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, sauté 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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