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Rockefeller University Digital Commons @ RU The Rockefeller Institute Quarterly The Rockefeller University Newsletters Summer 1958 The Rockefeller Institute Quarterly 1958, vol. 2, no. 2 The Rockefeller University Follow this and additional works at: http://digitalcommons.rockefeller.edu/ rockefeller_institute_quarterly Recommended Citation The Rockefeller University, "The Rockefeller Institute Quarterly 1958, vol. 2, no. 2" (1958). The Rockefeller Institute Quarterly. Book 6. http://digitalcommons.rockefeller.edu/rockefeller_institute_quarterly/6 This Book is brought to you for free and open access by the The Rockefeller University Newsletters at Digital Commons @ RU. It has been accepted for inclusion in The Rockefeller Institute Quarterly by an authorized administrator of Digital Commons @ RU. For more information, please contact [email protected]. VOLUME 2 NUMBER 2 SUMMER 1958 BIOCHEMICAL GENETICS AND The life cycle of Neurospora was well understood many years ago, thanks to the studies of Dr. B. 0.Dodge at the New INHERITED METABOLIC DISEASE York Botanical Garden. It is a microorgan- ism that exists in two sexes so that cross- THE IDEA THAT not only gross traits of which cause them are in some cases rather breeding experiments are possible, and the species and individuals are genetically de- well understood. Wilson's disease, which cycle from infancy to maturity is only lo termined but that even detailed biochem- we shall describe later, is one of them. But days. The fungus also multiplies asexually, ical processes are gene-controlled owes on the whole, man is not a very suitable that is by simple division, so that billions much to the work of Dr. Edward L. Tatum, organism for any kind of genetic studies. of individuals with identical hereditary now at The Rockefeller Institute. In this His life cycle is long, his offspring are rela- traits can quickly be grown in the labora- article we will tell something about studies tively few, and experimental cross-breed- tory. Some other virtues of Neurospora, of metabolic disorders in bacteria and ing, so important in genetics, is out of the however, are especially important for bio- fungi, and we will also describe similar question. It is no wonder that geneticists chemical and genetic studies. First, it can work at the Institute with other organisms. have concentrated on other organisms, be grown on a very simple medium (even Dr. Sam Granick, for example, has found among them being mice, the fruit fly, and simpler than bread, where we often find the genetic techniques pioneered by Dr. corn. While these are useful organisms for it), which means that many links in elab- Tatum to provide a key to unravelling a genetic studies, the fungus Neurospora is orate biochemical chains can be studied, part of the biosynthesis of porphyrin, an preferable for biochemical studies for sev- starting from scratch, so to speak, and end- essential component in the synthesis of eral reasons. (continued on next page) those key molecules of plant and animal life, chlorophyll and hemoglobin. And Dr. A. G. Bearn, also at The Rockefeller Insti- tute, has been interested in a hereditary metabolic disorder in man known as Wil- son's disease. It may surprise many readers to be told that our present understanding of the way genes control biochemical processes in or- ganisms as dissimilar as yeast and men rests heavily on studies of the inheritance of nutritional deficiencies in the red bread mold, Neurospora crassa. But the studies of this simple organism, undertaken by Dr. Tatum at Stanford University nearly 20 years ago with Dr. George Beadle-now Professor and Chairman of the Division of Biology at the California Institute of Tech- nology-have vastly increased our knowl- edge of both biochemistry and genetics. A number of inherited metabolic dis- orders in man have been known for a long time, and the specific biochemical defects Spores of Neurospora sitophila, enlarged about 500 times. Photo courtesy Dr. B. 0.Dodge. ing with such complex materials as the large enough for biochemical study. The that only one nutritional item was not syn- vitamins. photograph on page one shows a much- thesized. This is interpreted to mean that To explain more of the other virtues of magnified view of several spore capsules, if a gene is damaged it is not able to pro- Neurospora we must recall some of the each with its eight spores. The organism vide the cell with a certain enzyme neces- mechanics of genetics and sexual repro- shown is Neurospora sitophikz, a close rela- sary to permit a given step in a chain of duction. In man and most higher organ- tive of crassa. biochemical reactions to proceed. Now isms there are two sets of genes present in If we now introduce the idea of muta- since an elaborate molecule such as a vita- all cells, one set of which was obtained tion into the story we shall have all the min is not fabricated in a single step, but from each parent. Each set appears to have genetic ideas necessary to complete our ac- in several successive steps, it is reasonable something to do with nearly all of our in- count. Return to the blue-eyed child of the to suppose that defects in any of several herited characteristics, but in some cases dark-eyed parents. It is clear that both of genes (each responsible for a given en- the gene from one set overshadows the its eye-color genes were "blue." Now sup- zyme and hence for a given step in a bio- effect of the corresponding gene in the pose that two such individuals marry. If synthesis) may give rise to the same nutri- other set. For example, suppose a gene for all goes according to our simplified presen- tional deficiency. It is as if in an assembly dark eyes is contributed to a child by the tation there should not be a dark-eyed gene line in a factory several stages of produc- father and one for blue eyes by the mother. anywhere to be found, and all the children tion could be interfered with, any one of The color of the child's eyes will not be of such a marriage should have blue eyes. which could stop the output of the final arrived at by compromise; they will be In fact, something can go wrong with the product. dark. The blue-eyed gene is present, but genes of one of the parents, and a heritable it does not express itself, i.e., it is said to dark-eye pigment may appear in one or AN AMINO ACID SEQUENCE be recessive. This causes surprises in the more of their children. Something like this Srb and Horowitz at Stanford Univer- families of dark-eyed parents. For if two often happens. It is called a mutation, sity, for example, found three different such dark-eyed individuals bearing reces- meaning a change in a genh. Unfortu- mutant strains of Neurospora, each of sive blue-eyed genes marry, the recessive nately, most of these gene changes could which required a supplement of the amino genes from each parent may both appear be better called damages, for mutations are acid, arginine. However, different stages in the same child. In this case there is no usually deleterious. This is because they in the assembly line for producing arginine "dark gene to cover them up, so to speak, are the result of apparently random changes were disrupted in each strain. One, for and a blue-eyed child is born to dark-eyed in the genes. Mutations are caused by example, could not live without arginine, parents. The double gene-set arrangement, such things as nuclear and cosmic radi- but another could apparently make its own therefore, complicates analysis. Neurospora ation, X-rays, and certain chemicals in our arginine provided citrulline were available obligingly dispenses with it. Its nuclei con- environment. instead. The third strain could get along tain only one set of genes, and whatever is Indeed Beadle and Tatum's experiments with either arginine or citrulline or even contained in the gene collection of an in- with Neurospora depended on the possibil. with ornithine. Srb and Horowitz con- dividual cell is expressed at once in that ity of producing mutations artificially with cluded that normal Neurospora must con- individual. X-rays. When they irradiated some mil- tain gene-controlled enzymes that trans- lions of normal spores of Neurospora, ca- form some simpler materials into ornithine, PACKAGED SPORES pable of synthesizing all their biological ornithine into citrulline, citrulline into ar- In addition to this convenience, Neuro- needs from very simple foods, some were ginine, and so on. If the citrulline-arginine spora is also easy to study genetically be- occasionally damaged in such a way that enzyme were missing because of a dam- cause of the simple, methodical way in they and their descendants needed dietary aged gene, arginine would have to be sup- which the offspring of sexual matings are supplements. Moreover, using techniques plied. But if only the enzyme were missing segregated. If spores of two sexes are that were simple in principle but arduous that produces ornithine out of its raw placed together on a suitable medium, the in practice, they could show that the de- materials, then a supply of ornithine nuclei from each (containing the genes) fective strains of Neurospora were true would be all that was required because the may fuse in sexual union. This results in mutants, i.e., that a gene had been al- other steps in the assembly line were in- a nucleus which contains two sets of genes, tered which caused a heritable defect. In tact. Citrulline or arginine would also en- one from each parent.

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