How is the genetic code constructed

sickle_s.gif (30476 bytes) People’s Democracy

(Weekly Organ of the Communist Party of India (Marxist)

Vol. XXV

No. 08

February 25, 2001


The Human Genome

Reading the Book of Life

Prabir Purkayastha

THERE are some defining moments in the
history of science. Cracking the atom, the first steps on the moon are such defining
moments. Reading the book of life, the human genome is another such moment. It was
unthinkable that the genetic code consisting of 3 billion letters would be read within ten
years of starting of the human genome project. Last July, it was done by two groups of
scientists – one of which is the publicly funded Human Genome Project spanning 20
laboratories in six countries and the other, a private company Celera Genomics, headed by
the Craig Venter. Both these groups finished a preliminary genome sequence in July last
year and published separately their results last week on the birth anniversary of Charles
Darwin, one in Nature (15 February) and the other in Science (16 February).
The two accounts are remarkably similar confirming that the rough draft of the genomic
sequence is now ready even if the final corrected version takes a little more time.


Nature always springs surprises. The
human genome is no different. The scientists expected about 100,000-140,000 genes.
Instead, the human genome consists of only about 30,000, give or take a couple of
thousand. Compare this to the lowly fruit fly with 13,600 genes and the rice genome with
26,000 genes. Worse, human beings seem to have only 300 genes different from that of the
lowly mouse with whom we shared a common ancestor about 100 million years ago. Venter, in
his Press Conference announcing the sequencing of the Genome said, “The small number
of genes—30,000 instead of 140,000—supports the notion that we are not hard
wired. We now know that the notion that one gene leads to one protein and perhaps one
disease is false.”

Further, Venter continued, “We
now know that the environment acting on these biological steps may be key in making us
what we are. Likewise, the remarkably small number of genetic variations that occur in
genes again suggest a significant role for environmental influences in developing each of
our uniqueness.”
In the Nature versus Nurture debate, in which IQ to criminal
behaviour have all been attributed by some to genes and heredity, the genome’s
unravelling gives a clear refutation of the Nature position.

On the question of race, the
genome’s answer is again categorical. A very small number of genes are involved in
skin pigmentation. Paablo Svante, writing in this genome issue of Science, says,
“From a genetic perspective, all humans are therefore Africans, either residing in
Africa or in recent exile.” Further, he continues, ” it is clear that what is
called “race,” although culturally important, reflects just a few continuous
traits determined by a tiny fraction of our genes. This tiny fraction gives no indication
of variations at other parts of our genome. Thus, from the perspective of nuclear genes,
it is often the case that two persons from the same part of the world who look
superficially alike are less related to each other than they are to persons from other
parts of the world who may look very different.” In his Press Note Venter says,
We are confident that our sequence will help to demonstrate that the human
genome will not aid those who want to perpetuate racial prejudice.”


How is the genetic code constructed? Any
computer code – any statement or a number within the computer – is an
arrangement of zero’s and ones. This is the binary code. The genetic code is the set
of biological instructions needed to make a human being and is also similarly constructed.
All genetic code is spelled out with just four chemical letters, or bases: adenine (A),
thymine (T), cytosine (C) and guanine (G). These bases pair up, A with T and C with G. A
DNA double helix, if is untangled would look like a stepladder with each rung composed of
such pairs. The “up-rights” of this ladder are composed of a sugar molecule
called de-oxyribose. Running up and down the ladder are the long sequences of bases, which
are the code for life. Genes are special sequences of hundreds or thousands of base pairs
that provide the “recipe” for all the proteins that the body needs to produce.
Each cell in the human body contains two metres (six feet) of DNA. A DNA genetic code of
the cell nucleus is thus a series of such pairs as given below:

How many of these letters do we carry?
Human beings have 3 billion such letters in their genetic code. Human beings are
highly homogenous in their genetic make up: a group of 55 apes in Africa show more genetic
variations than the entire human population of 5 billion!

The unravelled genome sequence shows
that as little as 1.4 per cent of the total genome is made of genes, the rest is
“junk”. These genes and all the junk DNA are wrapped up into bundles called
chromosomes. Every human has 23 pairs of chromosomes, one set from each parent. The 46
chromosomes are held in the nucleus found in most cells in the human body. Nearly every
cell in the body contains the full DNA code for producing a human. Each of the cells
becomes specialised by obeying just some of the instructions in the DNA. Blood, muscle,
bone, organs and so on are the result. The body is built from 100 trillion of these cells.

If human beings carry same genes, how
are they different? The answer lies in it that they do not carry identical spellings in
each gene: each human being has some variations. Even though any two individuals are more
than 99.9 per cent identical in sequence, all the difference between two individuals are
due to this mere 0.1 per cent difference in their genetic code.


If the complexity of human beings is not
hardwired, how do we explain the complex human behaviour that distinguishes us from the
fruit fly? The answers are currently hazy. David Baltimore of California Institute of
Technology, writing in Nature says, “it is clear that we do not gain our undoubted
complexity over worms and plants by using many more genes. Understanding what does give us
our complexity — our enormous behavioural repertoire, ability to produce conscious
action, remarkable physical coordination (shared with other vertebrates), precisely tuned
alterations in response to external variations of the environment, learning, memory. . .
need I go on? — remains a challenge for the future.” Some of the answers being
discussed are that the junk DNA may not be junk after all or complexity could be
combinatorial. It is possible to create astronomical variations by 30,000 genes if we take
various combinations into account. Venter argues that we should see genes not as a part
list but as a network. It is the interaction within and among the network elements that
create the complexity that we see.

In the lead article in Nature, “The
Initial Sequencing and Analysis of the Human Genome”, International Human Genome
Sequencing Consortium discusses the possible causes of complexity of mammalian and human
behaviour. The paper notes that though the number of genes is not significantly more, the
vertebrate genes can spell out more proteins than their fruit fly counterparts.
Vertebrates seem to also have shuffled their proteins to produce new combinations even
though the basic building blocks remain largely the same. The paper of the Consortium
says, “.. the relatively greater complexity of the human proteome (complete set of
proteins coded by the genome) is a consequence not simply of its larger size, but also of
large-scale protein innovation.”

While protein innovation may
differentiate between the vertebrates and others, it is unlikely that the differences
between chimpanzee and human genome are going to be significantly different at the protein
level. Thus, protein complexities in no way are going to explain the enormous change that
has come about in the human species in the last 150,000 years. The change of only a few
genes has resulted in the growth of the brain, rise of speech and tool making abilities in
human beings. It is sobering and enormously humbling for human beings to know that they
have arisen from a few genetic accidents. The complexities of human civilisation thus lie
in enabling cultural evolution to take place rather than the earlier expectation of a long
history of physical evolution. Human uniqueness lies not in our genes but in our culture


By reading the genetic code, we now know
where all the action is in the DNA is. Why there is so-much junk DNA is still not clear.
Some of its importance may lie in its past, some to its ability to transfer genetic
material from one part to another. Venter has speculated that the answer to complexity of
higher mammals may lie in this junk “DNA”, which therefore may not be junk after

The genome has another surprise for us
apart from its small size. Bacterial genetic material has been found in the genes. These
do not appear to be old DNA from the days of our common ancestry. Baltimore states in Nature,
“A few of our genes seem to have come directly from bacteria, rather than by
evolution from bacteria — apparently bacterial genomes can be direct donors of genes
to vertebrates.”


The ideological world of free market
loves genetic determinism. This, according to these ideologues, explains the status quo
completely. The poor are poor as they have bad genes; whether it is “lower
castes” or the “lower races” – the black and brown ones – all
their problems are writ in their genes. Venter’s warning here is particularly
relevant, “There are two fallacies to be avoided: determinism, the idea thatall
characteristics of the person are “hard-wired” by the genome;and
reductionism, the view that with complete knowledge of thehuman genome
sequence, it is only a matter of time before ourunderstanding of gene
functions and interactions will providea complete causal description of human
variability. The real challengeof human biology, beyond the task of finding
out how genes orchestratethe construction and maintenance of the miraculous
mechanism ofour bodies, will lie ahead as we seek to explain how our mindshave come to organize thoughts sufficiently well to investigateour own

We must end here on a note of caution.
The cracking of the atom produced the ability to destroy all life on this planet but very
little of benefit on the flip side. The giant steps for mankind – man’s steps on
moon – are recognised now as mere vainglory and of no benefit to either science or
humanity. The cracking of the genetic code, another such defining moment, has enormous
potential for human good as well as pure evil.


Science by itself does not produce
advances for humanity, more so today when we have acquired abilities far beyond our
wisdom. This is the challenge that the human race faces today. Whether we will get drugs
at astronomical prices, with all genetic knowledge patented by the drug companies,
designer babies for the rich and a large part of the population without health care that
is uninsurable due to genetic “defects”, depend on what kind of society we want
to build. The two approaches to unravelling the genome – public domain
science, as was the international consortium or private domain science as was the Celera
effort — are issues that have vital bearings on our future. We will take up some of these
issues in the next issue.

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