Professor Sapolsky begins by recapping the material from the prior lecture. DNA as the big boss man is undermined as we learn that 95% of the DNA is simply the instruction manual, that transcription factors have huge roles especially in an if-then manner, that splicing and epigenetic effects impact growth, and on and on. Here he highlights ways in which things are interconnected - environment, genes, etc. In this area we move toward a way of thinking that seems to interest Sapolsky - the whole chaos theory/Heisenberg Uncertainty Principle element of life in which there's a bit of randomness and chance in even the most structured systems. And yet there's also a bit of structure in the seemingly chaotic. This just might be an important theme in evolution...
As promoters change, transcription factors change. Splicing enzymes can change their behavior and create entirely new proteins. Changes in transcription factors can activate entirely different gene sequences. Little changes can have big results, especially when those changes cascade.
Vasopressin and vols (and perhaps humans). One version of the promoter stimulates release of more vasopressin. Correlated with this is an increase in monogamous mating. The more vasopressin, the more likely the vol is to be monogamous. And polygamous vols, when given vasopressin, begin behaving monogamously. There's some evidence that this impacts human behavior too. Sapolsky mentions a study that suggested that the type of vasopressin promoter you have provided some predictive power of the likelihood of you getting divorced down the line. Naturally there are three million confounds here, but it gives one pause in terms of the concept of free will.
Dinorphin (pain receptor) promoters seem to relate to ease of addiction to pain killing drugs in rats. The more promoters that the rat has for dinorphin, the more likely that rat is to exhibit addictive behavior toward pain killing drugs when given the opportunity.
Changing transcription factors changes gene networks. He notes that a disproportionate share of the differences in the genetic code between chimps and humans lie in the genes that code for transcription factors. This leads to the suggestion that the most interesting evolutionary changes are going to be those found in changes in the regulatory structure of the genes, not in changes to the DNA itself.
The more genes you find in a species, the greater the percentage of those genes that code for transcription factors. For example you have 1 gene, A, so there's 1 transcription factor. Have two genes, A and B, and you now have 3 transcription factors - one for A, one for B and one for AB. And so on down the line.
Microevolution is about the proteins; macroevolution is about the networks.
Next he introduces one of his favorite biologists, a plant geneticist named Margaret McClintock. He goes through a history of one of her experiments in which she argued for transposable genes in plants, i.e. genes that are actually moving around on the DNA line, creating new proteins, networks, results. This amazing feature is also seen in the human immune system which adapts itself constantly in order to combat pathogenic invaders (and sometimes, unfortunately, to combat things like the insulin production cells in the Islets of Langerhorn - giving the person Type I diabetes). A plant can't run away from trouble, so it had to evolve another way to handle the world's difficulties. So they have fancy stress response tricks, such as changing genes around to handle new environments and challenges.
This is done by activating transposaze, which is a splicing enzyme that slices out sections of the genes so they can jump around. These types of genes are also seen in animals.
Predictably, and unfortunately, pathogens also get to utilize this trick. Trypanosoma brucei is a nasty protazoan that causes sleeping sickness in humans. It invade the body and in order to evade the host's immune response, uses jumping genes to change its protein coating. So the adaptive immune system stays a step behind it because just as soon as it figures out how to kill the original coating, the trypanosoma has changed its shield. The adaptive immune system takes out pathogens in a sort of lock and key function, but if the pathogen changes the locks faster than the immune system can chisel out the keys, you're in for real trouble.
This phenomenon is known as antigenic variation. In essence the pathogen has numerous shells (for this parasite the estimate is in the thousands) and shuffles through them as it replicates itself. It puts the immune system at a distinct disadvantage. Imagine you're a detective and you can only catch your suspect if he's wearing the exact same outfit he had on when he committed the crime. If he has 1 shirt, 1 pair of pants and one pair of shoes, you'll catch him immediately. If he has 1 shirt, 1 pair of pants and 2 shoes, it's going to take 2 days. If he has 15 shirts, 15 pairs of pants and 5 shoes, you're eating donuts, drinking coffee and peeing in a Mountain Dew bottle for 1,125 days. If the suspect is there to rob 25 liquor stores and 10 banks while you look for outfit #1, he's got a lot of time to get it done.
This happens elsewhere in the body. Neuroprogenitor cells can also jump around - this is neurons moving around, this is the cells in your body that have the most to do with determining who you are being the least constrained by genetic determinism.
So a hormone has the two receptors on it - one on the hormone side to trigger it and other that connects to the promoter. These can be mixed and matched so that a hormone can be triggered and then go out and attach to an entirely new promoter. This is a new if-then clause.
Glucocorticoids are stress hormones that suppress the immune system (there's a lot more to it, but in brief, they suppress it by reducing the inflammatory response). A slight clip and a little shuffling and you can create the new if-then clause if there's progesterone around suppress immunity. What's this about? Pregnancy. This if-then statement prevents the immune system from attacking the fetus.
The downside is that when the immune system recovers, it sometimes overshoots the original mark and ends up getting hyper. In its hyper state it's over-reactive and next thing you know you have an auto-immune disease, which is more common after pregnancy. This can be dangerous and some autoimmune disorders, such as lupus, are severe enough that the affected will be advised to avoid pregnancy.
Next up are copy number variants. This is the world of multiple copies of the same gene. This can allow for experimentation with one back-up copy. At the same time, there can be problems linked to it, such as is seen with schizophrenia. The multiple copies of genes may account for "irreducible complexity," i.e. how can an eye pop up out of nowhere? If the organism has multiple copies of sensory genes and is able to experiment with one without sacrificing the other, it could develop a feature incrementally, slowly growing an eye while using sound and tactile information for guidance until such time as the eye starts working. (This can account for evolution's production of vision while leaving a very big door open in regard to what's out there that we haven't evolved to see. This is the whole world of intuition and spiritual belief. This is the whole world of wackos that claim they can sense things others can't. Or is it?)
For the most part these changes will not be beneficial overall since they have to coordinate with so many different gene networks. Therefore it's generally a stabilizing selection in which you won't see much change. However, when the genes stumble onto something good, you may see a rapid change.
Bottlenecks occur when particular traits enable a subset of the population to survive, regardless of the problems with their other traits. He states cheetahs went through this. Sickle cell anemia is another common example.
Sapolsky moves on to talk about insulin resistance. In brief, the hominid body is designed to store nutrients. These days our food is loaded with all kinds of everything. So we're seeing a huge increase in average body mass (folks are getting fatter) because the body is storing all the good and bad stuff. The more wasteful your metabolism, the better it is. Get yourself a body that isn't used to a western diet and you are a candidate for type II diabetes as your body grows beyond what it's supposed to. The fat cells get full and start ignoring insulin. Insulin gets angry and calls on the pancreas to make more insulin to help force the fat cells to do their job. The fat cells relent a little but demand ever greater amount of insulin to listen and pretty soon you've got a blood sugar problem and are well on your way to burning out your pancreas.
The Dutch Hunger winter is a great example of this. Due to Nazi shuffling of food, the Dutch experienced a winter of starvation. The women who were carrying babies gave birth to "thrifty" babies whose metabolisms had learned to hold tightly onto whatever nutrients floated by. Thus they are more at risk for all the metabolic problems in adulthood - hypertension, diabetes, excessive weight gain, etc. And so are their offspring since they gestated within a mother's body that was very thrifty and thus shared less nutrients.
Sometimes there are surprising effects from genetic variation, such as the story of the silverfox.
As promoters change, transcription factors change. Splicing enzymes can change their behavior and create entirely new proteins. Changes in transcription factors can activate entirely different gene sequences. Little changes can have big results, especially when those changes cascade.
Vasopressin and vols (and perhaps humans). One version of the promoter stimulates release of more vasopressin. Correlated with this is an increase in monogamous mating. The more vasopressin, the more likely the vol is to be monogamous. And polygamous vols, when given vasopressin, begin behaving monogamously. There's some evidence that this impacts human behavior too. Sapolsky mentions a study that suggested that the type of vasopressin promoter you have provided some predictive power of the likelihood of you getting divorced down the line. Naturally there are three million confounds here, but it gives one pause in terms of the concept of free will.
Dinorphin (pain receptor) promoters seem to relate to ease of addiction to pain killing drugs in rats. The more promoters that the rat has for dinorphin, the more likely that rat is to exhibit addictive behavior toward pain killing drugs when given the opportunity.
Changing transcription factors changes gene networks. He notes that a disproportionate share of the differences in the genetic code between chimps and humans lie in the genes that code for transcription factors. This leads to the suggestion that the most interesting evolutionary changes are going to be those found in changes in the regulatory structure of the genes, not in changes to the DNA itself.
The more genes you find in a species, the greater the percentage of those genes that code for transcription factors. For example you have 1 gene, A, so there's 1 transcription factor. Have two genes, A and B, and you now have 3 transcription factors - one for A, one for B and one for AB. And so on down the line.
Microevolution is about the proteins; macroevolution is about the networks.
Next he introduces one of his favorite biologists, a plant geneticist named Margaret McClintock. He goes through a history of one of her experiments in which she argued for transposable genes in plants, i.e. genes that are actually moving around on the DNA line, creating new proteins, networks, results. This amazing feature is also seen in the human immune system which adapts itself constantly in order to combat pathogenic invaders (and sometimes, unfortunately, to combat things like the insulin production cells in the Islets of Langerhorn - giving the person Type I diabetes). A plant can't run away from trouble, so it had to evolve another way to handle the world's difficulties. So they have fancy stress response tricks, such as changing genes around to handle new environments and challenges.
This is done by activating transposaze, which is a splicing enzyme that slices out sections of the genes so they can jump around. These types of genes are also seen in animals.
Predictably, and unfortunately, pathogens also get to utilize this trick. Trypanosoma brucei is a nasty protazoan that causes sleeping sickness in humans. It invade the body and in order to evade the host's immune response, uses jumping genes to change its protein coating. So the adaptive immune system stays a step behind it because just as soon as it figures out how to kill the original coating, the trypanosoma has changed its shield. The adaptive immune system takes out pathogens in a sort of lock and key function, but if the pathogen changes the locks faster than the immune system can chisel out the keys, you're in for real trouble.
This phenomenon is known as antigenic variation. In essence the pathogen has numerous shells (for this parasite the estimate is in the thousands) and shuffles through them as it replicates itself. It puts the immune system at a distinct disadvantage. Imagine you're a detective and you can only catch your suspect if he's wearing the exact same outfit he had on when he committed the crime. If he has 1 shirt, 1 pair of pants and one pair of shoes, you'll catch him immediately. If he has 1 shirt, 1 pair of pants and 2 shoes, it's going to take 2 days. If he has 15 shirts, 15 pairs of pants and 5 shoes, you're eating donuts, drinking coffee and peeing in a Mountain Dew bottle for 1,125 days. If the suspect is there to rob 25 liquor stores and 10 banks while you look for outfit #1, he's got a lot of time to get it done.
This happens elsewhere in the body. Neuroprogenitor cells can also jump around - this is neurons moving around, this is the cells in your body that have the most to do with determining who you are being the least constrained by genetic determinism.
So a hormone has the two receptors on it - one on the hormone side to trigger it and other that connects to the promoter. These can be mixed and matched so that a hormone can be triggered and then go out and attach to an entirely new promoter. This is a new if-then clause.
Glucocorticoids are stress hormones that suppress the immune system (there's a lot more to it, but in brief, they suppress it by reducing the inflammatory response). A slight clip and a little shuffling and you can create the new if-then clause if there's progesterone around suppress immunity. What's this about? Pregnancy. This if-then statement prevents the immune system from attacking the fetus.
The downside is that when the immune system recovers, it sometimes overshoots the original mark and ends up getting hyper. In its hyper state it's over-reactive and next thing you know you have an auto-immune disease, which is more common after pregnancy. This can be dangerous and some autoimmune disorders, such as lupus, are severe enough that the affected will be advised to avoid pregnancy.
Next up are copy number variants. This is the world of multiple copies of the same gene. This can allow for experimentation with one back-up copy. At the same time, there can be problems linked to it, such as is seen with schizophrenia. The multiple copies of genes may account for "irreducible complexity," i.e. how can an eye pop up out of nowhere? If the organism has multiple copies of sensory genes and is able to experiment with one without sacrificing the other, it could develop a feature incrementally, slowly growing an eye while using sound and tactile information for guidance until such time as the eye starts working. (This can account for evolution's production of vision while leaving a very big door open in regard to what's out there that we haven't evolved to see. This is the whole world of intuition and spiritual belief. This is the whole world of wackos that claim they can sense things others can't. Or is it?)
For the most part these changes will not be beneficial overall since they have to coordinate with so many different gene networks. Therefore it's generally a stabilizing selection in which you won't see much change. However, when the genes stumble onto something good, you may see a rapid change.
Bottlenecks occur when particular traits enable a subset of the population to survive, regardless of the problems with their other traits. He states cheetahs went through this. Sickle cell anemia is another common example.
Sapolsky moves on to talk about insulin resistance. In brief, the hominid body is designed to store nutrients. These days our food is loaded with all kinds of everything. So we're seeing a huge increase in average body mass (folks are getting fatter) because the body is storing all the good and bad stuff. The more wasteful your metabolism, the better it is. Get yourself a body that isn't used to a western diet and you are a candidate for type II diabetes as your body grows beyond what it's supposed to. The fat cells get full and start ignoring insulin. Insulin gets angry and calls on the pancreas to make more insulin to help force the fat cells to do their job. The fat cells relent a little but demand ever greater amount of insulin to listen and pretty soon you've got a blood sugar problem and are well on your way to burning out your pancreas.
The Dutch Hunger winter is a great example of this. Due to Nazi shuffling of food, the Dutch experienced a winter of starvation. The women who were carrying babies gave birth to "thrifty" babies whose metabolisms had learned to hold tightly onto whatever nutrients floated by. Thus they are more at risk for all the metabolic problems in adulthood - hypertension, diabetes, excessive weight gain, etc. And so are their offspring since they gestated within a mother's body that was very thrifty and thus shared less nutrients.
Sometimes there are surprising effects from genetic variation, such as the story of the silverfox.
The last fear is that of antibiotic resistance. MRSA, VRE, smallpox, our friend trypanosoma, all with a capacity to evolve faster than our drugs. So there's a continual battle between the cells of our body and the pathogens that want to crash the party.
