neurofibromatosis

Evolution: Foundations of Genetics

PNRJ Logic of Kindness, tribal paradigm , , , , , , , , , , , ,


Jan 26 JDN 2460702

It frustrates me that in American society, evolutionary biology is considered a controversial topic. When I use knowledge from quantum physics or from organic chemistry, all I need to do is cite a credible source; I don’t need to preface it with a defense of the entire scientific field. Yet in the United States today, even basic statements of facts observed in evolutionary biology are met with incredulity. The consensus in the scientific community about evolution is greater than the consensus about quantum physics, and comparable to the consensus about organic chemistry. 95% of scientists agree that evolution happens, that Darwinian natural selection is the primary cause, and that human beings share a common ancestor with every other life form on Earth. Polls of scientists have consistently made this clear, and the wild success of Project Steve continues to vividly demonstrate it.

But I would rather defend evolution than have to tiptoe around it, or worse have my conclusions ignored because I use it. So, here goes.

You may think you understand evolution, but especially if you doubt that evolution is true, odds are good that you really don’t. Even most people who have taken college courses in evolutionary biology have difficulty understanding evolution.

Evolution is a very rich and complicated science, and I don’t have room to do it justice here. I merely hope that I can give you enough background to make sense of the core concepts, and convince you that evolution is real and important.

Foundations of genetics

So let us start at the beginning. DNA—deoxyribonucleic acid—is a macromolecular (very big and complicated) organic (carbon-based) acid (chemical that can give up hydrogen ions in solution) that is produced by all living cells. More properly, it is a class of macromolecular organic acids, because differences between DNA strands are actually chemical differences in the molecule. The structure of DNA consists of two long chains of constituent molecules called nucleotides; for chemical reasons nucleotides usually bond in pairs, adenine (A) with thymine (T), guanine (G) with cytosine (C). Pairs of nucleotides are called base pairs. We call it a “double-helix” because the two chains are normally wrapped around each other in a helix shape.

Because of this base-pair correspondence, the two strands of a DNA molecule are complementary; if one half is GATTACA, the other half will be CTAATGT. This process is reversible. Either strand can be reproduced from the other; this is how DNA replicates. A DNA strand GATTACA/CTAATGT can split into its GATTACA half and its CTAATGT half, and then the original GATTACA half will acquire new nucleotides and make a new CTAATGT for itself; similarly the original CTAATGT half will make a new GATTACA. At the end of this process, two precise copies of the original GATTACA/CTAATGT strand will result. This process can be repeated as necessary.

DNA molecules can vary in size from a few base-pairs (like the sequence GATTACA), to the 16,000 base-pairs of Carsonella bacteria, up to the 3 billion base-pairs of humans and beyond. While complexity of DNA and complexity of organism are surely related (it’s impossible to make a really complicated organism with very simple DNA), more base pairs does not necessarily imply a more complex organism. The single-celled amoeboid Polychaos dubium has 670 billion base-pairs. Amoeboids are relatively complex, all things considered; but they’re hardly 200 times more complex than we are!

The copying of DNA is exceedingly precise, but like anything in real life, not perfect. Cells have many physical and chemical mechanisms to correct bad copying, but sometimes—about 1 in 1 million base-pairs copied—something goes wrong. Sometimes, one nucleotide gets switched for another; perhaps what should have been a T becomes an A, or what should have been an A becomes a G. Other times, a whole sequence of DNA gets duplicated and inserted in a new place; still other times entire pieces of DNA are lost, never to be copied again. In some cases a sequence is flipped around backwards. All of these things (a single-nucleotide substitution, an insertion, a deletion, and an inversion, respectively) are forms of mutation. Mutation is always happening, but it can be increased by the presence of radiation, toxins, and other stresses. Usually cells with mutant DNA are killed by the immune system; if not, mutant body cells can cause cancer or other health problems. Usually it’s only mutations in gametes—the sperm and egg cells that carry DNA to the next generation—that actually have a long-term effect on future generations. Most mutations do not have any significant effect, and most of those that do have bad effects. It is only the rare minority of mutations that actually produces something useful to an organism’s survival.

What does DNA do? It makes proteins. Technically, proteins make other proteins (enzymes called transcriptases and polymerases and so on), but which protein is produced by such a process is dependent upon the order of base pairs in a DNA strand. DNA has been likened to a “code” or a “message”, but this is a little misleading. It’s definitely a sequence that contains information, but the “code” is less like a cryptographer’s cipher and more like a computer’s machine code; it interacts directly with the hardware to produce an output. And it’s important to understand that when DNA is “read” and “decoded”, it’s all happening purely by chemical reactions, and there is no conscious being doing the reading. While metaphorically we might say that DNA is a “code” or a “language”, we must not take these metaphors too literally; DNA is not a language in the same sense as English, nor is it a code in the same sense as the Enigma cipher.

Genotype and phenotype

DNA is also not a “blueprint”, as it is sometimes described. There is a one-to-one correspondence between a house and its blueprint: given a house, it would be easy to draw a blueprint much like the original blueprint; given a blueprint, one can construct basically the same house. DNA is not like this. There is no one-to-one correspondence between DNA and a living organism’s structure. Given the traits of an organism, it is impossible to reconstruct its DNA—and purely from the DNA, it is impossible to reconstruct the organism. A better analogy is to a recipe, which offers a general guide as to what to make and how to make it, but depending on the cook and the ingredients, may give quite different results. The ingredients in this case are nutrients, and the “cook” is the whole of our experience and interaction with the environment. No experience or environment can act upon us unless we have the right genes and nutrients to make it effective. No matter how long you let it sit, bread with no yeast will never rise—and no matter how hard you try to teach him, your dog will never be able to speak in fluent sentences.

Furthermore, genes rarely do only one thing in an organism; much as drugs have side effects, so do genes, a phenomenon called pleiotropy. Some genes are more pleiotropic than others, but really, all genes are pleiotropic. In any complex organism, genes will have complex effects. The genes of an organism are its genotype; the actual traits that it has are its phenotype. We have these two different words precisely because they are different things; genotype influences phenotype, but many other things influence phenotype besides genotype. The answer to the question “Nature or Nurture?” is always—always—“Both”. There are much more useful questions to ask, like “How much of the variation of this trait within this population is attributable to genetic differences?”, “How do environmental conditions trigger this phenotype in the presence of this genotype?”, and “Under what ecological circumstances would this genotype evolve?”

This is why it’s a bit misleading to talk about the “the gene for homosexuality” or “the gene for religiosity”; taken literally this would be like saying “the ingredient for chocolate cake” or “the beam for the Empire State Building”. At best we can distinguish certain genes that might, in the context of many other genes and environmental contributions, make a difference between particular states—much as removing the cocoa from chocolate cake makes some other kind of cake, it could be that removing a particular gene from someone strongly homosexual might make them nearer to heterosexual. It’s not that genes can be mapped one-to-one to traits of an organism; but rather that in many cases a genetic difference corresponds to a difference in traits that is ecologically significant. This is what geneticists mean when they say “the gene for X”; it’s a very useful concept in evolutionary theory, but I don’t think it’s one most laypeople understand. As usual, Richard Dawkins explains this matter brilliantly:

Probably the first point to make is that whenever a geneticist speaks of a gene `for’ such and such a characteristic, say brown eyes, he never means that this gene affects nothing else, nor that it is the only gene contributing to the brown pigmentation. Most genes have many distantly ramified and apparently unconnected effects. A vast number of genes are necessary for the development of eyes and their pigment. When a geneticist talks about a single gene effect, he is always talking about a difference between individuals. A gene `for brown eyes’ is not a gene that, alone and unaided, manufactures brown pigment. It is a gene that, when compared with its alleles (alternatives at the same chromosomal locus), in a normal environment, is responsible for the difference in eye colour between individuals possessing the gene and individuals not possessing the gene. The statement `G1 is a gene for phenotypic characteristic P1‘ is always a shorthand. It always implies the existence, or potential existence, of at least one alternative gene G2, and at least one alternative characteristic P2. It also implies a normal developmental environment, including the presence of the other genes which are common in the gene pool as a whole, and therefore likely to be in the same body. If all individuals had two copies of the gene `for’ brown eyes and if no other eye colour ever occurred, the `gene for brown eyes’ would strictly be a meaningless concept. It can only be defined by reference to at least one potential alternative. Of course any gene exists physically in the sense of being a length of DNA; but it is only properly called a gene `for X’ if there is at least one alternative gene at the same chromosomal locus, which leads to not X.

It follows that there is no clear limit to the complexity of the `X’ which we may substitute in the phrase `a gene for X’. Reading, for example, is a learned skill of immense and subtle complexity. A gene for reading would, to naive common sense, be an absurd notion. Yet, if we follow genetic terminological convention to its logical conclusion, all that would be necessary in order to establish the existence of a gene for reading is the existence of a gene for not reading. If a gene G2 could be found which infallibly caused in its possessors the particular brain lesion necessary to induce specific dyslexia, it would follow that G1, the gene which all the rest of us have in double dose at that chromosomal locus, would by definition have to be called a gene for reading.

It’s important to keep this in mind when interpreting any new ideas or evidence from biology. Just as cocoa by itself is not chocolate cake because one also needs all the other ingredients that make it cake in the first place, “the gay gene” cannot exist in isolation because in order to be gay one needs all the other biological and neurological structures that make one a human being in the first place. Moreover, just as cocoa changes the consistency of a cake so that other ingredients may need to be changed to compensate, so a hypothetical“gay gene” might have other biological or neurological effects that would be inseparable from its contribution to sexual orientation.

It’s also important to point out that hereditary is not the same thing as genetic. By comparing pedigrees, it is relatively straightforward to determine the heritability of a trait within a population—but this is not the same as determining whether the trait is genetic. A great many traits are systematically inherited from parents that have nothing to do with DNA—like language, culture, and wealth. (These too can evolve, but it’s a different kind of evolution.) In the United States, IQ is about 80% heritable; but so is height, and yet nutrition has large, well-documented effects on height (The simplest case: malnourished people never grow very tall). If, as is almost certainly the case, there are many environmental influences such as culture and education that can affect IQ scores, then the heritability of IQ tells us very little.

In fact, some traits are genetic but not hereditary! Certain rare genetic diseases can appear by what is called de novo mutation; the genes that cause them can randomly appear in an individual without having been present in their parents. Neurofibromatosis occurs in as many people with no family history as it does in people with family history; and yet, neurofibromatosis is definitely a genetic disorder, for it can be traced to particular sections of defective DNA.

Honestly, most of the debate about nature versus nurture in human behavior is really quite pointless. Even if you ignore the general facts that phenotype is always an interaction between genes and environment, and feedback occurs between genes and environment over evolutionary time, human beings are the species for which the “Nature or nurture?” question reaches its most meaningless. It is human nature to be nurtured; it is written within our genes that we should be flexible, intelligent beings capable of learning and training far beyond our congenital capacities. An ant’s genes are not written that way; ants play out essentially the same program in every place and time, because that program is hard-wired within them. Humans have an enormous variety of behaviors—far outstripping the variety in any other species—despite having genetic variation of only about 0.1%; clearly most of the differences between humans are environmental. Yet, it is precisely the genes that code for being Homo sapiens that make this possible; if we’d had the genes of an ant or an earthworm, we wouldn’t have this enormous behavioral plasticity. So each person is who they are largely because of their environment—but that itself would not be true without the genes we all share.

Nature via Nurture

PNRJ cognitive science, core principles , , , , , , , , , , , , , , , , , , , , , , , ,

JDN 2457222 EDT 16:33.

One of the most common “deep questions” human beings have asked ourselves over the centuries is also one of the most misguided, the question of “nature versus nurture”: Is it genetics or environment that makes us what we are?

Humans are probably the single entity in the universe for which this question makes least sense. Artificial constructs have no prior existence, so they are “all nurture”, made what we choose to make them. Most other organisms on Earth behave accordingly to fixed instinctual programming, acting out a specific series of responses that have been honed over millions of years, doing only one thing, but doing it exceedingly well. They are in this sense “all nature”. As the saying goes, the fox knows many things, but the hedgehog knows one very big thing. Most organisms on Earth are in this sense hedgehogs, but we Homo sapiens are the ultimate foxes. (Ironically, hedgehogs are not actually “hedgehogs” in this sense: Being mammals, they have an advanced brain capable of flexibly responding to environmental circumstances. Foxes are a good deal more intelligent still, however.)

But human beings are by far the most flexible, adaptable organism on Earth. We live on literally every continent; despite being savannah apes we even live deep underwater and in outer space. Unlike most other species, we do not fit into a well-defined ecological niche; instead, we carve our own. This certainly has downsides; human beings are ourselves a mass extinction event.

Does this mean, therefore, that we are tabula rasa, blank slates upon which anything can be written?

Hardly. We’re more like word processors. Staring (as I of course presently am) at the blinking cursor of a word processor on a computer screen, seeing that wide, open space where a virtual infinity of possible texts could be written, depending entirely upon a sequence of miniscule key vibrations, you could be forgiven for thinking that you are looking at a blank slate. But in fact you are looking at the pinnacle of thousands of years of technological advancement, a machine so advanced, so precisely engineered, that its individual components are one ten-thousandth the width of a human hair (Intel just announced that we can now do even better than that). At peak performance, it is capable of over 100 billion calculations per second. Its random-access memory stores as much information as all the books on a stacks floor of the Hatcher Graduate Library, and its hard drive stores as much as all the books in the US Library of Congress. (Of course, both libraries contain digital media as well, exceeding anything my humble hard drive could hold by a factor of a thousand.)

All of this, simply to process text? Of course not; word processing is an afterthought for a processor that is specifically designed for dealing with high-resolution 3D images. (Of course, nowadays even a low-end netbook that is designed only for word processing and web browsing can typically handle a billion calculations per second.) But there the analogy with humans is quite accurate as well: Written language is about 10,000 years old, while the human visual mind is at least 100,000. We were 3D image analyzers long before we were word processors. This may be why we say “a picture is worth a thousand words”; we process each with about as much effort, even though the image necessarily contains thousands of times as many bits.

Why is the computer capable of so many different things? Why is the human mind capable of so many more? Not because they are simple and impinged upon by their environments, but because they are complex and precision-engineered to nonlinearly amplify tiny inputs into vast outputs—but only certain tiny inputs.

That is, it is because of our nature that we are capable of being nurtured. It is precisely the millions of years of genetic programming that have optimized the human brain that allow us to learn and adapt so flexibly to new environments and form a vast multitude of languages and cultures. It is precisely the genetically-programmed humanity we all share that makes our environmentally-acquired diversity possible.

In fact, causality also runs the other direction. Indeed, when I said other organisms were “all nature” that wasn’t right either; for even tightly-programmed instincts are evolved through millions of years of environmental pressure. Human beings have even been involved in cultural interactions long enough that it has begun to affect our genetic evolution; the reason I can digest lactose is that my ancestors about 10,000 years ago raised goats. We have our nature because of our ancestors’ nurture.

And then of course there’s the fact that we need a certain minimum level of environmental enrichment even to develop normally; a genetically-normal human raised into a deficient environment will suffer a kind of mental atrophy, as when children raised feral lose their ability to speak.

Thus, the question “nature or nurture?” seems a bit beside the point: We are extremely flexible and responsive to our environment, because of innate genetic hardware and software, which requires a certain environment to express itself, and which arose because of thousands of years of culture and millions of years of the struggle for survival—we are nurture because nature because nurture.

But perhaps we didn’t actually mean to ask about human traits in general; perhaps we meant to ask about some specific trait, like spatial intelligence, or eye color, or gender identity. This at least can be structured as a coherent question: How heritable is the trait? What proportion of the variance in this population is caused by genetic variation? Heritability analysis is a well-established methodology in behavioral genetics.
Yet, that isn’t the same question at all. For while height is extremely heritable within a given population (usually about 80%), human height worldwide has been increasing dramatically over time due to environmental influences and can actually be used as a measure of a nation’s economic development. (Look at what happened to the height of men in Japan.) How heritable is height? You have to be very careful what you mean.

Meanwhile, the heritability of neurofibromatosis is actually quite low—as many people acquire the disease by new mutations as inherit it from their parents—but we know for a fact it is a genetic disorder, because we can point to the specific genes that mutate to cause the disease.

Heritability also depends on the population under consideration; speaking English is more heritable within the United States than it is across the world as a whole, because there are a larger proportion of non-native English speakers in other countries. In general, a more diverse environment will lead to lower heritability, because there are simply more environmental influences that could affect the trait.

As children get older, their behavior gets more heritable—a result which probably seems completely baffling, until you understand what heritability really means. Your genes become a more important factor in your behavior as you grow up, because you become separated from the environment of your birth and immersed into the general environment of your whole society. Lower environmental diversity means higher heritability, by definition. There’s also an effect of choosing your own environment; people who are intelligent and conscientious are likely to choose to go to college, where they will be further trained in knowledge and self-control. This latter effect is called niche-picking.

This is why saying something like “intelligence is 80% genetic” is basically meaningless, and “intelligence is 80% heritable” isn’t much better until you specify the reference population. The heritability of intelligence depends very much on what you mean by “intelligence” and what population you’re looking at for heritability. But even if you do find a high heritability (as we do for, say, Spearman’s g within the United States), this doesn’t mean that intelligence is fixed at birth; it simply means that parents with high intelligence are likely to have children with high intelligence. In evolutionary terms that’s all that matters—natural selection doesn’t care where you got your traits, only that you have them and pass them to your offspring—but many people do care, and IQ being heritable because rich, educated parents raise rich, educated children is very different from IQ being heritable because innately intelligent parents give birth to innately intelligent children. If genetic variation is systematically related to environmental variation, you can measure a high heritability even though the genes are not directly causing the outcome.

We do use twin studies to try to sort this out, but because identical twins raised apart are exceedingly rare, two very serious problems emerge: One, there usually isn’t a large enough sample size to say anything useful; and more importantly, this is actually an inaccurate measure in terms of natural selection. The evolutionary pressure is based on the correlation with the genes—it actually doesn’t matter whether the genes are directly causal. All that matters is that organisms with allele X survive and organisms with allele Y do not. Usually that’s because allele X does something useful, but even if it’s simply because people with allele X happen to mostly come from a culture that makes better guns, that will work just as well.

We can see this quite directly: White skin spread across the world not because it was useful (it’s actually terrible in any latitude other than subarctic), but because the cultures that conquered the world happened to be comprised mostly of people with White skin. In the 15th century you’d find a very high heritability of “using gunpowder weapons”, and there was definitely a selection pressure in favor of that trait—but it obviously doesn’t take special genes to use a gun.

The kind of heritability you get from twin studies is answering a totally different, nonsensical question, something like: “If we reassigned all offspring to parents randomly, how much of the variation in this trait in the new population would be correlated with genetic variation?” And honestly, I think the only reason people think that this is the question to ask is precisely because even biologists don’t fully grasp the way that nature and nurture are fundamentally entwined. They are trying to answer the intuitive question, “How much of this trait is genetic?” rather than the biologically meaningful “How strongly could a selection pressure for this trait evolve this gene?”

And if right now you’re thinking, “I don’t care how strongly a selection pressure for the trait could evolve some particular gene”, that’s fine; there are plenty of meaningful scientific questions that I don’t find particularly interesting and are probably not particularly important. (I hesitate to provide a rigid ranking, but I think it’s safe to say that “How does consciousness arise?” is a more important question than “Why are male platypuses venomous?” and “How can poverty be eradicated?” is a more important question than “How did the aircraft manufacturing duopoly emerge?”) But that’s really the most meaningful question we can construct from the ill-formed question “How much of this trait is genetic?” The next step is to think about why you thought that you were asking something important.

What did you really mean to ask?

For a bald question like, “Is being gay genetic?” there is no meaningful answer. We could try to reformulate it as a meaningful biological question, like “What is the heritability of homosexual behavior among males in the United States?” or “Can we find genetic markers strongly linked to self-identification as ‘gay’?” but I don’t think those are the questions we really meant to ask. I think actually the question we meant to ask was more fundamental than that: Is it legitimate to discriminate against gay people? And here the answer is unequivocal: No, it isn’t. It is a grave mistake to think that this moral question has anything to do with genetics; discrimination is wrong even against traits that are totally environmental (like religion, for example), and there are morally legitimate actions to take based entirely on a person’s genes (the obvious examples all coming from medicine—you don’t treat someone for cystic fibrosis if they don’t actually have it).

Similarly, when we ask the question “Is intelligence genetic?” I don’t think most people are actually interested in the heritability of spatial working memory among young American males. I think the real question they want to ask is about equality of opportunity, and what it would look like if we had it. If success were entirely determined by intelligence and intelligence were entirely determined by genetics, then even a society with equality of opportunity would show significant inequality inherited across generations. Thus, inherited inequality is not necessarily evidence against equality of opportunity. But this is in fact a deeply disingenuous argument, used by people like Charles Murray to excuse systemic racism, sexism, and concentration of wealth.

We didn’t have to say that inherited inequality is necessarily or undeniably evidence against equality of opportunity—merely that it is, in fact, evidence of inequality of opportunity. Moreover, it is far from the only evidence against equality of opportunity; we also can observe the fact that college-educated Black people are no more likely to be employed than White people who didn’t even finish high school, for example, or the fact that otherwise identical resumes with predominantly Black names (like “Jamal”) are less likely to receive callbacks compared to predominantly White names (like “Greg”). We can observe that the same is true for resumes with obviously female names (like “Sarah”) versus obviously male names (like “David”), even when the hiring is done by social scientists. We can directly observe that one-third of the 400 richest Americans inherited their wealth (and if you look closer into the other two-thirds, all of them had some very unusual opportunities, usually due to their family connections—“self-made” is invariably a great exaggeration). The evidence for inequality of opportunity in our society is legion, regardless of how genetics and intelligence are related. In fact, I think that the high observed heritability of intelligence is largely due to the fact that educational opportunities are distributed in a genetically-biased fashion, but I could be wrong about that; maybe there really is a large genetic influence on human intelligence. Even so, that does not justify widespread and directly-measured discrimination. It does not justify a handful of billionaires luxuriating in almost unimaginable wealth as millions of people languish in poverty. Intelligence can be as heritable as you like and it is still wrong for Donald Trump to have billions of dollars while millions of children starve.

This is what I think we need to do when people try to bring up a “nature versus nurture” question. We can certainly talk about the real complexity of the relationship between genetics and environment, which I think are best summarized as “nature via nurture”; but in fact usually we should think about why we are asking that question, and try to find the real question we actually meant to ask.