Tag: Genetics

The Founder Principle: A Wonderful Idea from Biology

We've all been taught natural selection; the mechanism by which species evolve through differential reproductive success. Most of us are familiar with the idea that random mutations in DNA cause variances in offspring, some of which survive more frequently than others. However, this is only part of the story.

Sometimes other situations cause massive changes in species populations, and they're often more nuanced and tough to spot.

One such concept comes from one of the most influential biologists in history, Ernst Mayr. He called it The Founder Principle, a mechanism by which new species are created by a splintered population; often with lower genetic diversity and an increased risk of extinction.

In the brilliant The Song of the Dodo: Island Biography in an Age of ExtinctionDavid Quammen gives us not only the stories of many brilliant biological naturalists including Mayr, but we also get a deep dive into the core concepts of evolution and extinction, including the founder principle.

Quammen begins by outlining the basic idea:

When a new population is founded in an isolated place, the founders usually constitute a numerically tiny group – a handful of lonely pioneers, or just a pair, or maybe no more than one pregnant female. Descending from such a small number of founders, the new population will carry only a minuscule and to some extent random sample of the gene pool of the base population. The sample will most likely be unrepresentative, encompassing less genetic diversity than the larger pool. This effect shows itself whenever a small sample is taken from a large aggregation of diversity; whether the aggregation consists of genes, colored gum balls, M&M’s, the cards of a deck, or any other collection of varied items, a small sample will usually contain less diversity than the whole.

Why does the founder principle happen? It's basically applied probability. Perhaps an example will help illuminate the concept.

Think of yourself playing a game of poker (five card draw) with a friend. The deck of cards is separated into four suits: Diamonds, hearts, clubs and spades, each suit having 13 cards for a total of 52 cards.

Now look at your hand of five cards. Do you have one card from each suit? Maybe. Are all five cards from the same suit? Probably not, but it is possible. Will you get the ace of spades? Maybe, but not likely.

This is a good metaphor for how the founder principle works. The gene pool carried by a small group of founders is unlikely to be precisely representative of the gene pool of the larger group. In some rare cases it will be very unrepresentative, like you getting dealt a straight flush.

It starts to get interesting when this founder population starts to reproduce, and genetic drift causes the new population to diverge significantly from its ancestors. Quammen explains:

Already isolated geographically from its base population, the pioneer population now starts drifting away genetically. Over the course of generations, its gene pool becomes more and more different from the gene pool of the base population – different both as to the array of alleles (that is, the variant forms of a given gene) and as to the commonness of each allele.

The founder population, in some cases, will become so different that it can no longer mate with the original population. This new species may even be a competitor for resources if the two populations are ever reintroduced. (Say, if a land bridge is created between two islands, or humans bring two species back in contact.)

Going back to our card metaphor, let’s pretend that you and your friend are playing with four decks of cards — 208 total cards. Say we randomly pulled out forty cards from those decks. If there are absolutely no kings in the forty cards you are playing with, you will never be able to create a royal flush (ace+king+queen+jack+10 of the same suit). It doesn’t matter how the cards are dealt, you can never make a royal flush with no kings.

Thus it is with species: If a splintered-off population isn’t carrying a specific gene variant (allele), that variant can never be represented in the newly created population, no matter how prolific that gene may have been in the original population. It's gone. And as the rarest variants disappear, the new population becomes increasingly unlike the old one, especially if the new population is small.

Some alleles are common within a population, some are rare. If the population is large, with thousands or millions of parents producing thousands or millions of offspring, the rare alleles as well as the common ones will usually be passed along. Chance operation at high numbers tends to produce stable results, and the proportions of rarity and commonness will hold steady. If the population is small, though, the rare alleles will most likely disappear […] As it loses its rare alleles by the wayside, a small pioneer population will become increasingly unlike the base population from which it derived.

Some of this genetic loss may be positive (a gene that causes a rare disease may be missing), some may be negative (a gene for a useful attribute may be missing) and some may be neutral.

The neutral ones are the most interesting: A neutral gene at one point in time may become a useful gene at another point. It's like playing a round of poker where 8’s are suddenly declared “wild,” and that card suddenly becomes much more important than it was the hand before. The same goes for animal traits.

Take a mammal population living on an island, having lost all of its ability to swim. That won’t mean much if all is well and it is never required to swim. But the moment there is a natural disaster such as a fire, having the ability to swim the short distance to the mainland could be the difference between survival or extinction.

That's why the founder principle is so dangerous: The loss of genetic diversity often means losing valuable survival traits. Quammen explains:

Genetic drift compounds the founder-effect problem, stripping a small population of the genetic variation that it needs to continue evolving. Without that variation, the population stiffens toward uniformity. It becomes less capable of adaptive response. There may be no manifest disadvantages in uniformity so long as environmental circumstances remain stable; but when circumstances are disrupted, the population won’t be capable of evolutionary adjustment. If the disruption is drastic, the population may go extinct.

This loss of adaptability is one of the two major issues caused by the founder principle, the second being inbreeding depression. A founder population may have no choice but to only breed within its population and a symptom of too much inbreeding is the manifestation of harmful genetic variants among inbred individuals. (One reason humans consider incest a dangerous activity.) This too increases the fragility of species and decreases their ability to evolve.

The founder principle is just one of many amazing ideas in The Song of the Dodo. In fact, we at Farnam Street feel the book is so important that it made our list of books we recommend to improve your general knowledge of the world and it was the first book we picked for our learning community reading group.

If you have already read this book and want more we suggest Quammen’s The Reluctant Mr. Darwin or his equally thought provoking Spillover: Animal Infections and the Next Human Pandemic. Another wonderful and readable book on species evolution is The Beak of the Finch, by Jonathan Weiner.

Our Genes and Our Behavior

“But now we are starting to show genetic influence on individual differences using DNA. DNA is a game changer; it's a lot harder to argue with DNA than it is with a twin study or an adoption study.”
— Robert Plomin

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It's not controversial to say that our genetics help explain our physical traits. Tall parents will, on average, have tall children. Overweight parents will, on average, have overweight children. Irish parents have Irish looking kids. This is true to the point of banality and only a committed ignorant would dispute it.

It's slightly more controversial to talk about genes influencing behavior. For a long time, it was denied entirely. For most of the 20th century, the “experts” in human behavior had decided that “nurture” beat “nature” with a score of 100-0. Particularly influential was the child's early life — the way their parents treated them in the womb and throughout early childhood. (Thanks Freud!)

So, where are we at now?

Genes and Behavior

Developmental scientists and behavioral scientists eventually got to work with twin studies and adoption studies, which tended to show that certain traits were almost certainly heritable and not reliant on environment, thanks to the natural controlled experiments of twins separated at birth. (This eventually provided fodder for Judith Rich Harris's wonderful work on development and personality.)

All throughout, the geneticists, starting with Gregor Mendel and his peas, kept on working. As behavioral geneticist Robert Plomin explains, the genetic camp split early on. Some people wanted to understand the gene itself in detail, using very simple traits to figure it out (eye color, long or short wings, etc.) and others wanted to study the effect of genes on complex behavior, generally:

People realized these two views of genetics could come together. Nonetheless, the two worlds split apart because Mendelians became geneticists who were interested in understanding genes. They would take a convenient phenotype, a dependent measure, like eye color in flies, just something that was easy to measure. They weren't interested in the measure, they were interested in how genes work. They wanted a simple way of seeing how genes work.

By contrast, the geneticists studying complex traits—the Galtonians—became quantitative geneticists. They were interested in agricultural traits or human traits, like cardiovascular disease or reading ability, and would use genetics only insofar as it helped them understand that trait. They were behavior centered, while the molecular geneticists were gene centered. The molecular geneticists wanted to know everything about how a gene worked. For almost a century these two worlds of genetics diverged.

Eventually, the two began to converge. One camp (the gene people) figured out that once we could sequence the genome, they might be able to understand more complicated behavior by looking directly at genes in specific people with unique DNA, and contrasting them against one another.

The reason why this whole gene-behavior game is hard is because, as Plomin makes clear, complex traits like intelligence are not like eye color. There's no “smart gene” — it comes from the interaction of thousands of different genes and can occur in a variety of combinations. Basic Mendel-style counting (the sort of dominant/recessive eye color gene thing you learned in high school biology) doesn't work in analyzing the influence of genes on complex traits:

The word gene wasn't invented until 1903. Mendel did his work in the mid-19th century. In the early 1900s, when Mendel was rediscovered, people finally realized the impact of what he did, which was to show the laws of inheritance of a single gene. At that time, these Mendelians went around looking for Mendelian 3:1 segregation ratios, which was the essence of what Mendel showed, that inheritance was discreet. Most of the socially, behaviorally, or agriculturally important traits aren't either/or traits, like a single-gene disorder. Huntington's disease, for example, is a single-gene dominant disorder, which means that if you have that mutant form of the Huntington's gene, you will have Huntington's disease. It's necessary and sufficient. But that's not the way complex traits work.

The importance of genetics is hard to understate, but until the right technology came along, we could only observe it indirectly. A study might have shown that 50% of the variance in cognitive ability was due to genetics, but we had no idea which specific genes, in which combinations, actually produced smarter people.

But the Moore's law style improvement in genetic testing means that we can cheaply and effectively map out entire genomes for a very low cost. And with that, the geneticists have a lot of data to work with, a lot of correlations to begin sussing out. The good thing about finding strong correlations between genes and human traits is that we know which one is causative: The gene! Obviously, your reading ability doesn't cause you to have certain DNA; it must be the other way around. So “Big Data” style screening is extremely useful, once we get a little better at it.

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The problem is that, so far, the successes have been a bit minimal. There are millions of “ATCG” base pairs to check on.  As Plomin points out, we can only pinpoint about 20% of the specific genetic influence for something simple like height, which we know is about 90% heritable. Complex traits like schizophrenia are going to take a lot of work:

We've got to be able to figure out where the so-called missing heritability is, that is, the gap between the DNA variants that we are able to identify and the estimates we have from twin and adoption studies. For example, height is about 90 percent heritable, meaning, of the differences between people in height, about 90 percent of those differences can be explained by genetic differences. With genome-wide association studies, we can account for 20 percent of the variance of height, or a quarter of the heritability of height. That's still a lot of missing heritability, but 20 percent of the variance is impressive.

With schizophrenia, for example, people say they can explain 15 percent of the genetic liability. The jury is still out on how that translates into the real world. What you want to be able to do is get this polygenic score for schizophrenia that would allow you to look at the entire population and predict who's going to become schizophrenic. That's tricky because the studies are case-control studies based on extreme, well-diagnosed schizophrenics, versus clean controls who have no known psychopathology. We'll know soon how this polygenic score translates to predicting who will become schizophrenic or not.

It brings up an interesting question that gets us back to the beginning of the piece: If we know that genetics have an influence on some complex behavioral traits (and we do), and we can with the continuing progress of science and technology, sequence a baby's genome and predict to a certain extent their reading level, facility with math, facility with social interaction, etc., do we do it?

Well, we can't until we get a general recognition that genes do indeed influence behavior and do have predictive power as far as how children perform. So far, the track record on getting educators to see that it's all quite real is pretty bad. Like the Freudians before, there's a resistance to the “nature” aspect of the debate, probably influenced by some strong ideologies:

If you look at the books and the training that teachers get, genetics doesn't get a look-in. Yet if you ask teachers, as I've done, about why they think children are so different in their ability to learn to read, and they know that genetics is important. When it comes to governments and educational policymakers, the knee-jerk reaction is that if kids aren't doing well, you blame the teachers and the schools; if that doesn't work, you blame the parents; if that doesn't work, you blame the kids because they're just not trying hard enough. An important message for genetics is that you've got to recognize that children are different in their ability to learn. We need to respect those differences because they're genetic. Not that we can’t do anything about it.

It's like obesity. The NHS is thinking about charging people to be fat because, like smoking, they say it's your fault. Weight is not as heritable as height, but it's highly heritable. Maybe 60 percent of the differences in weight are heritable. That doesn't mean you can't do anything about it. If you stop eating, you won't gain weight, but given the normal life in a fast-food culture, with our Stone Age brains that want to eat fat and sugar, it's much harder for some people.

We need to respect the fact that genetic differences are important, not just for body mass index and weight, but also for things like reading disability. I know personally how difficult it is for some children to learn to read. Genetics suggests that we need to have more recognition that children differ genetically, and to respect those differences. My grandson, for example, had a great deal of difficulty learning to read. His parents put a lot of energy into helping him learn to read. We also have a granddaughter who taught herself to read. Both of them now are not just learning to read but reading to learn.

Genetic influence is just influence; it's not deterministic like a single gene. At government levels—I've consulted with the Department for Education—I don't think they're as hostile to genetics as I had feared, they're just ignorant of it. Education just doesn't consider genetics, whereas teachers on the ground can't ignore it. I never get static from them because they know that these children are different when they start. Some just go off on very steep trajectories, while others struggle all the way along the line. When the government sees that, they tend to blame the teachers, the schools, or the parents, or the kids. The teachers know. They're not ignoring this one child. If anything, they're putting more energy into that child.

It's frustrating for Plomin because he knows that eventually DNA mapping will get good enough that real, and helpful, predictions will be possible. We'll be able to target kids early enough to make real differences — earlier than problems actually manifest — and hopefully change the course of their lives for the better. But so far, no dice.

Education is the last backwater of anti-genetic thinking. It's not even anti-genetic. It's as if genetics doesn't even exist. I want to get people in education talking about genetics because the evidence for genetic influence is overwhelming. The things that interest them—learning abilities, cognitive abilities, behavior problems in childhood—are the most heritable things in the behavioral domain. Yet it's like Alice in Wonderland. You go to educational conferences and it's as if genetics does not exist.

I'm wondering about where the DNA revolution will take us. If we are explaining 10 percent of the variance of GCSE scores with a DNA chip, it becomes real. People will begin to use it. It's important that we begin to have this conversation. I'm frustrated at having so little success in convincing people in education of the possibility of genetic influence. It is ignorance as much as it is antagonism.

Here's one call for more reality recognition.

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Still Interested? Check out a book by John Brookman of Edge.org with a curated collection of articles published on genetics.