The Human Genome Reading the Book of Life

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 all.

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 that all characteristics of the person are “hard-wired” by the genome; and reductionism, the view that with complete knowledge of the human genome sequence, it is only a matter of time before our understanding of gene functions and interactions will provide a complete causal description of human variability. The real challenge of human biology, beyond the task of finding out how genes orchestrate the construction and maintenance of the miraculous mechanism of our bodies, will lie ahead as we seek to explain how our minds have come to organize thoughts sufficiently well to investigate our own existence.”

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.