What Is Life (Canto Classics) Page 4
These anticipations have been fully confirmed. In the cases to which tests have been thoroughly applied (mainly, but not only, Drosophila) the tested properties actually divide into as many separate groups, with no linkage from group to group, as there are different chromosomes (four in Drosophila). Within every group a linear map of properties can be drawn up which accounts quantitatively for the degree of linkage between any two out of that group, so that there is little doubt that they actually are located, and located along a line, as the rod-like shape of the chromosome suggests.
Of course, the scheme of the hereditary mechanism, as drawn up here, is still rather empty and colourless, even slightly naïve. For we have not said what exactly we understand by a property. It seems neither adequate nor possible to dissect into discrete ‘properties’ the pattern of an organism which is essentially a unity, a ‘whole’. Now, what we actually state in any particular case is, that a pair of ancestors were different in a certain well-defined respect (say, one had blue eyes, the other brown), and that the offspring follows in this respect either one or the other. What we locate in the chromosome is the seat of this difference. (We call it, in technical language, a ‘locus’, or, if we think of the hypothetical material structure underlying it, a ‘gene’.) Difference of property, to my view, is really the fundamental concept rather than property itself, notwithstanding the apparent linguistic and logical contradiction of this statement. The differences of properties actually are discrete, as will emerge in the next chapter when we have to speak of mutations and the dry scheme hitherto presented will, as I hope, acquire more life and colour.
MAXIMUM SIZE OF A GENE
We have just introduced the term gene for the hypothetical material carrier of a definite hereditary feature. We must now stress two points which will be highly relevant to our investigation. The first is the size – or, better, the maximum size – of such a carrier; in other words, to how small a volume can we trace the location? The second point will be the permanence of a gene, to be inferred from the durability of the hereditary pattern.
As regards the size, there are two entirely independent estimates, one resting on genetic evidence (breeding experiments), the other on cytological evidence (direct microscopic inspection). The first is, in principle, simple enough. After having, in the way described above, located in the chromosome a considerable number of different (large-scale) features (say of the Drosophila fly) within a particular one of its chromosomes, to get the required estimate we need only divide the measured length of that chromosome by the number of features and multiply by the cross-section. For, of course, we count as different only such features as are occasionally separated by crossing-over, so that they cannot be due to the same (microscopic or molecular) structure. On the other hand, it is clear that our estimate can only give a maximum size, because the number of features isolated by genetic analysis is continually increasing as work goes on.
The other estimate, though based on microscopic inspection, is really far less direct. Certain cells of Drosophila (namely, those of its salivary glands) are, for some reason, enormously enlarged, and so are their chromosomes. In them you distinguish a crowded pattern of transverse dark bands across the fibre. C. D. Darlington has remarked that the number of these bands (2,000 in the case he uses) is, though considerably larger, yet roughly of the same order of magnitude as the number of genes located in that chromosome by breeding experiments. He inclines to regard these bands as indicating the actual genes (or separations of genes). Dividing the length of the chromosome, measured in a normal-sized cell by their number (2,000), he finds the volume of a gene equal to a cube of edge 300 Å. Considering the roughness of the estimates, we may regard this to be also the size obtained by the first method.
SMALL NUMBERS
A full discussion of the bearing of statistical physics on all the facts I am recalling- or perhaps, I ought to say, of the bearing of these facts on the use of statistical physics in the living cell – will follow later. But let me draw attention at this point to the fact that 300 Å is only about 100 or 150 atomic distances in a liquid or in a solid, so that a gene contains certainly not more than about a million or a few million atoms. That number is much too small (from the √n point of view) to entail an orderly and lawful behaviour according to statistical physics – and that means according to physics. It is too small, even if all these atoms played the same role, as they do in a gas or in a drop of liquid. And the gene is most certainly not just a homogeneous drop of liquid. It is probably a large protein molecule, in which every atom, every radical, every heterocyclic ring plays an individual role, more or less different from that played by any of the other similar atoms, radicals, or rings. This, at any rate, is the opinion of leading geneticists such as Haldane and Darlington, and we shall soon have to refer to genetic experiments which come very near to proving it.
PERMANENCE
Let us now turn to the second highly relevant question: What degree of permanence do we encounter in hereditary properties and what must we therefore attribute to the material structures which carry them?
The answer to this can really be given without any special investigation. The mere fact that we speak of hereditary properties indicates that we recognize the permanence to be almost absolute. For we must not forget that what is passed on by the parent to the child is not just this or that peculiarity, a hooked nose, short fingers, a tendency to rheumatism, haemophilia, dichromasy, etc. Such features we may conveniently select for studying the laws of heredity. But actually it is the whole (four-dimensional) pattern of the ‘phenotype’, the visible and manifest nature of the individual, which is reproduced without appreciable change for generations, permanent within centuries – though not within tens of thousands of years – and borne at each transmission by the material structure of the nuclei of the two cells which unite to form the fertilized egg cell. That is a marvel – than which only one is greater; one that, if intimately connected with it, yet lies on a different plane. I mean the fact that we, whose total being is entirely based on a marvellous interplay of this very kind, yet possess the power of acquiring considerable knowledge about it. I think it possible that this knowledge may advance to little short of a complete understanding – of the first marvel. The second may well be beyond human understanding.
1 Being is eternal; for laws there are to conserve the treasures of life on which the Universe draws for beauty.
2 The word means ‘the substance which takes on colour’, viz. in a certain dyeing process used in microscopic technique.
3 Ontogenesis is the development of the individual, during its lifetime, as opposed to phylogenesis, the development of species within geological periods.
4 Very roughly, a hundred or a thousand (English) billions.
5 The biologist will forgive me for disregarding in this brief summary the exceptional case of mosaics.
6 At any rate, every woman. To avoid prolixity, I have excluded from this summary the highly interesting sphere of sex determination and sex-linked properties (as, for example, so-called colour blindness).
CHAPTER 3
Mutations
Und was in schwankender Erscheinung schwebt,
Befestiget mit dauernden Gedanken.1
GOETHE
‘JUMP-LIKE’ MUTATIONS – THE WORKING -
GROUND OF NATURAL SELECTION
The general facts which we have just put forward in evidence of the durability claimed for the gene structure, are perhaps too familiar to us to be striking or to be regarded as convincing. Here, for once, the common saying that exceptions prove the rule is actually true. If there were no exceptions to the likeness between children and parents, we should have been deprived not only of all those beautiful experiments which have revealed to us the detailed mechanism of heredity, but also of that grand, million-fold experiment of Nature, which forges the species by natural selection and survival of the fittest.
Let me take this last important subject as the starting-point for pr
esenting the relevant facts – again with an apology and a reminder that I am not a biologist:
We know definitely, today, that Darwin was mistaken in regarding the small, continuous, accidental variations, that are bound to occur even in the most homogeneous population, as the material on which natural selection works. For it has been proved that they are not inherited. The fact is important enough to be illustrated briefly. If you take a crop of pure-strain barley, and measure, ear by ear, the length of its awns and plot the result of your statistics, you will get a bell-shaped curve as shown in Fig. 7, where the number of ears with a definite length of awn is plotted against the length. In other words: a definite medium length prevails, and deviations in either direction occur with certain frequencies. Now pick out a group of ears (as indicated by blackening) with awns noticeably beyond the average, but sufficient in number to be sown in a field by themselves and give a new crop. In making the same statistics for this, Darwin would have expected to find the corresponding curve shifted to the right. In other words, he would have expected to produce by selection an increase of the average length of the awns. That is not the case, if a truly pure-bred strain of barley has been used. The new statistical curve, obtained from the selected crop, is identical with the first one, and the same would be the case if ears with particularly short awns had been selected for seed. Selection has no effect – because the small, continuous variations are not inherited. They are obviously not based on the structure of the hereditary substance, they are accidental. But about forty years ago the Dutchman de Vries discovered that in the offspring even of thoroughly pure-bred stocks, a very small number of individuals, say two or three in tens of thousands, turn up with small but ‘jump-like’ changes, the expression ‘jump-like’ not meaning that the change is so very considerable, but that there is a discontinuity inasmuch as there are no intermediate forms between the unchanged and the few changed. De Vries called that a mutation. The significant fact is the discontinuity. It reminds a physicist of quantum theory – no intermediate energies occurring between two neighbouring energy levels. He would be inclined to call de Vries’s mutation theory, figuratively, the quantum theory of biology. We shall see later that this is much more than figurative. The mutations are actually due to quantum jumps in the gene molecule. But quantum theory was but two years old when de Vries first published his discovery, in 1902. Small wonder that it took another generation to discover the intimate connection!
Fig. 7. Statistics of length of awns in a pure-bred crop. The black group is to be selected for sowing. (The details are not from an actual experiment, but are just set up for illustration.)
THEY BREED TRUE, THAT IS, THEY ARE
PERFECTLY INHERITED
Mutations are inherited as perfectly as the original, unchanged characters were. To give an example, in the first crop of barley considered above a few ears might turn up with awns considerably outside the range of variability shown in Fig. 7, say with no awns at all. They might represent a de Vries mutation and would then breed perfectly true, that is to say, all their descendants would be equally awnless.
Hence a mutation is definitely a change in the hereditary treasure and has to be accounted for by some change in the hereditary substance. Actually most of the important breeding experiments, which have revealed to us the mechanism of heredity, consisted in a careful analysis of the offspring obtained by crossing, according to a preconceived plan, mutated (or, in many cases, multiply mutated) with non-mutated or with differently mutated individuals. On the other hand, by virtue of their breeding true, mutations are a suitable material on which natural selection may work and produce the species as described by Darwin, by eliminating the unfit and letting the fittest survive. In Darwin’s theory, you just have to substitute ‘mutations’ for his ‘slight accidental variations’ (just as quantum theory substitutes ‘quantum jump’ for ‘continuous transfer of energy’). In all other respects little change was necessary in Darwin’s theory, that is, if I am correctly interpreting the view held by the majority of biologists.2
Fig. 8. Heterozygous mutant. The cross marks the mutated gene.
LOCALIZATION. RECESSIVITY AND DOMINANCE
We must now review some other fundamental facts and notions about mutations, again in a slightly dogmatic manner, without showing directly how they spring, one by one, from experimental evidence.
We should expect a definite observed mutation to be caused by a change in a definite region in one of the chromosomes. And so it is. It is important to state that we know definitely that it is a change in one chromosome only, but not in the corresponding locus’ of the homologous chromosome. Fig. 8 indicates this schematically, the cross denoting the mutated locus. The fact that only one chromosome is affected is revealed when the mutated individual (often called ‘mutant’) is crossed with a non-mutated one. For exactly half of the offspring exhibit the mutant character and half the normal one. That is what is to be expected as a consequence of the separation of the two chromosomes on meiosis in the mutant – as shown, very schematically, in Fig. 9. This is a ‘pedigree’, representing every individual (of three consecutive generations) simply by the pair of chromosomes in question. Please realize that if the mutant had both its chromosomes affected, all the children would receive the same (mixed) inheritance, different from that of either parent.
Fig. 9. Inheritance of a mutation. The straight lines across indicate the transfer of a chromosome, the double ones that of the mutated chromosome. The unaccounted-for chromosomes of the third generation come from the mates of the second generation, which are not included in the diagram. They are supposed to be non-relatives, free of the mutation.
But experimenting in this domain is not as simple as would appear from what has just been said. It is complicated by the second important fact, viz. that mutations are very often latent. What does that mean?
In the mutant the two ‘copies of the code-script’ are no longer identical; they present two different ‘readings’ or versions’, at any rate in that one place. Perhaps it is well to point out at once that, while it might be tempting, it would nevertheless be entirely wrong to regard the original version as ‘orthodox’, and the mutant version as ‘heretic’. We have to regard them, in principle, as being of equal right – for the normal characters have also arisen from mutations.
Fig. 10. Homozygous mutant, obtained in one-quarter of the descendants either from self-fertilization of a heterozygous mutant (see Fig. 8) or from crossing two of them.
What actually happens is that the ‘pattern’ of the individual, as a general rule, follows either the one or the other version, which may be the normal or the mutant one. The version which is followed is called dominant, the other recessive; in other words, the mutation is called dominant or recessive, according to whether it is immediately effective in changing the pattern or not.
Recessive mutations are even more frequent than dominant ones and are very important, though at first they do not show up at all. To affect the pattern, they have to be present in both chromosomes (see Fig. 10). Such individuals can be produced when two equal recessive mutants happen to be crossed with each other or when a mutant is crossed with itself; this is possible in hermaphroditic plants and even happens spontaneously. An easy reflection shows that in these cases about one-quarter of the offspring will be of this type and thus visibly exhibit the mutated pattern.
INTRODUCING SOME TECHNICAL LANGUAGE
I think it will make for clarity to explain here a few technical terms. For what I called ‘version of the code-script’ – be it the original one or a mutant one – the term ‘allele’ has been adopted. When the versions are different, as indicated in Fig. 8, the individual is called heterozygous, with respect to that locus. When they are equal, as in the non-mutated individual or in the case of Fig. 10, they are called homozygous. Thus a recessive allele influences the pattern only when homozygous, whereas a dominant allele produces the same pattern, whether homozygous or only heterozygous.
Col
our is very often dominant over lack of colour (or white). Thus, for example, a pea will flower white only when it has the ‘recessive allele responsible for white’ in both chromosomes in question, when it is ‘homozygous for white’; it will then breed true, and all its descendants will be white. But one ‘red allele’ (the other being white; ‘heterozygous’) will make it flower red, and so will two red alleles (‘homozygous’). The difference of the latter two cases will only show up in the offspring, when the heterozygous red will produce some white descendants, and the homozygous red will breed true.
The fact that two individuals may be exactly alike in their outward appearance, yet differ in their inheritance, is so important that an exact differentiation is desirable. The geneticist says they have the same phenotype, but different genotype. The contents of the preceding paragraphs could thus be summarized in the brief, but highly technical statement: