4 Apr


F. R. Blattner and 16 colleagues sequence the genome of Escherichia coli and begin to assign functions to its genetic elements. F. Kunst and 150 collaborators publish the complete nucleotide sequence for the genome of Bacillus subtilis and describe its genetic organization. H-P. Klenk and 50 colleagues determine the genome structure of Archaeoglobus fulgidus and compare it to Methanococcus jannashii, the other archaeon for which sequence data are available. There are surprising qualitative differences. Abundant genes that allow protein splicing occur in Methanococcus, but none occur in Archaeoglobus. I. Wilmut and four colleagues report the successful cloning of a mammal. The sheep Dolly has chromosomes derived from a cell of the udder of a pregnant female. Once mature, Dolly gave birth to a healthy lamb. This offspring, how- ever, was the result of a normal mating and gestation. M. Krings and five colleagues are able to isolate and sequence segments of mt- DNA from bones of Neandertal fossils and compare them to homologous seg- ments from modern humans. They conclude that Neandertals constitute a spe- cies distinct from Homo sapiens. J. Summerton and D. Weller describe the design, preparation, properties, and potential uses of Morpholinos, synthetic polymers with antisense characteris- tics. C. F. Fraser and 34 colleagues determine the genomic sequence of the Lyme disease spirochaete, Borrelia burgdorferi. It has a main chromosome that is lin- ear, as are some of its plasmids. F. Yang and three colleagues use chromosome-specific paint probes to demon- strate that the Indian muntjak (2N = 6) has a reduced chromosome number because of the end-to-end fusion of different chromosomes.

For example, its chromosome 3 is an assemblage of seven chromosomes present in the Chinese muntjak (2N = 46). S. Keeney, C. N. Giroux, and N. Kleckner show Spo11 to be a DNA double- strand-break-producing topoisomerase that is responsible for meiotic crossing- over in yeast. J. C. Lawrence and H. Ochman suggest that most bacteria contain mosaic ge- nomes and show that in a species like E. coli, 15-30% of the genome is made up of DNA sequences contributed from other species by horizontal mobile elements. J. A. Yoder, C. P. Walsh, and T. H. Bestor suggest that DNA methylation is a mechanism that evolved to suppress the effects of selfish DNA. D. H. Skuse and nine colleagues present evidence from girls with Turner syn- drome that the X chromosome contains imprinted genes that affect their social behaviors. P. D. Boyer and J. E. Walker share the Nobel Prize in Chemistry for their contributions to the enzymology of ATP synthase. S. B. Prusiner is awarded the Nobel Prize in medicine for his elucidation of the molecular structure of prions. S. T. Cole and 41 coworkers sequence the DNA of Mycobacterium tuberculosis and work out its genetic structure. APPENDIX C: CHRONOLOGY S. G. Anderson and nine colleagues determine the nucleotide sequence of the Rickettsia prowazeki genome and conclude that this parasitic bacterium has un- dergone reductive evolution. They also stress the similarities between the 16S RNAs of mitochondria and these bacteria. The C. elegans Sequencing Consortium, made up of 407 scientists associated with the Sanger Centre in Cambridge, England, and the Washington University of Medicine in St. Louis, Missouri, USA, determine the nucleotide sequence and gene organization for the first multicellular species, the nematode Caenor- habiditis. R. W. Frenck, E. H. Blackburn, and K. M. Shannon show for peripheral leuko- cytes that telomeres shorten as humans age. However, the rate of loss of telo- meric repeats is most rapid during the first four years of life and more gradual during the period from 25 to 80. Y. J. Lin, L. Serounde, and S. Benzer isolate methuselah, a gene that extends the life span of Drosophila, and they subsequently determine the properties of the protein it encodes. M. Lyon proposes that DNA sequences on mammalian X chromosomes, called LINE-1 elements, may interact with XIST RNA to facilitate gene silencing by helping this RNA spread along the chromosome. A.

Fire and five colleagues show that the injection of double-stranded RNA into Caenorhabditis silences specific genes. They call this phenomenon “RNA interference.” R. S. Stephens and 11 colleagues sequence the genome of Chlamydia trachoma- tis and investigate its genetic structure. They conclude that the species contains many genes with phylogenetic origins from eukaryotes. E. S. Belyaeva and five colleagues discover a gene that controls the underrepli- cation of heterochromatin in polytene chromosomes of Drosophila. J. G. Gall and C. Murphy show that demembranated Xenopus sperm heads, when injected into oocyte nuclei from Xenopus or Notophthalmus, swell and liberate their chromosomes, which then take on a transcriptionally active lamp- brush morphology. W. B. Whitman, D. C. Coleman, and W. J. Wiebe estimate the total number of prokaryotes on earth to be 4-6 × 1030 cells. Their calculations show that prokaryotes are the largest living reservoir of C, N, and P. K. Petren, B. R. Grant, and P. R. Grant work out the phylogeny of Darwin’s finches based on microsatellite DNA length variations among the related Gala- pagos species. T. Galitski and four colleagues demonstrate that most genes in Saccharomyces cerevisae continue to be expressed at the same relative levels in yeast strains of different ploidies (1N, 2N, 3N, 4N). However, a small subset of genes exists whose transcription rates are dramatically induced or repressed as ploidy levels rise. J. D. Evans and D. E. Wheeler demonstrate that, during the larval differentia- tion of genetically identical female honeybees into worker or queen castes, dif- ferent sets of specific genes are switched on or off. K. E. Nelson and 28 colleagues determine the genome sequence of Thermotoga maritima.

They conclude that although this hyperthermophile belongs to the bacteria, it has acquired a significant portion of its genome by horizontal trans- mission of genes from archaeons. R. M. Andrews and five colleagues resequence human mtDNAs. They analyze the original DNA sample used by Anderson et al. (1981) and also mtDNA from HeLa cells. They uncover several errors and suggest some simple revisions to correct the Cambridge reference sequence and clarify its position in mtDNA lineages. G. P. Copenhaver and 13 colleagues analyze the centromeres of Arabidopsis thaliana at the nucleotide level and show that they contain genes capable of transcription. M. J. Beaton and T. Cavalier-Smith show for a group of cryptomonad species that differ in cell volumes by a 10-fold factor that nuclear and nucleomorph genome sizes obey different scaling laws. Nuclei in larger cells have more DNA, but nucleomorphs do not. This finding supports the hypothesis that noncoding DNA has a skeletal function in eukaryotic nuclei. O. White and 31 colleagues determine the genome sequence and the genetic organization of the radioresistant bacterium Deinococcus radiodurans R1. I. Dunham and 216 colleagues are the first to sequence a human chromosome. They show that the smallest chromosome (number 22) contains 545 genes spread along a 33.4 mb molecule of DNA. The MHC Sequencing Consortium (consisting of 28 contributors from eight international centers) publishes a map of the gene loci in the human major histocompatibility complex. J. G. Gall and three colleagues demonstrate that many proteins and RNAs that function in the synthesis and posttranscriptional processing of RNAs are assem- bled in Cajal bodies. G.

Blobel receives the Nobel Prize for deciphering the method used by cells to target newly synthesized proteins to the endoplasmic reticulum or other organelles. P. Underhill and an international group of 20 colleagues publish a study of paternal lines of evolutionary descent that they traced by following markers in the DNA of Y chromosomes from humans belonging to ethnic groups from different parts of the world. W. V. Ng and 42 colleagues determine the genome sequence and genetic orga- nization of the archaeon Halobacterium species NRC1. A collaborative, international group of 152 scientists that called itself the Arabi- dopsis Genome Initiative publishes a genome sequence for the first plant, Arabi- dopsis thaliana. They conclude that about 70% of its 25,500 genes are dupli- cated and that the actual number of different genes is less than 15,000. C. Lemieux, C. Otis, and M. Turmel sequence the genome of the chloroplast of the green alga Mesostigma viride. They conclude that this chDNA shows an organization that predates the split between chlorophytes and green plants about 800 million years ago. A. C. Bell and G. Felsenfeld show that CTCF, a DNA-binding protein, serves to insulate an imprintable gene (Igf2) from its enhancer. M. Hattori and 63 colleagues determine the nucleotide sequence of human chromosome 21 and show that it contains only 40% as many genes as chromo- some 22, which is similar in size. F. Catteruccia and six colleagues develop a method for introducing foreign genes into malaria mosquitoes that utilizes the Minos transposon. APPENDIX C: CHRONOLOGY D. R. Davies and three colleagues report the three-dimensional structure of Tn5 transposase complexed with the recognition sequences that terminate the transposon, and they propose a mechanism for transposition that involves a synaptic complex, transposition intermediate that is hairpin shaped. M. D.

Adams and 189 colleagues publish the genome sequence of Drosophila melanogaster euchromatin. They estimate that this genome contains 13,600 structural genes. G. M. Rubin and 54 colleagues publish an analysis of the comparative genomics of yeast, worm, fly, and human that is encyclopedic in scope. They find, for example, that at least 30% of the structural genes of Drosophila have orthologs in Caenorhabiditis. Of 289 genes associated with human diseases, 61% have an ortholog in Drosophila. N. G. Jablonski and G. Chaplin propose a comprehensive theory to explain the variation in human skin color. A. G. Fraser and five colleagues use RNA interference to assign phenotypes to 90% of the genes on chromosome 1 of Caenorhabditis elegans. This technique enables them to increase the number of sequenced genes with known pheno- types from 70 to 378. J. F. Heidelberg and 31 colleagues determine the DNA sequences and the orga- nization of genes within the two chromosomes of the cholera bacterium, Vibrio cholerae. M. F. Hammer and eleven colleagues show that Jewish and Middle Eastern non-Jewish populations share a common pool of Y-chromosome markers. B. Korber and nine colleagues present evidence that HIV-1 emerged from chimpanzees about 70 years ago. R. S. Singh and R. J. Kulathinal propose a sex gene pool theory of speciation applicable to all higher sexual organisms. R. S. Singh then links it to a specia- tion model that also includes asexual organisms and plants. E. Kandel receives the Nobel Prize for his contributions to the molecular defi- nition of long-term memory. M. M.

Yusupov and six colleagues determine the three dimensional structure of the bacterial 70S ribosome at 5.5A˚ resolution. The ribosomes are from a species of thermophilic bacteria. J. J. Ferretti and 22 colleagues sequence the genome of Streptococcus pyogenes and illustrate its genetic structure. They determine the location of the 40 differ- ent genes associated with virulence. H. Tettelin and 38 colleagues sequence the genome of Streptococcus pneumoniae and assign functions to many of the coding sequences contained in its DNA molecule. R. Pawliuk and 13 colleagues use a genetically engineered lentivirus as an RNA vector to integrate a normal human beta hemoglobin gene into the chromo- some of a host. This is a mouse genetically engineered to have defects in beta- chain synthesis. Normal genes are integrated into hematopoetic stem cell chro- mosomes, and the transgenic mouse synthesizes normal levels of hemoglobin. D. W. Wood, E. W. Nester, and 49 colleagues describe the organization of the genome of Agrobacterium tumefaciens C58. C. S. L. Lai and four colleagues isolate and characterize FOXP2, a gene re- quired for the development of language in children. M. Ridanpaa and twelve colleagues show that a hereditary disease of humans cartilage-hair hypoplasia (CHH) is caused by mutations in the RMRP gene. This is the first untranslated nuclear gene that upon mutation is found to cause a human disease. V. V. Kapitonov and J. Jura use an in silico analysis to identify rolling-circle transposons. O. Masden and nine colleagues and W. J.

Murphy and five colleagues use gene sequence data to construct phylogenies for placental mammals. The resulting phylogenetic trees differ substantially from the traditional ones developed from comparative anatomy and fossil data. The International Human Genome Sequencing Consortium, led by F. S. Col- lins and consisting of hundreds of scientists from around the world and J. C. Venter and colleagues at Celera Genomics independently determine the draft sequence of the euchromatic portion of the human genome. Annotated maps of the human genome are published in Nature vol. 409 (Feb. 15 issue) and Science vol. 291 (Feb. 16 issue). L. H. Hartwell, R. T. Hunt, and P. M. Nurse receive the Nobel Prize in Physiol- ogy or Medicine for their discoveries of key chemicals that regulate the cell division cycle. M. J. Gardner and 44 other members of an international consortium success- fully sequence the genome of Plasmodium falciparum, the protozoan causing subtertian malaria, the most dangerous form of the disease. R. H. Holt and 122 other members of an international consortium successfully sequence the genome of Anopheles gambiae, a principal vector of malaria, and analyze the functions of many of the genes uncovered. K. Kondo and four colleagues document the first case of horizontal gene trans- fer between a specific prokaryote (the bacterium Wolbachia) and a specific eukaryote (the beetle Callosobruchus). P. Dehal and 86 colleagues generate a draft sequence of the genome of the ascidian Ciona intestinalis. This was the first Urochordate to have its genome sequenced. X. Huang and three colleagues develop a technique for identifying amplified and overexpressed genes in the chromosomes of cultured human cancer cells.

The first gene identified by this technique is TAOS. Y. Matsuoka and five colleagues identify the oldest surviving teosinte ancestor of corn and conclude that highland farmers started its domestication in south- ern Mexico about 9,000 years ago. S. Aparicio and 40 colleagues present the draft sequence and initial analysis of the genome of Takifugu rubripes. The Nobel Prize in Medicine is awarded jointly to Sydney Brenner, H. Robert Horvitz, and John E. Sulston for their work concerning genetic regulation of organ development and programmed cell death. K. Wu¨thrich shares the Nobel Prize in Chemistry with J. B. Fenn and K. Ta- naka for his contributions to the development of nuclear magnetic resonance spectroscopy as a tool for determining the three-dimensional structure of bio- logical molecules. APPENDIX C: CHRONOLOGY H. T. Skaletsky and 39 colleagues sequence the male-specific region of the human Y chromosome and describe the organization of its heterochromatic and euchromatic elements. K. Si, S. Lindquist, and E. R.

Kandel discover that a neuronal CPEB protein from Aplysia, which regulates protein synthesis at activated synapses, alters its form and behaves like a prion in its biologically active state. They propose that conversion to the prion-like state plays a role in the maintenance of synaptic changes that allow long-term memory storage. M. W. Nachman, H. E. Hoekstra, and S. L. D’Agostino elucidate the molecular genetic mechanisms for adaptive melanism in a desert mouse Chaetodipus inter- medius. Mutations in a gene that controls the syntheses of yellow or black mela- nins produce coat colors that have been selected to provide camouflage for the mice that live in dark- vs light-colored natural environments. J. E. Galagan and 76 colleagues publish a draft sequence for the genome of Neurospora and analyze the structure and functioning of the genetic system revealed. T. Anzai and 21 colleagues compare the nucleotide sequences in homologous 1.75 mbp stretches of DNA from humans and chimpanzees. The segments contain the major histocompatibility complexes. Unexpectedly, the majority of the evolutionary sequence divergence between the two primates is found to be due not to single base substitutions, but to insertions and deletions (indels). The International Human Genome Sequencing Consortium announces the suc- cessful completion of the Human Genome Project, nearly 2 years ahead of schedule. The euchromatic portion of the human genome is completely se- quenced with an error rate of less than 1 per 10,000 bases. P. Agre receives the Nobel Prize in chemistry for discovering aquaporins, the channels that facilitate the movement of water molecules through cell mem- branes. G. W. Tyson and nine colleagues use community genome sequencing to deter- mine the genomes and metabolic interrelations of archaean species flourishing in a toxic acid pool at the bottom of a mine shaft. J. C. Venter and 22 colleagues use community genome sequencing on the pro- karyotes filtered out of a 1,500 liter sample of surface water from the Sargasso Sea. They sequence 1.05 billion base pairs of DNA representing 1.2 million genes from an unknown number of marine species. Approximately 800 of the genes encode light sensitive proteins. M.

Matsuzaki and 41 colleagues sequence the genome of Cyanidioschyzon mero- lae and determine its functional morphology. This red alga has the smallest genome of all photosynthetic eukaryotes. G. Rice and eight colleagues study the tertiary and quaternary structures of the coat proteins of certain dsDNA viruses that attack species of Archaea, Bacteria and Eukaryotes. They demonstrate conformational similarities in these proteins and conclude that these viruses evolved from a common ancestor that lived prior to the formation of the three domains of cellular life. E. Birney, M. Clamp, and R. Durbin publish the algorithms GeneWise and Genomewise which are widely used in studies of comparative evolutionary ge- nomics. APPENDIX C: CHRONOLOGY S. Simonsson and J. G. Gurdon show that DNA demethylation is necessary for the nuclear reprogramming of Xenopus somatic cells. R. Axel and L.

Buck share the Nobel Prize in Medicine for their discoveries of odorant receptors and the molecular basis for odor recognition. The Nobel Prize in Chemistry is awarded to A. Ciechanover, A. Hershko, and I. Rose for their discovery of ubiquitin-mediated protein degradation. M. T. Ross and 284 colleagues (representing 21 institutions in 6 countries) publish the DNA sequence of the human X chromosome and a discussion of its organization and evolution. L. Eichinger together with an international group of 95 scientists sequence the genome of the slime mold Dictyostelium discoideum, analyze its repertoire of genes and proteins, and determine its position in the evolutionary tree of eu- karyotes. S. Richards and 51 colleagues sequence the genome of Drosophila pseudoob- scura and compare the order of its genes to that of Drosophila melanogaster. They identify a core set of about 10,000 genes that have been conserved since the divergence of the two species 25-50 million years ago. Three international teams of scientists sequence and compare the genomes of three trypanosomatid parasites, which cause major diseases in millions of peo- ple in many regions of the developing world. M. Berriman et al. sequence and analyze the genome of Trypanosoma brucei, N. M. El-Sayed et al. of Trypano- soma cruzi, and A. C. Ivens et al. of Leishmania major. These studies provide insights into the biology of these parasites and information crucial for the devel- opment of new therapeutic drugs. R. L. Lamason and 24 colleagues show that golden, a pigmentation mutation first observed in the zebrafish, identifies SLC 24A5, the gene responsible for the skin color differences between African and European human populations.

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