Genes Teach Us About Parkinson's Disease, Part 1

Parkinson’s Disease occurs when the brain cells that produce the neurotransmitter dopamine deteriorate.  The result may be shaking and difficulty with walking, movment, and coordination.  There is no cure.

         It’s sad but true that we learn more in biology when things go wrong than when things go right.  If a process is going along normally, we can’t see the parts of that process.  But if one or a few parts of the malfunction, suddenly the gaps highlight the missing steps, and we understand the normal process better.

         This has happened with the discovery of genes associated with Parkinson’s Disease.  Even though only a small percentage of cases of Parkinson’s Disease are caused or exacerbated by gene malfunctions, those genes are enlightening Parkinson’s researchers.

         Interestingly, a lot of the genes in question have to do with oxidation and/or waste clean-up in dopamine producing brain cells.  Ultimately this information could lead to new treatments for the disease.  

         If too much of a gene product is gumming up neurons, it could be that stopping or slowing that gene product could prevent the damage.  And it could be that even if the gene is normal in some Parkinson’s sufferers, an environmental factor is causing the same problem.  In that case, the cure might be similar.

         Alternatively, too little of a different gene product might interfere with normal cell clean-up.  The resulting waste accumulation could also gum things up.  Again, environmental factors could mimic this problem.  In either case, some way of supplying the missing molecule(s) might help.

         Food for thought.  I’ll say more about this in my next post.



With Asthma, Which Came First, Genes or Bacteria?

In my last three posts, I’ve been writing about the puzzling and intriguing association between the microbes in our bodies and asthma.  Research seems to show that the lungs and guts of children with asthma house different and less varied communities of bacteria, fungi, and viruses than non-asthmatic children. 

         Research also seems to show that very early exposure to a great variety of such microbes protects against asthma.  For instance, babies raised in rural areas or born vaginally, are far less likely to have asthma than babies born by caesarian section or raised in “clean,” disinfected urban environments.

         However, these connections are merely associations of one condition with another.  We don’t know if there is a cause and effect relationship.  Perhaps the children with asthma are genetically likely to have the disease, and the same genetic make-up also predisposes them to host specific microbial communities in their bodies.  Perhaps on the other hand, the children without asthma have different genes, that protect them from the disease and, at the same time, allow them to host different and more varied microbial communities.

         This is a special version of the quirky “nature or nurture” problem.  Nature or nurture is a human idea that probably has nothing to do with biological reality.  Many such questions turn out to have complex answers or no true answers at all. Unquestionably, the association of health or asthma with various internal communities of bacteria is complicated.  It is a research adventure full of wonder, worth following for some time to come.



Spelunking for a Degree, Part 4: Blind Cave Beetles

Many creatures that live in caves are blind.  Yet their ancestors were sighted.  This is a great example of evolution.

         I did my master’s research on the cave beetle, Ptomaphagus hirtus.  This beetle’s ancestors scavenged for food underneath the leaf litter on forest floors.  Since it’s dark under the leaf litter, eyes were of little use even to these immediate ancestors.  But much earlier ancestors had eyes and used them.

         Though the circumstances differed for the ancestors of other cave animals, like fish or crayfish, the natural selection process was similar.  In the cave, except at the cave mouth, there is absolutely no light.  So eyes are of no use at all.  It takes energy to build eyes, and for living organisms, energy is like money.  The less energy an organism has to expend, the better off that organism is in terms of evolution. 

         Here’s why:  Let’s take my Ptomaphagus beetle.  Like all living things, the Ptomaphagus beetle has to expend energy to mate and lay eggs.  The less energy the beetle expends building and maintaining useless eyes, the more energy it has for building and laying high quality eggs, which lead to successful new beetles.

         “Survival of the fittest” means the most fit beetles will pass on the copies of their genes to more or larger new generations of offspring.  So in a cave, the most fit beetles will be those that lose genes necessary for building and maintaining eyes, for this loss will save energy that otherwise would be wasted.  The very fit blind beetles will pass on all their genes to their offspring, including the mutated eye genes that no longer code for eyes.  Eventually, all the surviving Ptomaphagus beetles will be blind.

          Of course all these blind creatures still must escape predators and must find food, so some of the energy they save in not having vision, must be spent on other senses.  I’ll have more to say about this in my next post.  Stay tuned.



Cells: An Evolutionary Tale

         Since the 1960’s, we have discovered a lot about the evolution of cells.

         Fossil evidence indicated that bacteria had not only been the first living creatures, but they had had the earth to themselves for two billion years. Bacteria are single-celled organisms. Each one carries its genes, made of DNA, in a ring-shaped chromosome folded up in a special region of the cell. Smaller rings of genes, called plasmids, sometimes accompany this chromosome.

         Over two billion years, plenty of mutations took place in bacterial genes, resulting in vast numbers of different bacterial species. Also, being single-celled, bacteria were, and are, capable of picking up chromosome fragments from one another, introducing even more new species.

         About a billion and a half years ago, a new type of organism appeared in the fossil record. Like bacteria, they consisted of single cells. But unlike bacteria, these cells carried their chromosomes enclosed within a special membrane. These membrane-enclosed chromosomes formed a “nucleus” in the new cell type. To distinguish bacteria from the new cells, biologists call bacteria “prokaryotic,” meaning “before the nucleus;” and they called nucleated cells “eukaryotic,” meaning “true nucleus.” Besides the nucleus, the new eukaryotic cells contained a number of infinitesimal organs, called “organelles.” Some of these organelles were photosynthetic and made sugar from light energy. Some did the opposite, extracting energy from sugar to run cell processes.

         Over the next billion and a half years, mutations and gene trading resulted in vast numbers of new eukaryotic species. In some cases, eukaryotic cells joined into multicellular species, such as plants, animals and fungi.

         As François Jacob famously wrote, evolution acts like a tinkerer. Old devices and mechanisms get put to new uses. So it was unlikely that eukaryotic cells had sprung up on their own. It was much more likely that they had somehow evolved out of prokaryotic cells.

         In 1967, Lynn Margulis at Boston University suggested that the first eukaryotic cell could actually have been a group of prokaryotic cells that began living together. In fact, she found that the photosynthetic organelles, called “chloroplasts,” are quite similar to certain photosynthetic bacteria. She also found that the energy-harvesting organelles, called “mitochondria,” are quite similar to certain oxygen-using bacteria. And it turned out that chloroplasts and mitochondria have their own genes, exactly as we might expect, if they were actually bacteria that just happened to be living inside another cell. Margulis’ idea is called the “endosymbiont hypothesis” or the “endosymbiont theory.” It is the beginning of some interesting stories about cell evolution. Stay tuned!

A Little Truth about Genes

I am amazed at the inventiveness of early researchers in pursuit of the secrets of heredity.  With no idea of the true chemistry of genes, investigators designed experiments to reveal genetic facts.

          Geneticists of the 1930’s and ‘40’s believed, incorrectly, that genes must be made of protein.  Yet during this time, George Beadle made his “one gene—one enzyme” discovery.  The discovery came about because Beadle wondered what genes actually do in order to cause traits. 

          First Beadle investigated fruit fly eye colors.  Normal eye color in these flies is a deep-red mixture of red and brown pigments.  Two bright-red mutant colors are vermilion and cinnabar; these contain no brown.  From mutant larvae, Beadle transplanted vermilion and cinnabar eye discs into normal larvae.  The eyes developed normal color in the adult flies.  Cross-mutant transplantation showed Beadle that the brown pigment resulted from a series of chemical reactions: a starting substance got changed to vermilion, which got changed to cinnabar, which got changed to brown.  Each mutant lacked one of these reactions, but it was time-consuming to figure out which one. 

          To speed up his investigation, Beadle switched from fruit flies and eye colors, to red bread mold  Beadle X-rayed the bread mold to cause mutations, then tested spores from the mold to see if they could grow on a minimal food containing only sugars and salts, and the nutrients it manufactured.

          If a mold couldn’t develop on the minimal food, this meant it was missing a nutrient because of a mutation.  Beadle tested to see if the mutation was in a single gene.  If so, Beadle then added a supplement, such as a vitamin or an amino acid.  If that didn’t make the mold grow, he tried a different supplement, until he found the missing nutrient.

          During growth, each mutant mold accumulated a chemical.  This chemical came from the reaction step where the mutant got stuck.  The mutants could be arranged in order, according to where they got stuck, and this order showed the reaction steps in the manufacture of the supplement nutrient.

          Beadle knew that each chemical reaction is controlled by an enzyme.  So each mutant mold must be missing the enzyme that could change its accumulated chemical to the next one in the series.  Since each mutant was missing a single gene, each of those genes must give rise to a single enzyme.  “One gene—one enzyme!”