangerous path when we make recourse to shoddy means toward ostensibly admirable ends. This sort of discourse is not sustainable! (just used a buzzword intended to appeal right there!)
I honestly can’t be bothered to say much more when so many others already have. This is a boat I missed. But if some of what I say above isn’t clear, I recommend you read the original essay. Then read Dr. MacArthur and Ms. Carmichael. If you’re hungry for more, Ms. Carmichael has a helpful list of links.
* Left Creationism had its most negative manifestation as Lysenkoism, but it suffuses the outlook of many who fear the emergence of a new Nazi abomination. Leon Kamin in the 1970s even claimed that IQ was not heritable at all! Though he backed off such an extreme position, it shows how confident he was that could claim such a thing.
I recall projections in the early 2000s that 25% of the American population would be employed as systems administrators circa 2020 if rates of employment growth at that time were extrapolated. Obviously the projections weren’t taken too seriously, and the pieces were generally making fun of the idea that IT would reduce labor inputs and increase productivity. I thought back to those earlier articles when I saw a new letter in Nature in my RSS feed this morning, Hundreds of variants clustered in genomic loci and biological pathways affect human height:
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits1, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait2, 3. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
The supplements run to nearly 100 pages, and the author list is enormous. But at least the supplements are free to all, so you should check them out. There are a few sections of the paper proper that are worth passing on though if you can’t get beyond the paywall.