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!”

"M" Is for the Million Things She Gave Us

In a follicle in the body of a maternal fruit fly or mouse or human being lies an egg cell.

This egg cell is immense compared to the sperm that may eventually fertilize it. A sperm must race vast distances to arrive at the egg in time to compete with millions of other sperm for the fertilization prize, the chance to pass its genes to future generations. So a sperm carries only necessities: a nucleus with the genes packed into chromosomes, high energy molecules and energy-releasing structures to power the long race, a flagellum to swim with, enzymes to dissolve the egg’s protective covering and to signal that this sperm is now fertilizing the egg, and no other sperm may enter.

Once fertilized, the egg cell will divide repeatedly to produce a hollow ball of many identical cells, which will then layer themselves to start developing into an embryo. These early cell divisions happen so fast, the new cells have no time to grow before they divide again. Therefore, except for their chromosomes, which duplicate in full sets before each division, the new cells’ substance and internal structures are all portions of the original egg. So a mother animal must produce an egg large enough to provide all this material.

Next, how do the hundreds of identical new cells wind up becoming different parts of an embryo? How do they turn into head, middle, tail, top, bottom, sides, limbs? We don’t know for sure, but certain clues suggest that the maternal reproductive system conveys this body architecture. Before the egg cell leaves the follicle, molecules from the mother’s body diffuse into it. These molecules are concentrated at one side of the egg, so when the fertilized egg repeatedly divides, some of the new cells will contain a lot of the maternal molecules, and some will contain few or none. So already, the many new cells are not identical. Inside the new cells which contain them, the maternal molecules may produce proteins, and the proteins may signal the new cells to specialize in being the head-end of the embryo. Once these head-end cells specialize, they manufacture their own signals to send to other new cells farther downstream in the incipient embryo, telling them to become the embryo’s mid-section. Then the mid-section cells signal the tail-end cells. Once all these groups of cells start to specialize, they can signal within the group for finer and finer anatomical details.

So like it or not, we owe a lot to Mom.

Lots and Lots of Evolution

    In his Life of the Cosmos, Lee Smolin asks, Why is our universe hospitable to life, and why is it full of stars? Smolin proposes that the universe we inhabit is a product of natural selection: Universes have come and gone, but the most successful ones at reproducing, that is, giving rise to new universes, are the ones that are thick with stars.

    A universe full of stars will also be a universe full of carbon, the very element necessary for life as we know it. Each carbon atom forms four covalent bonds, and carbon atoms bond with other carbon atoms to form long chains, with and without branches. Lots of different atoms and ions can bond all along such carbon chains. Then the chains twist and circle into a vast variety of shapes. And molecules with charge and shape are the working machinery of living cells.

    The first stars in our universe consisted of hydrogen and helium, but as those stars burned out, they produced heavier and heavier elements. Eventually, dying stars exploded into stardust and delivered all 92 natural elements into space. Gravity pulled the stardust together, making it coalesce into new stars, sometimes with planets. One such star is our sun, and one such planet is our earth.

    At first the earth was just a huge, probably hot, ball of chemicals, mostly compounds of the 92 elements. Then the earth cooled, and another kind of evolution began. Water condensed into oceans, and some partly-soluble/partly-insoluble molecules turned their insoluble parts away from the water to form infinitesimal, floating spherical membranes.

    Trapped inside the spheres were various compounds. Many spheres burst like bubbles. But the most successful spheres didn’t burst. Instead, some of their inner compounds produced more soluble/insoluble molecules. These enlarged the membrane until a sphere split into two spheres. To do this, the material inside would need energy, perhaps from the breakdown of other enclosed compounds. Over time, some successful spheres developed ways of taking in more compounds from the ocean to break down for energy or to use in manufacturing more membrane. The longer such spheres were around, the more new, useful compounds they were able to take in or manufacture, and the more useful internal structures they were able to develop. Until eventually some of the spheres actually became very primitive cells, somewhere between life and non-life. This set the stage for yet another evolution: that of living organisms.

What Is Autism Trying to Teach Us?

The rising number of children with autism could be a warning.  Genetically, these children may be especially sensitive to some of the tens of thousands of pollutants in our environment.  

        According to Discover magazine, autism researchers have begun paying attention to the digestive and immune disturbances that accompany the personality aberrations of autism.  Autism is probably connected to genetics.  That’s “genetics,” not “a gene.”  And autism is probably connected to environment.  Like most genetic phenomena, it’s a combination of nature and nurture.

        Genes often work in teams, like this:  All your cells need a certain anti-oxidant molecule.  In each cell, gene 1 in the team manufactures the first part of the anti-oxidant molecule.  Then gene 2 in the team takes the first part of the anti-oxidant and adds a second part.  Then gene 3 adds a third part, and so on until a final gene completes the job.  When the anti-oxidant molecule—let’s call it glutathione—is finished, it can start detoxifying poisonous oxygen radicals that result from daily cell work.

        Now let’s suppose that one of the genes in the glutathione team is handicapped.  Glutathione production slows down. Or the glutathione is defective.  Either way, crowds of oxygen radicals accumulate and interfere with cell functions.  Lots of different kinds of cells suffer when this happens: digestive cells, immune cells, and brain cells, just to name a few.

        One form of suffering brought on by this excess of oxygen radicals has to do with the way cells repair damage from allergens or pollutants.    In addition to the gene team that makes glutathione, each cell has teams of repair genes.  A handicapped gene in a repair team may become even more handicapped when it is stressed by the poisonous accumulation of oxygen radicals.  So repair slows down.  When your cells have unrepaired damage, they send out calls for help, and the first thing your body does is mount a defense that includes inflammation.  If the damage remains unrepaired, the inflammation may become chronic: you get chronic digestive problems, chronic allergic problems, and chronic inflammation of the brain.

        So here and there a handicapped glutathione gene plus a handicapped repair gene might lead to what we call autism.  And the rising number of kids with autism might be an indication of what can happen to human beings in a polluted environment.