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Evo Devo and Strange Gods by Gaurang Bhatt, MD

Some cultures including the Hindus of India have a litany of gods and demons with multiple heads and more than two limbs. The idea one presumes, is to show greater brain power, strength and dexterity in the superhuman divine. This thinking is primitive and born out of ignorance in general, but especially of Evo Devo, the new science of evolutionary development. The concept of chimeric gods, as in ancient Egypt ' Horus, Sobet, Isis etc. and Ganesh, Hanuman, Narsinha in India are a faulty imagination on the basis of the same ignorance. Evo Devo, the standard abbreviation for evolutionary development sounds like pidgin Sanskrit and ironically can be loosely translated as 'Only Gods'. 

Three interesting experiments are illuminating. Hans Speman used a fine hair from his child to vertically separate the cells of a newt embryo. Both separated cell masses developed into two identical newt tadpoles. He then used the ligature horizontally to cut the embryo cells into a dorsal and ventral mass. The dorsal half made a normal embryo and the ventral half made a blob of disorganized belly tissue. He then repeated the experiment and this time grafted the dorsal (upper half) lip on to the belly region of another embryo. The receiver embryo then developed two heads, one from its own dorsal half and another from the belly half but using its own cells and not the grafted foreign ones. Spemann concluded that the dorsal region was the organizer. The receiving embryo developed into a newt tadpole with two heads.

Spemann received the Nobel Prize in 1935.

John Sanders, another pioneering scientist found a limb organizer element (localized cell group) in the posterior part of a growing limb bud of a chicken embryo. He transplanted the posterior bud on to the anterior part and managed to grow an extra wing with three digits (chickens have three to our five, one and five are missing in the chicken). The order of the digit growth was digit four nearest the dorsal implant and then three and two further away. Thus the transplanted chicken limb bud had five digits in the order 4,3,2,3,4 starting from the implantation and a double or bifurcated wing. Fred Nijhout in 1980 killed off the cells at the center of an eyespot in the wing of a developing butterfly and noticed that the eyespot on that wing failed to form while the homologous area on the opposite wing had a normal eyespot.

Evo Devo is a new cutting edge branch of science that confirms our origin from simpler organisms by evolution. In the era of ignorance, many in Europe believed that the male sperm was a little homunculus with pre-formed minute body parts and needed a female womb only to nest and grow. This imagined nano-technology of the sperm meant smaller sperms within sperms like regressive Russian dolls. The West with science, observation and even vivisection, learnt the truth that the sperm unites with the ovum to form a zygote which develops as a fetus in the mother's womb and is born as a baby. Watson and Crick discovered that the basis for this process is the DNA of the genome. The modern synthesis of the theory of evolution promulgated that each species has its own complement of genes that leads to differential development giving different forms from mice to humans and amoeba to plants.

The currently proven wrong belief was that bacteria like E. Coli have about 4000 genes and human beings have 100,000 genes explaining their complicated structure. The Human Genome Project revealed a surprise that there is no significant difference in the gene number of mice and men and even the lowly worm and fruit fly have half as many genes as humans. Another surprising finding was that chimpanzees share nearly 98% of the human genome. The question then arises why are we so different from chimpanzees and why our much advanced brains require only twice as many genes as the limited repertoire worm or fly. The answer has a sort of parallel in cooking. One can take carrots and put them in a juicer and get carrot juice, an aperitif, marinate them in vinegar to get an appetizer, saut' or cook them to get an entree or dice and bake them with sugar and milk to get a dessert.

The Nobel Prize winning work of Jacob, Monod and Lwoff on induction of the enzyme beta galactosidase which allows the bacterium to metabolize lactose or milk sugar blazed a new path of understanding. The bacterium normally prefers glucose as its diet, but in the absence of glucose and in the presence of lactose, within three minutes it starts churning out the required enzyme. It has a DNA gene capable of synthesizing a messenger RNA that is used as a template by its ribosomes to make the enzyme protein. This way it avoids wasting energy and effort in making unnecessary proteins from its large genetic complement. The beta galactosidase gene is repressed (inhibited) by another protein of the family of transcription factors which acts like a medieval chastity belt blocking access to the gene. When the bacterium's milieu is full of lactose molecules, they diffuse into its chromosome and attach to the repressor, making it fall off the repressed gene and allow the gene to be transcribed and the enzyme beta galactosidase to be made. There are hundreds of transcription factors that are products of these toolkit genes and they either repress or activate other genes and the algebraic sums of their action modulates the degree of activation or inactivation of other genes. This gives rise to a huge number of combinatorial genes activity which can produce different anatomy and body forms from the same number of similar genes.

There is a gene called PAX-6 which is present in fruit flies, mice and humans (named eyeless, small eye and aniridia respectively) whose malfunction leads to a defective eye and when turned on in an area of a developing body of the fly, mouse or human, it makes an eye even if the location of its turning on is in the wing of the fly, back of the mouse or the forehead of a human. Initially it was believed that eyes have been invented by evolution nearly forty times separately. Now it is proven that in each of this instances from worms and insects to vertebrates, it is this single gene that supervises the formation of an eye like a construction manager. The eyes formed in each animal are different just like the houses built by construction workers using different materials and blueprints lead to different room layouts, wiring and fixtures. There are many toolkit genes like Tinman (from lacking a heart in The Wizard of Oz) which forms the heart, Distal-less that forms the limbs, Bithorax which forms wings, cell type regulators, Hedgehog and other signaling proteins, cellular receptors, hormones, coloration proteins and the most important Homeobox genes that are serially arranged in clusters on chromosomes in order from head, neck, thorax, abdomen and caudal region planners.

Thus a homeobox gene called Antennopedia when mutated causes an extra limb to develop on the head of the fly instead of an antenna. A mutated Bithorax gives rise to an extra pair of wings. Abnormal activation of Distal-less leads to extra fingers and toes in humans and extra eyespots on the wings of a butterfly and a peacock's feathers. Next time you see a person with three eyes, four hands or a pair of wings do not think it is a god, recognize it as a specific genetic mutant. A cyclops (from Homer's Odyssey) has a single eye on its forehead. At one time in the past in Utah, 5 to 7% of newborn sheep were afflicted with cyclopia. It was shown to be due to ingestion of a plant called Veratrum Californicum by the pregnant mother sheep around the fourteenth day of pregnancy. The plant contains a toxin called Cyclopamine that inhibits the transcription factor made by a gene called Sonic Hedgehog (from the video game). Sonic Hedgehog is needed for the bifurcation of the developing brain and its absence leads to Holoprosencephaly, meaning a single forebrain and a cyclopic eye. While humans don't eat the plant, holoprosencephaly is seen in the fetal alcohol syndrome where the pregnant mother abuses alcohol. Sonic Hedgehog activity increase leads to basal cell carcinoma, a common skin cancer of Caucasians and thus the plant toxin is being studied for use in this cancer. 

The genes that make structural proteins and enzymes are like those that make a musical instrument. The transcription factors of toolkit genes are like the musician. Using a violin, one can play Western or Indian classical music, rock, pop music, folk music, any ethnic or national music or just cacophony. It all depends on which strings one uses in which order and for how much time. Making bacteria, fungi, plants or animal bodies is a little bit like that. The strings (genes) are more or less the same, it is how you turn them on that makes the difference. Interested readers may wish to read Monod's book 'Chance and Necessity' and Sean B. Carroll's book 'Endless Forms Most Beautiful' from which the above material is excerpted. The pioneering work on Homeobox genes and development was done by Ed Lewis, Christiane Nusslein-Volhard and Eric Wieschaus, for which they received the Nobel Prize in Medicine for 1995. 


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