Recently during our lab journal club, BP briefly discussed an interesting article came up in science. It reported the discovery of the gene for an extended phenotype (Hoover et al, Science (333) 2011). Extended phenotype is a concept first proposed by Dr. Richard Dawkins. The accepted notion is that gene codes for proteins which determines the phenotype (with lots of exceptions..). But Dawkins proposed that when we describe phenotype it should also encompass the effect that gene has on the environment surrounding the organism, mostly through its influence on the behaviour of the organism.
For example, there is a disease in European gypsy moth called 'tree top disease'. It is a condition caused by a type of virus called baculovirus ( and you are going to hate me when I spell out its zoological name: Lymantria dispar nucleopolyhedro virus. my apologies!). A normal moth hide in crevices or soil during day time to avoid predators and climb back to leaves during night to feed. In contrast, the virus infected moth climb to tree top to die!! Its body then get disintegrated and release millions of viral particle, resulting in a viral shower which infect other caterpillars at the bottom of the tree. So the virus somehow manipulate the behaviour of the moth to aid in its own propogation. If a particular gene product in the virus is causing this behavioral change in moth it will be a very good example of an extended phenotype, because the gene product in virus is causing a behavioural change in its host. And thats exactly what they got! In this case the gene was found to be ecdysteroid (egt) which inactivate the molting hormone in the moth. When scientists infected the moth with virus with no 'egt' the moth did not climb to tree top. Whereas, the moth was infected with virus containing a noram copy of egt gene the moth showed all the symptoms of the disease. Thus egt gene in the baculo virus caused the behavioural modulation of its host. The first gene identified of its kind.
But the phenomenon where a parasite modifying the behaviour of the host is nothing new to biologists. One case with particular interest for humans is Toxoplasma gondii. Its a protozoan parasite with cat as its primary host. A wide variety of warm blooded animals can act as secondary hosts (including but not limited to humans and rodents). The sexual reproduction take place in cats. In other organisms it exist by forming a cyst mostly
in muscles and brain. The reason why we are discussing about it is due to its impact on infected rodent's behavior. Rodents, rat or mice for example, has an innate fear for cats, their natural predator. It is an evolutionarily conserved behaviour. Mice which are bred in laboratory for 100's of generations would still have this fear (ie an animal by himself or any of its bygone ancestors have never had to encounter a cat or its smell). If you expose one such animal to cat urine they show all signs of fear and they avoid that area. Whereas a toxoplasma infected rat do not show any sign of fear, infact they seems to be attracted to the cat smell. To be precise, the uninfected rats when exposed to cats urine showed neuronal activity in the 'defensive part of brain (ventromedial hypothalamus) whereas in a Toxoplama infected mice the same stimuli increased the neuronal activity in the reproductive part (posterodorsal medial amygdala) of the brain. ie, to a Toxoplasma infected rat, its arch nemesis cat will look like a potential sexual partner! Is there any creepy way to make yourself a lunch! And with this the Toxoplasma achieve its goal of getting into its primary host (cat). What an ingenious idea! I found a very informative video on the description of these findings and related ideas by Dr. Robert Sapolsky @ http://edge.org/3rd_culture/sapolsky09/sapolsky09_index.html.
in muscles and brain. The reason why we are discussing about it is due to its impact on infected rodent's behavior. Rodents, rat or mice for example, has an innate fear for cats, their natural predator. It is an evolutionarily conserved behaviour. Mice which are bred in laboratory for 100's of generations would still have this fear (ie an animal by himself or any of its bygone ancestors have never had to encounter a cat or its smell). If you expose one such animal to cat urine they show all signs of fear and they avoid that area. Whereas a toxoplasma infected rat do not show any sign of fear, infact they seems to be attracted to the cat smell. To be precise, the uninfected rats when exposed to cats urine showed neuronal activity in the 'defensive part of brain (ventromedial hypothalamus) whereas in a Toxoplama infected mice the same stimuli increased the neuronal activity in the reproductive part (posterodorsal medial amygdala) of the brain. ie, to a Toxoplasma infected rat, its arch nemesis cat will look like a potential sexual partner! Is there any creepy way to make yourself a lunch! And with this the Toxoplasma achieve its goal of getting into its primary host (cat). What an ingenious idea! I found a very informative video on the description of these findings and related ideas by Dr. Robert Sapolsky @ http://edge.org/3rd_culture/sapolsky09/sapolsky09_index.html. Interestingly, study conducted in Glenn McConkey's lab (Leeds University, London) showed that Toxoplasma genome has two genes that code for Tyrosine hydroxylase, that produces L-Dopa (precursor of a neurotransmitter dopamine). Dopamine stimulates lots of neural circuitry corresponding reward pathway, pleasure seeking behaviors etc. The hypothesis is that Toxoplasma hijacks the brain circuit of mice and makes it act in a crazy manner. Studies have also shown an increasing concentration of dopamine in the limbic system (a part of brain responsible for emotional reaction, among many other things) of mice infected with the parasite. There are key experiments to do, like infecting mice with Toxoplasma with deletion of Tyrosine hydroxylase to test whether the animals behave normally. Another interesting question is how does this parasite the override the fear response of the mice (getting it ready for "dying for sex!). Well, then the obvious question is does it have any similar impact on human infected with Toxoplasma. In an individual with healthy immune system, Toxoplasma do not cause any major symptoms. But it can cause fatal damge to foetus (which do not have its own immune system developed) and also in patients with defective immune system (Eg. AIDS). Recently there are number of studies showing increased incidence of Schizophrenia in toxoplasma infected patients (again increased dopamine is one of the alteration seen in schrizphrenic brain!). Is there a causal link there? Too early to say.
In nature there are several interesting examples of mind bending parasites. Thers is one wasp which attack this poor caterpillar. It will not kill the caterpillar, but instead lay egg in it. After a couple of weeks the eggs would hatch and larvae would come out and form pupae. The fate of the caterpillar is very different. It will turn into a 'zombie bodyguard'. The caterpillar will stop eating, immobile and stays near the pupae. All it does it bang is head violently when a bug, which predates on the pupae (and caterpillar itself) comes nearby. By this it scares away the the bug and save the pupae. Eventually the pupae would transmogrify into wasp and would fly away; but the caterpillar would die away. Thus the wasp some how turns the caterpillar into not only an incubator for its eggs, but also a body guard for its offsprings.
Well, we are talking only about caterpillars and bugs (except weak links between human behaviour and Toxoplasma). But seriously, are there bugs in our brains too which makes us think and act differently from each other? We know about rabies virus turn unfortunate individuals to act violently. There are reports of gut bacteria altering the eating patten of humans (a whole separate story by itself!). Are we all the "extendend phenotype" of some virus surreptiotiously trying to perpetuate its nucleir acid codes hidden in our genome? I am not confident to say an absolute NO.
Picture courtesy: http://en.wikipedia.org/wiki/File:Toxoplasmosis_life_cycle_en.svg
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