Saturday, June 30, 2012

Summary

Since Gregor Mendel’s discovery of genes of genes in the late 19th century, we have known genes to be the source of inherited traits.  Some of these traits are behavioral as Walter Rothenbuhler found through his study of honey bees.  Technological advancements in molecular biology over the past few decades have allowed us to manipulate specific genes and observe its effect on a particular behavior, allowing us to better understand their relationship.  In this blog series, I shared with you several intriguing discoveries between genes and behavior.  To conclude, in my final blog post, I would like to recap with you these findings.

Circadian Rhythm:  Using the fruit fly, the circadian rhythm, the internal biologic clock that operates on a 24-hour cycle, was found to be controlled by the “period” gene and genes with similar function have been found in the mammal.  Different types of mutations in the “period” gene could have different effect on the circadian rhythm, at times shortening the biological clock and others lengthening it.  Discovery of genes related to the circadian rhythm has allowed us to better understand some human sleeping disorders.
Learning and Memory: Perhaps the most interesting relationship is that between genes and memory as well as learning.  Scientists found that after mutating different genes in the fruit fly, some flies showed difficulty learning or remembering what it has learned.  Flies with a dunce gene mutation were too dumb to learn; flies with a rutabaga gene mutation were unable to form memories; flies with a amnesiac gene mutation were forgetful.  Studies on the mouse also proved that learning or remembering was difficult when an inhibitor which blocked the signals between neurons in the hippocampus was applied.  
Courtship: The courtship behavior is an innate behavior that all animal possess.  The gene that was found to be responsible for the fruit fly’s courtship behavior is the fruitless gene.  Even though male and female fly posses the same fruitless gene, the product of the fruitless gene found be different in sexes (fruF in the female fly and fruM in the male fly).  When scientists switched fruF into fruM, and fruM into fruF, the female fly instead exhibits male courtship behavior toward female flies, and the male fly exhibit an abnormal courtship behavior toward male flies.
Aggression:  Aggression is an innate behavior that is vital to self-preservation.  Studies found that the fruitless gene in the fruit fly also affects its aggressive behavior.  Similar to the fruit fly’s courtship behavior, after switching fruitless gene’s product in the two sexes, the female fruit fly exhibits male aggressive behavior, boxing and lunging, and the male fly exhibits female aggressive behavior, shoving and head-butting.  Furthermore, by using genetically altered mice, scientists were able to activate the mouse’s aggressive behavior simply by turning on a blue light, which would make the mouse attack furiously. 

A myriad of human studies have been carried out and the findings have raised many voices in society.  For instance, the discovery of the “warrior gene”, which is the MAOA gene, is thought to be highly related to human aggressive behavior.  People that were found to posses the warrior gene often exhibit violent behavior such as joining a gang or committing a crime.  Scientists also found “gay gene” (xq28 region), Schizophrenia gene, or a gene (AVPR1A) to be associated with monogamy.  Nature versus nurture theories have long been debated.  Many people now believe that our genetic makeup does not dictate our behaviors, but instead, our behaviors are products of our genes and the environment we encounter throughout our life.

Tuesday, June 26, 2012

Aggression

People usually avoid going near a hissing cat or a teeth-baring dog because we know that those animals are showing aggression and would likely attack anything that comes near them.  Aggression, in its broadest sense, is behavior that is forceful, hostile, or attacking.  It may occur either in retaliation or without provocation.  In narrower definitions that are used in social sciences and behavioral sciences, aggression is an intention to cause harm or an act intended to increase relative social dominance.  Even though aggression behaviors appear to only cause hazard, it is a self-preservation skill that is vital for animals to survive in the world. 
Every animal, even animals as small as fruit fly, has a unique set of behaviors to show aggression.  Male and female fruit flies express different styles of aggression.  Male flies express a boxer-like aggression.  Specifically, they wrestle with each other (See video1), and lunge their razor sharp foreleg to attack their opponent’s back (See video2).  Female flies, on the other hand, express a less violent behavior.  Instead of boxing and lunging like male flies, female flies’ exhibited aggression by shoving and head-butting.  In my previous blog post, I showed that male and female fly’s courtship behavior switches when scientists switch the fru gene.  Here, scientists also found that by switching the fru gene, male and female fly’s aggression behavior had also switched.  (Nilsen, et al., 2004)  In other words, when male flies express fruF, their display of aggression became shoving and head-butting, and when female flies express fruM, they exhibited boxing and lunging.  Even though the reason for this behavior switch between sexes is still unclear, scientists were sure that there is a gene for controlling aggression behavior as well.  (Side note: Though scientists have established the importance of the fruitless gene, you may find it strange that it has been implicated in both aggression and courtship behaviors.  I suspect that its true role is that of sex identification as a switch of the gene in males and females seem to disrupt their ability to display sex-appropriate behaviors.)
Once the scientists were certain a genetic link to aggression scientists began to study it in a more complex organism the mouse.  Mammals like the mouse, not only have many more genes than the fruit fly, their genetic system is also much more complex  Consequently, specific genes related to aggression have yet to be identified.  However, scientists have discover a specific region in the brain highly related to the control of aggression.
In order to manipulate the mouse’s aggression, scientists genetically engineered the neurons of the “aggression center” to be activated by a blue light rays  The results were astonishing.  Scientists found that whenever the blue light was turned on, the mouse would start attacking and would stop its attack whenever the blue light is off.  (See video below, Liu, et al., 2011)

The discovery of the link between genetics and aggression has raised great concern and sparked debate in our society.  Some people have gone so far as to claim that our genes are to blame for aggressive behaviors, including criminal acts such as murder.  As much as some people believe that we are influenced by the genes we are born with, scientists have also found that most biologic mechanisms are molded by our environment.

Sunday, June 24, 2012

Courtship

Previews studies have shown that genes control a myriad of behaviors.  Even complex behaviors such as learning are controlled by genes.  It was not a surprise when scientists found a gene which controls courtship behavior.  Courtship display is a special, sometimes ritualized, set of behaviors which some animals perform as part of courtship.  Courtship behaviors can include special calls, postures, and movements, and may involve special plumage, bright colors, or other ornamentation.  Courtship is a vital behavior that facilitates a species’ ability to procreate and pass along its genes to the next generation.  A mutation in the gene that controls the courtship behavior, would greatly affect the animal’s courtship behavior and endanger the species’ survival in the world. 
Fruit flies have been used as a primary animal model for the study of the genetics behind courtship display due to its very distinct nature.  First, the male fly orients itself towards the female fly.  Next, the male fly starts tapping its foreleg on the female fly and  vibrating its wing (which is perceived as singing) to the female fly.  Last, the male fly licks the female fly and then attempts copulation.   (See figure below)
However, when a specific gene is mutated, the fruit flies’ courtship display content and their targets change.  Scientists named this courtship controlling gene fruitless, fru.  There are two forms of proteins from the fru gene - fruM, which is only produced in the male fly, and fruF, which is only produced in the female fly.  A series of experiments demonstrated the importance of these genes in courtship behavior.  When fruM is replaced by fruF, the male fly displays its courtship behavior towards a male instead of a female.  These fruF–expressing male fly also display an bizarre and unnatural behavior called chaining during which all mutated male fly follow each other in a line.  (See video).  Scientists also found that when fruM is expressed in the female fly, the female fly displays male courtship behavior towards another female fly.  (Stockinger, et at., 2005)  Reasons for these mutated flies to display lose differentiation between sexes are still unknown.  The effect of the fruitless gene on the fruit fly’s courtship behavior, however, is conspicuous.
Human courtship behaviors are more complex and less distinct.  Therefore, pinpointing a gene that changes our behaviors is far more difficult.  Nonetheless, a molecular geneticist of the National Cancer Institute, Dean Hamer, caused a great stir in the scientific community.  In 1993, he discovered a certain region (which Hamer named Xq28) on one of the X chromosomes (that is, the chromosomes passed from a mother to a son) was 82% similar to brothers who were both identified as homosexual.  However, no conclusion has been drawn from this study because no one has been able to duplicate Hamer’s study.  Furthermore, a similar experiment that was conducted by George Ebers (a neurogenetecist in the University of Western Ontario), showed that the Xq28 region was not consistently shared by homosexual brothers, contradicting Hamer study.
Nature versus nurture theories have long been debated.  Most would agree that our behaviors, possibly including courtship behavior and sexual orientation, are likely a product of both innate character (i.e. our genetic makeup) as well as influences of our environment.  Continued research on the relationship between genes and behavior will further our understanding of the essence of what makes us who we are.

Tuesday, June 19, 2012

Learning and Memory

Animals begin to learn as soon as they are born.  Horses learn to stand within seconds and to walk within minutes of birth.  Birds learn to migrate and wolves learn their social status within their group.  Learning is a complex innate behavior which is likely controlled by a myriad of genes.  While there is an abundance of information to study, the complexity of the genetic processes behind learning effectively forbids practical research. Therefore, scientists instead focus research on a simpler, but highly related process – memory formation.
Memory formation and learning are two closely linked processes.  It would be impossible to learn without forming new memories.  Memories are thought to be stored by neurons (the building blocks of the brain) located in the hippocampus.  The link between memory and the hippocampus was discovered after observing that patients who had suffered injury to the hippocampus were no longer able to form new memories.
Patients preparing for brain surgery will undergo a procedure called brain-mapping, a process in which electrodes are inserted into the brain to identify regions with vital functions to ensure their preservation during surgery.  Taking advantage of the brain-mapping procedure, scientists have been able to conduct some intriguing studies.  After patients have electrodes (which can be placed with such precision so that it records activity from a single neuron) inserted into the hippocampus, they are shown pictures of random subjects  The patients are asked whether they recognized the subject in each picture.  This study demonstrated that each memory neuron becomes activated in response to a very specific subject.  For instant, a neuron in one of the patients only responded to a picture of Jennifer Aniston.  Another memory cell from a different patient only responded to a picture of Halle Berry.  Moreover, a sketch of the actress, or a string of words contaning her name also triggered its response.  [Quiroga, et al., 2005]. 
Scientists have discovered several genes that affect learning through animal studies.  In one study, fruit flies were trained to associate a specific odor to an electric shock.  This training was done by giving the flies an electric shock whenever the specific odor was presented in a tube.  A trained fruit fly would avoid the tube that contained the specific odor but three types of mutant genes were unable to learn to avoid the odor, which they named -– dunce (too dumb), rutabaga (unable to form memories) and amnesiac (forgetful)  A similar experiment was performed on mice, but instead of mutating genes, scientists used an inhibitor to block signaling between neurons.  This experiment had the same outcome as the fruit flies.  The mice were unable avoid electric shock in the presence of a neuron inhibitor (see video below).  [Pastalkova, et al., 2006]
We are only beginning to understand the mechanisms behind complex behaviors such as learning.  We believe these mechanisms are intricately controlled by a series of genes.  How fascinating is it that a defect in just one gene can entirely disrupt learning!

Sunday, June 17, 2012

The Circadian Rhythm

Behavior is highly related to genes.  The most effective way to find the genes controlling behavior is to study the most instinctive and basic behaviors, because those genes are the most conserved, meaning the gene is present not only in every human, but also in most other species.
 There are many things we do on a daily basis that we take for granted.  We wake up and go to sleep on a twenty-four hour cycle, most of us at roughly the same time of day, everyday.  We may not realize this is actually one of our instinctive behaviors until we travel to different time zones.  Anyone who has traveled to a different time zone has experienced jet-lag, which can cause you to feel wide awake in the middle of the night, hungry at odd hours of the day.  This is actually caused by our internal clock - the circadian rhythm.  (See figure below for human circadian rhythm)

The circadian rhythm has been widely observed in plants, animals, and even fungi.  The circadian rhythm is basically the internal clock that dictates cyclic biological processes, such as sleep and hunger.  In order to better understand circadian rhythm, scientists started their studies on an animal with fewer genes, the fruit fly. 
Scientists were able to identify the key gene that dictates circadian rhythm through creating a fly that behaved oddly (i.e. it was active and slept during odd hours).  They did so by creating random mutations in almost every possible gene and observing the resultant behavior.  Eventually, they identified a gene they named “Period”, or “per”.  Among the fruit flies, scientists found four different types of the per gene: per, per0, pers, and perL.  The flies that contained the per gene had a normal activity cycle, a twenty-four hour time period; the flies that contained the per0 gene had a random activity cycle, a time period that could not be determined; the flies that contained the pers gene had a shorter activity cycle, a nineteen-hour time period; the flies that contained the perL had a longer activity cycle, a twenty-nine hour time period.  [Konopka & Benzer, 1971]
After the discovery of the per gene, scientists wondered if the gene exists in mice, which are mammalian and nocturnal (active at night), and if a mutation in the per gene has an effect on the mice’s circadian rhythm.  The answer is “yes”.  However, mammals are more complex than fruit flies.  Scientists not only found more than one type of “per”, but they also found other genes that affect the circadian rhythm
The discovery of the per gene has not only shed light on our understanding of our sleeping behavior, but also helped us to find the cause of some sleeping disorders, such as the “Familial Advanced Sleep Phase Syndrome (FASPS)”, found to be due to a mutation in the human “Period2 (Per2)” gene.  It is interesting that something which comes so naturally to us is actually controlled by an intricate genetic network.

Tuesday, June 12, 2012

Do genes really control behavior?

In my previous blog entry, I gave examples that made people wonder whether genes are responsible for an animal’s or our own behavior.  This idea was further enhanced by an important discovery in 1964.
Walter C. Rothenbuhler was an American Zoologist that studied honey bees and observed interesting behaviors among these honey bees.  He made his discoveries when he was tasked to breed a new line of honey bees with both a high survival rate and honey production.  He focused on two different species of honey bees - the “Brown” line and the “Van Scoy” line.  The Brown honey bees, which he defined as hygienic, will uncap the lid from a comb of brood and remove the larvae inside if they  found them infected.  The Van Scoy honey bees (non-hygienic), on the other hand, will not.  This cleansing behavior of the Brown honey bees greatly increases their colony survival rate, which was proven when Rothenbuhler manually infected a portion of the two colonies’ larvae.  However, the Van Scoy honey bees produce more honey than the Brown honey bees.  (Picture below shows how Rothenbuhler manually infects the larva) 
 
In his attempts to create a honey bee that had both high survival rates as well as high honey production, Rothenbuhler cross-bred the two line of bees.  After many generations of breeding, he discovered four different kinds of behavior among various lines of these offspring.  Two of these lines behaved similarly to their parents - hygienic like the Brown bees and non-hygienic like the Van Scoy bees.  However, the other two types of bee lines exhibited entirely different kinds of behavior.  One of them, named “uncappers”, would only uncap the lid of the comb but would not remove the infected larva inside.  The other ones, named “removers”, seems to behaved the same way as the Van Scoy bees (non-hygienic but when Rothenbuhler uncapped the lids of the combs manually, the removers would go inside the comb and remove the infected larva.
Those who are familiar with genetics would know that this cross-breeding technique is the fundamental way of breeding a line with the specific gene responsible for a specific phenotype (an observable characteristic or trait of an organism).  Even though this technique can be dated back to Gregor Johann Mendel, the "father of modern genetics" and discoverer of the “laws of Mendelian inheritance”, of the 19th century, it is still widely used in many labs throughout the world today.
Prior to the discovery of techniques to study molecular biology, scientists were unable to isolate and identify the specific genes that were responsible for certain types of phenotypic behavior.  However, thanks to rapid developments in the world of molecular biology over the half-century, scientists today are able to not only isolate and identify genes of interest ,but also further manipulate those genes and observe the resultant behaviors in an animal. 
Without a doubt, genes do play a role in animal, and likely human, behavior.  What is still widely debated is how far does this phenomenon go?  How specific?  Are genes the entire fabric of our nature and dictate all our actions?  Or are genes only the first step in a series of reactions?  Will a mutation in a specific gene cause a dramatic change in certain behavior?  Through continued research, scientists have begun to shed light on these interesting questions.  (To be continued…)

Sunday, June 10, 2012

What controls our behavior?

Behavior is the way a person or an animal reacts to a stimulus from the environment.  A specific type of behavior occur in response to a specific type of stimulus.  For instance, a dog would not wag its tail at and a cat would not purr to a threatening subject.  Since Ancient Mesopotamian and Ancient Egyptian times, people have known that the brain controls one’s behavior.  The brain’s connection to human behavior was increasingly understood after observing behavioral change in subjects who had suffered brain injury.  The most famous and described case of behavior change after brain injury was the case of Phineas P. Gage of the 19th century.  (Picture below shows Gage holding the iron rod that went through his head)

Gage was an American railroad construction foremen, who survived an accident in which a large iron rod went through his head and destroyed most of his left frontal lobe.  Before the accident, Gage was described as a hard-working, responsible, and "a great favorite" with the men in his charge.  His employers had regarded him as "the most efficient and capable” foreman” in their employment.  However, after the accident, his personality changed drastically.  “He is fitful, irreverent, indulging at times in the grossest profanity, manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times pertinacious obstinate, yet capricious and vacillating, devising many plans of future operation, which are no sooner arranged than they are abandoned in turn for others appearing more feasible”, described by Dr. John Martyn Harlow.
Another example was the lobotomy, which was a radical physical therapy for the asylum's patients in the first half of the 20th century.  This psychosurgery cuts the connections to and from the prefrontal cortex, located in the front portion of the brain.  After lobotomy, patients’ behaviors changed dramatically and it appeared as if they were no longer plagued by their “insanity”.  This behavioral change led psychiatrists to believe that "prefrontal lobotomy reduces anxiety feelings and introspective activities; feelings of inadequacy and self-consciousness are thereby lessened.  Lobotomy reduces the emotional tension associated with hallucinations and does away with the catatonic state", as described in the Psychiatric Dictionary in 1970.  It is now known that, in fact, the prefrontal cortex is responsible for the orchestration of thoughts and the actions in accordance with internal goals.
If the brain controls behavior, it begs the question, what then controls the brain?  Scientists have long wondered, whether a person’s genetic makeup dictates behavior.  The relationship between genes and behavior was first investigated through the study of patients with schizophrenia, which is considered as a more complex “behavior”, and their family members.  It was observed that among the family members of a schizophrenic, his or her identical twin (monozygotic twin), who shares the same exact genetic makeup, had the highest risk of developing schizophrenia.  This observation was also made for more complex behaviors such as memory, neuroticism, vocational interests (adolescence), extraversion, spatial reasoning, scholastic achievement(adolescence), processing speed, verbal reasoning, and general intelligence.  [Plomin, et al.,1994].  These twin studies suggest that genes are at least in part, responsible for our behaviors.  Today’s research focuses on the direct relationship between genes and behavior.