APPENDIX C: CHRONOLOGY
J. Gitschier and eight colleagues report the cloning of the gene encoding the antihemophilic factor in humans. C. G. Sibley and J. E. Ahlquist show from DNA-DNA hybridization data that humans are more closely related to chimpanzees than to any other hominoid and estimate that the species diverged 5 or 6 million years ago. R. F. Pohlman, N. V. Fedoroff, and J. Messing determine the nucleotide se- quence of the maize transposable element Activator. F. S. Collins and four colleagues identify mutations upstream of the gamma- globin gene that cause it to be switched on in adults. W. McGinnis and six colleagues discover and name the conserved homeobox sequence in Drosophila homeotic genes, and they find that the mouse also con- tains genes that influence segmentation and possess homeoboxes. J. C. W. Shepherd and four colleagues show that yeast mating-type regulatory proteins contain homeoboxes. T. A. Bargiello and M. W. Young clone and sequence period, the first gene known to control a biological clock. M. Davis and T. Mak identify and clone the genes for the T cell receptor. N. K. Jerne, G. Kohler, and C. Milstein receive the Nobel Prize in Medicine for their contributions to immunology. R. B.
Merrifield is awarded a Nobel Prize in Chemistry for his work in auto- mated peptide synthesis. J. R. Miller, A. D. McLachlan, and A. Klug report the isolation and character- ization of a zinc finger protein from Xenopus oocytes. This protein binds to the 5S RNA gene and controls its transcription. M. P. Williamson, T. F. Havel, and K. Wu¨thrich publish the first atomic resolu- tion structure of a protein, a bull seminal proteinase inhibitor, using nuclear magnetic resonance spectroscopy. The universal code theory has to be amended because codons that serve as termination signals according to the “universal” genetic code are found to en- code amino acids in certain ciliates and bacteria. For example, in Stylonychia lemnae UAA and UGA encode glutamine (S. Horowitz and M. A. Gorowsky) and in Mycoplasma capricolum UGA encodes tryptophan (F. Yamao). C. M. Newman, J. E. Cohen, and C. Kipnis demonstrate mathematically that the punctuated shifting equilibrium patterns of species formation seen in the fossil record are to be expected on traditional grounds and do not require spe- cial mechanisms to explain them. C. W. Greider and E. H. Blackburn isolate a telomerase from Tetrahymena pyriformis. O. Smithies and four colleagues report the successful insertion of DNA se- quences into human tissue culture cells by homologous recombination at the beta-globin locus. This is an early example of transfection. J. D. Boeke and three colleagues discover the first retroposons in Saccharo- myces. S. M. Mount and G. M. Rubin determine the complete nucleotide sequence of a Drosophilia copia element and conclude that it is a retroposon. A. J. Jeffries, V. Wilson, and S. L. Thien develop the DNA fingerprint tech- nique and point out its potential use in forensic science. R. K. Saiki, K. B.
Mullis, and five colleagues report the use of the polymerase chain reaction to allow enzymatic amplification in vitro of specific beta-hemo- globin gene fragments. H. L. Carson concludes from a study of the ecological genetics of the Hawaiian Drosophilidae that the evolution of this group is driven by sexual selection which ensures the choice of mates with the greatest Darwinian fitness. M. S. Brown and J. L. Goldstein receive the Nobel Prize for identifying the low-density lipoprotein receptor pathway and for demonstrating that familial hypercholesterolemia is a genetic defect in this pathway. M.-C. Shih, G. Lazar, and H. M. Goodman show that the nuclear genes that encode chloroplast glyceraldehyde-3-phosphate dehydrogenase of higher plants are direct descendants of the genes from the symbionts that gave rise to the chloroplast. Later during evolution, these genes were transferred from the chlo- roplast to the nuclear genome. L. E. Hood and three colleagues invent the first automated DNA sequencer. As these machines are perfected, the sequencing of genomes becomes thou- sands of times faster, and the Human Genome Project is greatly facilitated. T. C. James and S. C. R. Elgin identify HP1 (heterochromatin protein 1) in Drosophila melanogaster. A.
Tomlinson and D. F. Ready report the discovery of sevenless, a mutation in Drosophila that controls the developmental fate of a specific cell in the omma- tidium. A. G. Amit and three colleagues determine the three-dimensional structure of an antigen-antibody complex at a resolution of 2.8 A˚. F. Costantini, K. Chada, and J. Magram demonstrate that cloned normal beta- hemoglobin genes can be experimentally substituted for defective thalassemia genes in the mouse. They inject cloned normal genes into the fertilized thalas- semic eggs. The mice that develop possess red blood cells that can synthesize normal beta-hemoglobin chains. These transgenic mice transmit this ability to their offspring. J. Nathans, D. Thomas, and D. S. Hogness isolate and characterize the human visual pigment genes. M. Noll and four colleagues identify a gene (paired) that encodes a protein with a DNA-binding site (the paired domain). This domain is later identified in mammalian regulatory proteins. Noll’s group shows that regulatory genes often contain multiple conserved domains and suggests that genes which share one or more of these domains form networking families that program the early development of multicellular organisms. R. Benne and five colleagues discover RNA editing in trypanosomes. H. M. Ellis and H. R. Horvitz isolate genes in Caenorhabditis elegans that cause the programmed death of specific cells.
The complete nucleotide sequence and gene organization of the chromosomes from chloroplasts is determined for two plant species. In the case of the liver- wort, Marchantia polymorpha, the genome contains 121 kilobase pairs (K. Ohy- ama and 12 colleagues), while the genome of tobacco, Nicotiana tabacum, con- tains 155 kilobase pairs (K. Shinozaki and 22 colleagues). Some chloroplast genes are found to contain introns. E. U. Selker and three colleagues characterize the phenomenon of repeat- induced point mutation (RIP) in Neurospora. V. F. Semeshin and five colleagues observe new bands and interbands at the site where a transposable element had inserted into a Drosophila polytene chro- mosome. R. Levi-Montalcini and S. Cohen receive the Nobel Prize in Physiology for their studies on growth factors. E. Ruska receives the Nobel Prize in Physics for designing the first electron microscope. M. R. Kuehn and four colleagues introduce a human gene into the mouse to allow its study in a convenient laboratory rodent. They employ a mutant allele of the gene encoding HPRT and use a retrovirus as a vector to insert it into cultured mouse embryonic germ cells.
These are then implanted into mouse embryos to form chimeras. Strains of mice carrying the human gene are ob- tained from these chimeras. C. Nu¨sslein-Volhard, H. G. Frohnhofer, and R. Lehmann show that a small group of maternal effect genes exist in Drosophila that determine the polarized pattern of development of the embryo. E. P. Hoffman, R. H. Brown, and L. M. Kunkel isolate dystrophin, the protein encoded by the musculardystrophy locus. D. C. Wiley and five colleagues determine the three-dimensional structure of HLA-A2, a human class I histocompatibility molecule. D. C. Page and eight colleagues clone a segment of the human Y chromosome that contains a gene which encodes a factor influencing testis differentiation. Within the Y chromosome fragment is a 1.2 kb ORF that appears to encode a zinc finger protein. R. L. Cann, M. Stoneking and A. C. Wilson compare the extent of sequence divergence in the mtDNA of individuals belonging to geographically distinct human populations. They erect a genealogical tree that suggests that all mtDNAs can be traced back to a common African maternal ancestor. C. J. O’Kane and W. J.
Gehring successfully utilize enhancer traps to identify the positions in Drosophila embryos of elements that are functioning to activate the transcription of specific genes. D. T. Burke, G. F. Carle, and M. V. Olson describe a technique for cloning large segments of exogenous DNA by means of yeast artificial chromosomes. R. E. Dewey, D. H. Timothy, and C. S. Levings show that cytoplasmic male sterility in maize is due to a protein encoded by the mitochondrial genome. K. H. Wolf, W. H. Li, and P. M. Sharp report for various plant species that the rates of nucleotide substitutions in chDNAs are on average five times slower than the rates shown for nuclear genes. J. E. Anderson, M. Ptashne, and S. C. Harrison describe the three-dimensional structure of the lambda (λ) bacteriophage repressor-operator complex. S. Tonegawa wins the Nobel Prize for his elucidation of the genetic mechanism that generates antibody diversity. W. Driever and C. Nu¨sslein-Volhard demonstrate that the bicoid gene encodes a protein that is distributed in an exponential concentration gradient along the anteroposterior axis of the embryo. P. M. Macdonald and G. Struhl show that a 625-nucleotide segment in the trailer of a message encoded by the maternal polarity gene bicoid is responsible for the anterior localization of this mRNA in the Drosophila oocyte. W. H. Landschulz, P. F. Johnson, and S. L. McKnight discover the leucine zipper and propose that it functions as a DNA binding site. W. Herr and 10 colleagues discover a new DNA-binding domain (POU) en- coded by a family of homeotic genes. Many POU genes are expressed only in the nervous system. R. R. Brown and seven colleagues clone the human androgen receptor gene and show that mutations within it cause the hereditary androgen insensitivity syndrome. D. C. Wallace and seven colleagues report that a human, maternally inherited disease, Leber’s hereditary optic neuropathy, is caused by a mutation in mito- chondrial DNA. H. H. Kazazian and five colleagues discover two cases of hemophilia A due to insertions of truncated transposable elements.
They subsequently isolate a complete transposable element that is a likely progenitor of one of these inser- tions. They show the transposon resides on chromosome 22 and that homolo- gous elements occur in chimpanzee and gorilla at the same genomic location. This finding suggests that the element has been occupying the same chromo- somal site since the evolutionary divergence of humans, chimpanzees, and go- rillas 7 million years ago. V. Sorsa publishes a two-volume monograph that reviews the encyclopedic literature concerning polytene chromosomes and presents electron microscope maps of Drosophila salivary-gland chromosomes. The first U.S. patent is issued for a genetically altered animal. Harvard Univer- sity receives the patent for “oncomice,” developed by P. Leder and T. Stewart. S. L. Mansour, K. R. Thomas, and M. R. Capecchi describe a general strategy for gene targeting in the laboratory mouse. W. Driever and C. Nu¨sslein-Volhard show that in Drosophila the protein en- coded by the bicoid gene acts by switching on the hunchback segmentation gene. B. Zink and R. Paro show by immunostaining that a protein encoded by the Polycomb (Pc) gene binds to a limited number of discrete sites along the Dro- sophila polytene chromosomes. The sites include the Antennapedia complex and the bithorax complex, which contain genes known to be repressed by Pc. S. Field and O. Song develop the yeast two-hybrid system for identifying pro- tein-protein interactions, based on the properties of the GAL4 protein of S. cerevisiae. This system is later modified by various lab groups as a screen to identify protein sequences encoded by genomic or cDNA libraries which inter- act with a known protein. J. J. Brown and three colleagues determine the structure of the “Dotted” trans- poson of maize. L. H. Hartwell and T. A.
Weinert introduce the concept of controls called “checkpoints” that ensure the order of events in the cycle of cell division. L.-C. Tsui and 24 colleagues identify the cystic fibrosis gene, predict the amino acid sequence of the protein it encodes, and determine the nature of its most common mutant allele. M. Srivastava and four colleagues clone and sequence the cDNA for human nucleolin. J. R. Williamson, M. K. Raghuraman, and T. R. Cech present the guanine quar- tet model of telomere structure. D. B. Kaback, H. Y. Steensma, and P. De Jonge show that crossing over on the shortest chromosome of yeast is two times higher than the average for the whole genome. They conclude that this ensures that at least one crossover will occur in every bivalent, a necessity for proper segregation of the homlogs dur- ing the first meiotic division. Y. Q. Qian and five colleagues show that the Antennapedia homeobox protein binds to DNA through a helix-turn-helix motif. F. D. Hong and seven colleagues determine the structure of the retinoblastoma gene. The RB transcript is encoded in 27 exons dispersed over about 200 kilo- base pairs of genomic DNA. M. Horowitz and five colleagues determine the structure of the human gluco- cerebrosidase gene. They also sequence a nearby pseudogene. Mutations in the functional gene are the cause of Gaucher disease. J. M. Bishop and H. E. Varmus receive the Nobel Prize in Medicine for their studies on the oncogenes of retroviruses. T. R. Cech and S. Altman receive the Nobel Prize in Chemistry for their dem- onstration that certain RNAs have enzymatic functions. 1990 W. French Anderson describes the first successful example of human gene ther- apy. Lymphocytes from a four-year-old girl suffering from adenosine deaminase deficiency are grown in culture and later incubated with a retroviral vector carrying a normal gene that encodes the missing enzyme. The transformed cells are reinjected into the patient, where they multiply and correct the disease. M. K. Bhattcharyya and four colleagues show that one of the mutations (Wrin- kled seed) used by G. Mendel in his classic experiments is due to the insertion of a transposon in a gene encoding an enzyme that controls the starch content of pea embryos. S. J. Baker and four colleagues show that the introduction of wild-type p53 genes suppress the proliferation of human cancer cells. R. Bookstein and four colleagues show that cells from some human prostate cancers contain mutated retinoblastoma genes and that the uncontrolled growth of these cells is suppressed when wild-type RB alleles are introduced into them. B. Blum, N. Bakalara, and L. Simpson propose that RNA editing is performed by guide RNA molecules. R. N. Van Gelder and five colleagues devise a method for amplifying RNA utilizing an RNA polymerase from bacteriophage T7. B. G. Herrmann and four colleagues clone the T complex, which is required for the formation of mesoderm in the mouse. F. Yamamoto and four colleagues work out the molecular basis of the ABO blood group system. J. Malicki, K. Schughart, and W. McGinnis introduce a homeobox gene from the mouse into Drosophila embryos and observe that it can induce homeotic transformations similar to those produced by the Antennapedia gene.
There- fore, genes from animals that have been evolving independently for hundreds of millions of years generate products that function interchangeably. D. Malkin and 10 colleagues show that the defects underlying the Li-Fraumeni syndrome are mutations in the p53 gene. Subsequent studies reveal that p53 mutations are present in about half of all human cancers. F. Barany invents the ligase chain reaction. This provides a rapid screening pro- cedure for identifying mutations in selected DNA sequences. X. Fang and three colleagues clone the gene in Plasmodium vivax that encodes its Duffy receptor. H. Biessmann and six colleagues show that a specific retrotransposon can trans- pose to the broken ends of Drosophila chromosomes and “heal” them. M. A. Oettinger and three colleagues identify RAG-1 and RAG-2, genes whose products catalyze V(D)J recombination. P. M. Kane and five colleagues discover protein splicing in yeast. S. M. Simon and G. Blobel demonstrate that translocons in the endoplasmic reticulum contain aqueous pores through which proteins manufactured on ri- bosomes pass from the cytoplasm to the ER lumen. G. M. Preston and P. Agre isolate the cDNA for aquaporin-1. B. G. Baldwin and three colleagues compare the chloroplast DNAs of Hawaiian silverswords with those of North American tarweeds and conclude that species from two genera of California tarweeds are the closest living relatives of the Hawaiian silverswords. L. Buck and R. Axel report the cloning and characterization of 18 different genes from a multigene family of about a thousand genes which encode odorant receptors in the rat. This is the first report in which odorant receptors are de- scribed and molecularly characterized in any species. M. L. Sogin proposes that the ancestor of eukaryotes was a chimera formed by the fusion of prokaryotes with complementing metabolic capabilities. M. A. Houck and three colleagues suggest that mites may transfer P elements between Drosophila species. D. A. Wheeler, J. C. Hall, and five colleagues succeed in introducing cloned Drosophila simulans period genes into the genomes of D. melanogaster carrying inactive per alleles. Transduced males “sing” the simulans’ song. J. W. Ijdo and four colleagues identify specific nucleotide sequences in band q13 of human chromosome 2, which mark the site of telomere-telomere fu- sions that converted two rod-shaped ancestral chromosomes into the V-shaped chromosome 2 of modern humans. This resulted in a reduction in the number of chromosome pairs to 23 from the 24 pairs characteristic of chimpanzees, gorillas, and orangutans. A. J. M. H.
Verkerk and 20 colleagues identify the FMR-1 gene at the fragile site of the human X chromosome and demonstrate that the gene contains an expanded CGG triplet in patients suffering from fragile X-associated mental retardation. D. R. Knighton and six colleagues determine the three-dimensional structure of the catalytic core shared by all known eukaryotic protein kinases. R. R. Ernst is awarded the Nobel Prize in Chemistry for his contributions to the development of high-resolution nuclear magnetic resonance (NMR) spec- troscopy. G. G. Oliver and 146 colleagues from a consortium of 35 European labora- tories publish the first complete nucleotide sequence for a eukaryotic chromo- some. Chromosome III of Saccharomyces cerevisiae is the third smallest. It is 315,357 bp long and contains 182 ORFs, of which 117 (80%) show no signifi- cant homology to any previously sequenced yeast genes. R. M. Story, I. T. Weber, and T. A. Steitz determine the three-dimensional structure of RecA, a protein playing a central role in crossing over and DNA repair of E. coli. M. C. Rivera and J. A. Lake make phylogenetic studies of the translation elon- gation factors isolated from various prokaryotes and eukaryotes. Comparisons of amino acid sequences identify a subgroup of archaeons as the immediate relatives of eukaryotes and therefore the source of the nucleus. D. Haig proposes the theory of parent-offspring conflict to explain the evolu- tion of parental imprinting. E. G. Krebs and E. H. Fischer receive the Nobel Prize for discovering protein kinases and elucidating their roles in signal transduction. M. C. Mullins and C. Nu¨sslein-Volhard generate hundreds of developmental mutants in the zebra fish, opening a new era in study of the genetic control of vertebrate development. D. R. Rosen, T. Siddique, and 32 colleagues identify 11 different ALS muta- tions in 13 families. The mutations are all in the gene that encodes the SOD enzyme. R. Hallick and seven colleagues determine the complete nucleotide sequence for the DNA of chloroplasts from Euglena gracilis. Some chloroplast genes con- tain twintrons. A. Chaudhuri and five colleagues clone the gene for the Duffy blood group factor. It encodes a 338 amino acid protein that is attached to the erythrocyte plasma membrane and is required for the invasion of certain malaria parasites. S. L. Baldauf and J. D. Palmer conclude from a phylogenetic study of combined sequence data from certain ubiquitous proteins that animals and fungi are each other’s closest relatives. Therefore both animals and fungi have been placed in a monophyletic supergroup, the Opisthokonta. G. Maroni publishes the first atlas of the comparative morphology of the genes of a specific eukaryote. The monograph illustrates 90 Drosophila genes that transcribe mRNAs ranging in size from 319 to 4,749 base pairs. C. Pisano, S. Bonaccorsi, and M. Gatti report that a protein which is not en- coded by Y-linked genes binds to a specific, giant, lampbrush loop on the Y chromosome in Drosophila spermatocytes. This protein is a component of the sperm tail. They suggest that the Y loops in spermatocytes bind exogenous specific proteins and facilitate their assembly into axonemes. L. Pereira and six colleagues determine the organization of the FBNI gene. This encodes fibrillin, and mutations in it cause Marfan syndrome. M. E. MacDonald and 56 colleagues belonging to the Huntington’s Disease Research Group clone and sequence the Huntington disease gene and show that an unstable trinucleotide repeat is expanded in victims of the disease. J. A.
Tabcharani and six colleagues demonstrate that the cystic fibrosis trans- membrane conductance regulator functions as a channel capable of conducting multiple anions. They show that positively charged amino acids in the sixth membrane helix of the transmembrane domains of the CFTR protein are re- quired for halide transport. R. J. Roberts and P. A. Sharp receive the Nobel Prize in Medicine for discover- ing split genes. M. Smith and K. B. Mullis receive the Nobel Prize in Chemistry for inventing the site-directed mutagenesis technique and the polymerase chain reaction, re- spectively. N. Morral and 30 colleagues from 19 European laboratories study the microsat- ellites associated with the ∆F508 mutation in the cystic fibrosis genes of CF families from various parts of Europe. They conclude that the mutation origi- nated in southwestern Europe at least 50,000 years ago. D. E. Nilsson and S. Pelger show from a computer simulation that an organ similar in complexity to a fish eye can evolve from a patch of skin containing photosensitive cells in a relatively short time ( M. Chalfie and three colleagues demonstrate that green fluorescent proteins can be used to visualize sites in cells where specific genes are being expressed. P. Gill and eight colleagues identify the remains of the Romanov family by DNA analysis. S. E. Gabriel and four colleagues find a positive correlation between the amount of cystic fibrosis conductance regulator protein in intestinal cells and the amount of fluid secretion induced by cholera toxin. They propose that cys- tic fibrosis heterozygotes are resistant to cholera, and this selective advantage is responsible for the high frequency of the gene in human populations. W. C. Orr and R. S. Sohal construct transgenic lines of Drosophila bearing extra copies of catalase and superoxide dismutase genes. The aging process is slowed in these flies. N. W. Kim and nine colleagues develop a sensitive assay for telomerase activity. Using it they show that human somatic cells from differentiated tissues lack telomerase activity, whereas cells from a variety of cancers contain active telo- merases.
Normal ovaries and testes also were positive for telomerase activity. Y. Chikashige and six colleagues observe the movement of chromosomes dur- ing meiotic prophase in Schizosaccharomyces pombe by fluorescence micros- copy. They report that the telomeres group together and assume a leading posi- tion during movement of the chromosomes. T. Tully and eight colleagues isolate genes that control the formation of mem- ory in Drosophila. Y. Zhang and five colleagues clone the obese gene of the mouse and determine its structure. The product appears to be a secretory protein that controls the size of the body fat depot. R. J. Bollag and five colleagues demonstrate that the T genes of the mouse encode a protein motif (the T box), which binds to DNA. This T box also occurs in genes with critical roles in the development of amphibians, fishes, and insects. S. Whitham and five colleagues use the maize Activator transposable element to tag and clone a disease-resistance gene in tobacco. Y. Miki and 44 colleagues identify BRCA1, a human anti-oncogene that, when mutated, confers susceptibility to breast and ovarian cancer. D. Arendt and K. Nu¨bler-Jung provide support for the Saint-Hilaire hypothesis of 1822. Their comparative studies of the expression of homologous genes that control the dorsoventral patterning of embryonic cells show that in flies and mice these genes have opposite effects. Dorsalization genes in Drosophila cause ventralization in Mus, whereas genes that cause ventralization in flies specify dorsal patterns in mice. J. B. Clark, W. P.
Maddison, and M. G. Kidwell report phylogenetic studies that show horizontal transfer of P elements has occurred at least twice in the genus Drosophila. M. Rodbell and A. G. Gilman receive a Nobel Prize for discovering G proteins and elucidating their role in cellular signal transduction. 1995 G. Halder, P. Callaerts, and W. J. Gehring demonstrate in Drosophila melano- gaster that the gene eyeless is a master control gene for eye morphogenesis. M. Schena and three colleagues used DNA microarray technology to simulta- neously monitor the expression of 45 different genes in Arabidopsis. The micro- arrays were prepared by high-speed robotic printing of cDNAs on glass. C. Wilson and J. W. Szostak report in vitro evolution experiments which gener- ate RNAs that can catalyze self-alkylation reactions. J. Hughes and seven colleagues publish the sequence of the 4,320 amino acids in polycystin, the product of the PKD1 gene. Mutations in this gene cause polycystic kidney disease in humans. J. Feng and 15 colleagues induce senescence in HeLa cells by adding an anti- sense RNA that contains a message opposite to the templating domain of hu- man telomerase. S. Baxendale and 10 colleagues compare human and puffer fish Huntington disease genes and show that the human gene is over seven times larger because its introns are larger, not its exons. R. Wooster and 40 colleagues identify BRCA2. R. D. Fleischmann, J. C. Venter, and 38 colleagues publish the first complete nucleotide sequence of a free-living organism (Haemophilus influenzae). A few months later, C. M. Fraser, J. C. Venter, and 27 colleagues publish the com- plete nucleotide sequence of Mycoplasma genitalium. R. Sherrington, P. H. St. George-Hyslop, and 31 colleagues isolate and charac- terize a gene on chromosome 14 which is responsible for 80% of the cases of early-onset, familial Alzheimer’s disease. Two months later, G. D. Shellenberg and 21 colleagues report locating a gene on chromosome 1 that encodes a pro- tein showing great similarities in amino acid sequence to the product of the AD gene on chromosome 14.
Mutations in the AD gene on chromosome 1 are responsible for the other 20% of the cases of early-onset, familial AD. The products of these genes are called presenilin 1 and 2. S. Labeit and B. Kolmer clone the cDNA for cardiac titin. This is the largest protein known, some 50 times the size of average proteins. K. Zhao, C. M. Hart, and U. K. Laemmli purify a protein from Drosophila that binds to insulator DNAs and demonstrate by immunostaining that this protein attaches to hundreds of interbands and many puff boundaries on polytene chro- mosomes. S. Horai and four colleagues compare the nucleotide sequences for the entire mitochondrial genomes of three individual women (Japanese, European, and African) and females belonging to four species of apes. The analysis supports the theory that all human mtDNA molecules are derived from a woman who lived in Africa about 140,000 years ago. L. A. Tartaglia and 18 colleagues identify a gene, OB-R, that encodes a leptin receptor and show that the mRNA for this membrane-bound protein is tran- scribed in the hypothalamus. M. Moritz, Y. Zheng, B. Alberts, and five colleagues identify gamma-tubulin- containing ring complexes in centrosomes and show that they function as mi- crotubule nucleating sites. E. B. Lewis, E. Wieschaus, and C. Nu¨sslein-Volhard receive the Nobel Prize in Medicine for their analyses of the genetic mechanisms that control cell differen- tiation during embryogenesis and metamorphosis in Drosophila. G. D. Penny and four colleagues use gene targeting to demonstrate that in order for an X chromosome to undergo inactivation, the Xist gene on that X must be transcriptionally active. B. Lemaitre and four colleagues elucidate the genetic control in Drosophila of the synthesis of different antimicrobial peptides in response to bacterial or fun- gal infections. C. Bult and 39 colleagues show that most of the genes making up the genome of the archaeon Methancoccus jannaschii have no equivalent in other organisms. J. Dubnau and G. Struhl, as well as R. Rivera-Pomar and four colleagues, show that a homeobox protein can control translation by binding to discrete target sequences on specific mRNAs. J. G. Lawrence and J. R. Roth propose the selfish operon model to explain the evolution of gene clusters in bacteria. M. Lewis and seven colleagues determine the crystalline structure of lactose operon repressor proteins complexed with operator DNA or inducer. A.
Goffeau and 15 colleagues publish “Life with 6,000 Genes,” a review of the structure of the yeast genome. The complete nucleotide sequences for all 16 chromosomes of Saccharomyces cerevisiae took the combined labors of 600 sci- entists in North America, Europe, and Japan and is the first genome available for a eukaryote. E. Spanopoulou and five colleagues show that the protein encoded by the RAG-1 gene contains a homeobox through which it binds to lymphocyte DNA during V(D)J recombination. They point out that RAG-1/RAG-2 complexes behave like the transposases of nematodes. G. Burger and three colleagues conclude from a study of the comparative struc- ture of mitochondrial ribosomal proteins that the mitochondria in all eukary- otes have a monophyletic origin. T. Kaneko and 23 colleagues completely sequence the genome of the cyano- bacterium Synechocystis and determine the position of over 3,000 ORFs. Many of these genes are later identified in the chloroplasts of photosynthetic protoc- tists and land plants. B. A. Krizek and E. M. Meyerowitz present a model that explains the transfor- mations brought about by homeotic mutations during the development of the Arabidopsis flower.