[MUSIC] So welcome back. I want to talk now about the environment, which is a huge complicating factor in genetics. Huntington's is a disease of the brain which is unfortunately pretty much pure genetic determinism. Your sanity is gonna depend on a short little string of nucleotides. If you inherited the Huntington DNA sequence, it doesn't matter what you do. You can eat an apple every day, you can work out at the gym, nothing's gonna help you, you will eventually lose your mind. But Huntington's is an exception, because involvement doesn't matter with Huntington's. Height is the norm, because like most of our traits, it is multi-factoral and that means the genes and environment work together. So, if I had a pair of twins, and was to feed one twin just chocolates, and the other twin steaks. They wouldn't end up looking alike, would they? So the students at my university, they look like people who've eaten everything they ever wanted to eat. They've reached their full genetic potential for height. Back some years, American soldiers fighting the Japanese, the Koreans, the Vietnamese found out compared to them, Asian soldiers were much smaller. But recent studies on American students show there's no difference in average height at all between young second or third generation American Asians and other Americans. Asians fed an American diet grew as tall as any other Americans, so what does that mean? It means that having minimized the differences in environmental influences, the remaining differences in height are due to genetic differences. 100 years ago, almost all Olympic medals were won by white Europeans and Americans, because only the privileged few had sufficient resources and the chance to train. In an unequal world, background and opportunity determined who won the races. In a true meritocracy with a level playing field, where all have equal opportunity to succeed, the best athletes are gonna be the ones with the best genes cuz that is all that is left to vary. So there's a paradox here. The more equal we make society, the more important we will make the genes. Now traditionally, geneticists used twins to determine the impact of our genes on how we turn out. More than 1.5 million twins around the world take part in studies aiming to assess the relative role of genes and the environment and everything from aging, to disease, from bullying, to religious belief. Now, you probably know that there are two types of twins, these are identical twins here, but there's also fraternal twins. So have a look at this figure. Identical twins, now they're going to develop when a fertilized egg splits into two. So their DNA is going to be identical. Fraternal, or non-identical twins, they're gonna develop in separate eggs and fertilized by separate sperm. So they share only half their genes. So twin studies is just a simple matter of measuring how identical and fraternal twins turn out if separately adopted into different families. You want separate families because environments run in families as well as genes. And you want to separate out the effects of genes and environment. If identical twins separated at both turn out more similar than fraternal twins for a particular trait, hair color, say, then you assume genetic determinism, the genes do the job. If the two types of twins are equally similar for trait, such as the language they speak, then their trait is more likely to be due to the environment. So let's give you a real world example. Among identical twins, if one has epilepsy, then in 59% of cases, so will the other twin. But in fraternal twins if one has epilepsy, then in only 19% of cases will the other twin also have epilepsy. So that's a 40% difference, which indicates a very strong genetic component in epilepsy. Now the end result of twin studies is an estimate of heritability for the trait. Heritability is a slippery little concept. Firstly, you have to understand that heritability is a population average. It does not refer to individuals. If you say that the heritability for height in New York City is 90%, you're saying that 90% of the variation in heights among people in New York City is due to genes, and the remaining 10% of the variation between them is due to their environment. The second thing to understand is the heritability for the trait is gonna vary between populations and environments. Heritability for height in America is going to be very high, because everyone in America is very well-fed. But in a country where starvation stalks the streets, it's gonna be much lower because that will be a factor. Now twin studies in the Western world have shown that almost all traits are in part influenced by genetic differences. Some characteristic,s such as eye color now, show a strong genetic influence because environment doesn't have much impact on what eye color you have. Others, like intelligence, have an intermediate level. Now when heritability is lower, it's usually assumed that selection on the trait is less, because the differences between people are mostly due to their environment. But that's a dangerous assumption. It could actually be because selection has already eliminated genetic variance. So let's explain that using IQ as an example. Now, present studies indicate that the heritability of intelligence, judged largely by IQ scores goes up linearly across lifespan. So from 30% in very young children, to 40%, 50%, 60%, some people even say it becomes 80% heritable by the time you're middle aged. Well that's saying that 80% of the reason that we're all different in IQ is genetic and so it suggests that genes play a majority role in IQ scores. But environment is important, particularly in young people. Now, remember that an average IQ is 100. So potentially the 30% of variation in IQ due to environment could be fairly significant in determining if someone has an IQ of 120, or is in the sub-normal range. However, by the time an adopted child is 18, their IQs correlate with their biological parents, and not their adopted parents. A logical link to this lecture by Mary Wakefield on Robert Province's work, makes the point that the environment, all that mass coaching and tiger mothering can maybe have an effect on the kid's IQ when he's young, bump him up a few notches. But as he gets older, his IQ will become ever more closely correlated with that of his blood relatives. Okay, so with genes having a majority role in how our IQs turn out, does that mean strong counts selection for high IQ? Not necessarily, the habitability of 70% or so implies quite a bit of genetic variation in populations. Otherwise, how could variations in IQ be due to genes? Now in most cases, the effect of selection is to reduce genetic variation. If you remove individuals with a genetic disadvantage, then variation is reduced. We can speculate that low intelligence might be a disadvantage. And if less intelligent people are selected against, their reproductive success is less, then the alleles for low intelligence are gonna be taken out of the population. So for this reason, a low heritability could be an indication that selection has been strong. All the genetic variation has already been selected away and the variation that is left is due to environment. That's the flip side of paradox I mentioned before. If people have a level playing field, level playing field and what's gonna distinguish them is their genes. But if strong selected pressure have already removed most genetic variants, then any differences between people is gonna be due to what's left, in this case, the environment. Whereas, now have a look and see how gene was in twin studies connect up using as an example a study published online in Lancet on 28th February 2013. It's called identification of risk loci with shared effects on five major psychiatric disorders: a genome wide analysis. So if psychiatric illnesses, schizophrenia, bipolar disorder, autism, major depression, and ADHD, they seem very different. Yet some years back researchers had seen clues of overlapping genetic effects in identical twins. One twin might have schizophrenia while the other had bipolar disorder. So researchers had also examined the genes of a few families in which these psychiatric disorders seemed particularly common. They found a few unusual disruptions to chromosomes, so a link to psychiatric illnesses. But what surprised them was that while one person with a mutation might get one disorder, a relation with exactly the same mutation would get a different disorder. So they concluded that two different diagnoses can have the same genetic risk factor. Starting in 2007, a large group of researchers began investigating genetic data generated by studies in 19 countries that allow them to compare 33,332 people with psychiatric illnesses at 27,888 people free of the illnesses. The researchers in their gene study, analyzed scan to these people's DNA, looking for variations in any of several million places along 3 billion DNA letters. The question, did people with psychiatric illnesses tend to have a distinctive DNA pattern in any of those locations when compared to people free of illness? The researchers found that four DNA regions that conferred a small risk of psychiatric disorders. For two of them, it's not clear what genes are involved or what they do. The other two though, involve genes that are part of calcium channels, which are used when neurons send signals in the brain. So let's make it clear, this new study does not mean that the genetics of psychiatric disorders are simple. Researchers say there seem to be hundreds of genes involved, and the gene variation discovered in the new study confer only a small risk of psychiatric disease. So we're just looking, then, at four genetic glitches that can nudge the brain along a path to mental illness. But, what do we make of the fact that the same mutations can have radically different effects on different people? The answer's likely to be that which disease, if any develops is going to depend on multiple other genetic or environmental factors. So, for example, many genes are redundant. By that we mean that if you knock out a gene, break it, one or more other genes might be able to take its place. The particular gene that may be true for you but not for me. I might not have a suitable replacement gene, you might have a suitable replacement gene. Alternatively, you may have a particular allele which could be devastating for you, but it never gets switched on. It switches on in someone else when they confront a stress you are lucky enough to miss out on. Stress is the key word here. You could be fine left alone with your particular alleles until stress comes along and switches those alleles on. Environmental stress has even played a role in the expression of some monogenic diseases, because stresses make them much worse. So for example, patients with the genetic disease cystic fibrosis there's a lot of mucus in the lungs. That's a great breeding ground for the bacteria Pseudomonas. The bacteria causes a lot more coughing and even more mucus, so for many patients with cystic fibrosis, the symptoms of their condition are due to the combined action of the mutation and the stress caused by the bacteria. [SOUND]
