Genome - The Autobiography of a Species
The Prophet of Prophecy
British science journalist Matt Ridley has written an unusual popular-scientific book: In 23 chapters, the autobiography of the human species is told - each of these chapters correspond with one of a human cell's 23 chromosome pairs. From each chromosome Ridley has picked one or a group of genes, which gave him the topics for the individual chapters.
Ridley starts with the origin of life and human genealogy, then ventures into the history of genetics as a branch of science. Many of the following chapters then deal with particular features caused by genes. Even though Ridley keeps repeating the phrase "Genes are not there to cause diseases", sometimes even in capital letters, diseases are also one of the topics of many chapters; he tells us about research on genetic causes of Alzheimer and Huntington's diseases, asthma and cholera, and so on. A chapter is also dedicated to eugenics, another on cure of illnesses by somatic and germ-line therapy - these parts of the book somewhat resemble The Biotech Century. Some details, such as the tests for Tay-Sachs disease initiated by Ashkenazi Jewish communities, appear in both books. The last chapter is a pseudo-philosophical rambling on determinism versus free will - apparently Schrödinger's What is Life? has inspired the author so much that he decided to end the book in the same way.
I am not going to write chronologically about the contents of each and every chapter, but I am trying to extract the most valuable knowledge from Ridley's popular-scientific narrative.
In a short primer, the unprepared layman first gets introduced to the very basics of modern genetics: The human body consists of a huge number of cells with a "black blob" called nucleus, which contains the 23 chromosome pairs that store our inherited genes. Each chromosome is a pair of two very long DNA molecules, which store genetic information encoded with four "letters" (in fact bases), A(denine), C(ytosine), G(uanine) and T(hymine). The usual state of DNA is the double-helix, in which the original pair and its complementary - T for A, C for G and vice-versa - are inertwinded. The complementary bases love to pair, in which way it is possible for DNA to replicate itself. When a part of DNA that has a function (gene) is switched on (expressed), it is first transcribed into RNA, which is then translated into complex proteins, made up of twenty different amino-acids. The proteins control development and partly even behaviour of the organism.
The narrative starts with a ribosomal RNA gene in our largest chromosome, which resembles the RNA that is created by an experiment in a test-tube simulating the possible origin of life. It is assumed that RNA came long before DNA, that DNA - which, after all, only differs from RNA in so far as it has the "letter" T instead of U - was "invented" by RNA as a more secure host of genetic information. Scientists assume the first creature that stored its genetic information in DNA must have been the Last Universal Common Ancestor (Luca) of all creatures alive today.
Chapter 2 proceeds with the history of the human species in particular, by pointing out that our second largest chromosome is the merger of two ape-chromosomes. The information that chimpanzees and human beings share 98% of their genes is widely known. We also share more than nine tenths of our genetic makeup with the other apes. In fact at some stage in the course of evolution a common ancestor of chimps and us must have separated from the other apes. Due to a natural event a small tribe probably was geographically separated from the chimps for a long time and mutated so much that a new species was created which could no longer breed with chimpanzees. We, their descendants, vary less in our genome than chimps do. It is assumed that the development of our brain capacities were fostered by monogamy. Instead of polygamy or totally uncontrolled breeding like in other apes, men and women carefully selected their partners. (I am not fully convinced of this theory, as there is also polygamy among many human tribes, and even in our society the rules of monogamy are often neglected. But of course, for thousands of years, natural selection caused organisms incapable of surviving to die.) It is surprising that we now control this world, as the reptiles we are ancestors of as well as all apes went close to extinction millions of years ago.
After these two chapters on evolution Ridley enters the history of genetics. We learn about Gregor Mendel, whose breeding experiments with beans and other plants showed certain patterns of inheritance. Years before James Watson and Francis Crick discovered the DNA double-helix of which chromosomes were constructed, the hereditary mechanism was already known. Usually, you inherit 22 equal (but not identical) chromosomes from both of your parents. The 23th pair is made up of an X chromosome contributed by your mother and either an X or a Y chromosome from your father. The default sex is female, only if you get the Y chromosome, you will develop male characteristics. So most of your cells carry two gene-sets. An exception is sex cells: They are created by meiosis. They carry only one genetic set, which is a random mix of genes from your father and genes from your mother. This is the reason why your children are genetically different, except if they are identical twins.
Sometimes mistakes are made during the replication of chromosomes, for example some of the bases may be replaced. This is what we call a mutation; it may be harmful or even lethal, but sometimes it is beneficial. Recall that we are close relatives of chimpanzees. Only a few mutations caused the difference.
Luckily getting a potentially harmful mutation does not mean it will immediately destroy you. This is because genes are expressed at different stages; when particular genes are expressed and why exactly they are expressed at this stage, is still a mystery. It is important to keep in mind that you have two sets of chromosomes. Some genes are only expressed if the same version of the gene is in both chromosomes. These genes are called recessive. Dominant genes, by constrast, are expressed even if only a single copy is present.
This explains why there are features that appear in every generation of a family, while some others are skipped in one generation but re-appear in the next. It also explains why incest often causes dangerous diseases: There is more chance that you inherit a recessive mutation from both of your parents.
The task of genes is to produce proteins, which in combination with enzymes and hormones control the body. It is still not fully clear how DNA, transcribed into RNA, exactly translates into amino acids that make up specific proteins. Francis Crick invented an ingenious comma-free code: Assuming each genetic 'instruction' consisted of three subsequent letters and it were not possible to misread a genetic 'program' by starting to read at the wrong letter, there would be exactly twenty possible instructions - one for each amino acid. But this code is not the same as nature uses. Chromosomes not only consist of genes. In fact only about two percent is genetic data; the rest is "junk" DNA that has no function, except perhaps replicating itself.
Throughout the book we get to learn a unusual view of life: that in fact bodies are only designed as temporary containers of genes. Ridley shows many examples of selfish genes that seem to deliberately disturb the working of other genes. For example, some genes on the X chromosome apparently suppress parts of the Y chromosome and thus do damage when they are in male bodies, but are of no disadvantage if they are in females. There seems to be antagonism, or even war between the genes that make their hosts male or female. It has been noticed, for example, that the semen fluid of some male flies is designed to make the females addicted to this particular individual's fluid, so that they will not change their partner. But mutations make females gradually get resistant to this effect. In an experiment, a separate female strain was kept that did not evolve resistance. At the same time males were tested against increasingly resistant females in order to allow them to generate more effective fluid. After 29 generations he brought the two lines together again. The result: Male fluid was so toxic for the females that it could kill them. Such evidence contradicts the classical notion that natural selection is supposed to improve and sustain the species.
But it is also interesting that the sexual origin of a chromosome seems to matter. For example, a girl with Turner's syndrome who inherits only one X chromosome from her mother and none from her father has low social skills, worse than a boy. The situation is a bit better if she inherits just the paternal X chromosome. But: The paternal X chromosome she inherits from her father is - unless a mutation occurred - identical to his maternal X chromosome. So not only the genetic information seems to matter but also from whom you inherit it.
What I found very interesting as well was a study presented in chapter 14, Pre-History. An Italian scientist wanted to find out if there were any correlations between linguistic and genetic roots. So he collected the genes of many people living in all parts of Europe. The result: There are five different contour maps of gene frequencies within Europe. One is from south-east to north-west, resembling the original spread of neolithic farmers. It accounts for 28% of the genetic variation in his sample. The second, accounting for 22%, is a steep hill into the north-west, apparently reflecting the genes of Uralic speakers. Slightly weaker peaks were found in the Ukrainian steppes, the regions where the ancient Greeks settled, and the original Basque country in northern Spain and southern France. There were also local concentrations of unusual genetic mutations in some smaller regions, for example Genoa, where a Ligurian dialect used to be spoken.
"Genes, in other words, support the evidence from linguistics that expansions and migrations of people with novel technological skills have played a great part in human evolution." They also confirm the hypothesis that tribes with superior technologies intruding into already occupied land banned the natives' men and had their own men marry the natives' women. For example, the genes of Finnish people do not vary much from other Scandinavians' genes, except that they share the male Y chromosomes with Uralic people.
I found this book extraordinarily interesting and a valuable introduction to the human genome as well as genes in general. In fact I read it after The Biotech Century, but it would have been better to do it the other way round, to get introduced into theory before dealing with applications and implications.
I think books like this are necessary to open the eyes of a broad public how interesting the science of genetics is and that dangers of some of its applications should be no reason to stop research altogether, as some extremists demand.
Genetics could bring us a large step closer to the answer of a major philosophical question: about the sense of life.
Adok/Hugi - 30 Aug 2000