A Dictionary of Genetics phần 10 pptx

Sanger and eight colleagues report the complete nucleotide sequence for the DNA genome of bacteriophage phiX174.. Reddy and eight colleagues publish the complete nucleotide sequence fors

I Zaenen and four colleagues discover the tumor-inducing plasmid of thecrown gall bacterium.

K M Murray and N E Murray manipulate the recognition sites for restrictionendonucleases in lambda (λ) bacteriophage so that its chromosome can be used

as a receptor site for restriction fragments from foreign DNAs Lambda thusbecomes a cloning vehicle

A Tissieres, H K Mitchell, and U M Tracy find that heat shocks result in

the synthesis of six new proteins in Drosophila These are also synthesized by

tissues that do not have polytene chromosomes

B Dujon, P P Slonimski, and L Weill propose a model for recombination

and segregation of mitochondrial genomes in Saccharomyces cerevisiae

Accord-ing to it, mtDNA molecules are present in the zygote cell in multiple copies.These pair at random, and during any mating cycle a segment from one parentcan exchange with that from a second parent mtDNA yielding recombinantunits

R D Kornberg proposes that chromatin is built up of repeated structural units

of 200 base pairs of DNA and two each of the histones H2A, H2B, H3, andH4 These structures, which are later called nucleosomes, are isolated by

M Noll A L Olins, and D E Olins publish the first electron micrographs ofchromatin spreads from nuclei that show nucleosomes

B Ames develops a rapid screening test for detecting mutagenic and possiblycarcinogenic compounds

S Brenner describes methods for inducing, isolating, and mapping mutations

in the nematode Caenorhabditis elegans.

R W Hedges and A E Jacob discover in E coli that ampicillin-resistance genes

can be transferred between plasmids that show no DNA homology The agent

responsible is a mobile DNA sequence, which they named a transposon.

J Ott invents the first computer program (LIPED) for the efficient tion of lod scores

computa-C A Hutchison and three colleagues demonstrate the maternal inheritance ofmitochondrial DNA in horse-donkey hybrids

G L Stebbins publishes Flowering Plants: Evolution Above the Species Level,

which brings a modern framework of cytogenetics and systematics to the study

Molecular biologists from around the world meet at Asilomar, California, towrite a historic set of rules to guide research in recombinant DNA experi-ments

The NIH Recombinant DNA Committee issues guidelines aimed at eliminating

or minimizing the potential risks of recombinant DNA research

L L Goldstein and M S Brown demonstrate that normal fibroblasts havebinding sites for low-density lipoproteins, whereas fibroblasts from humans ho-mozygous for the hypercholesterolemia gene lack these receptors

M Grunstein and D S Hogness develop the colony hybridization method for

the isolation of cloned DNAs containing specific DNA segments or genes

A T C Carpenter identifies recombination nodules in Drosophila

melanogas-ter She points out the correlation between the number of RNs and the number

of meiotic exchanges

D Pribnow determines the nucleotide sequences of two independent

bacterio-phage T7 promoters, and compares these and other known promoter sequences

to form a model for promoter structure and function

E M Southern describes a method for transferring DNA fragments from

agar-ose gels to nitrocellulagar-ose filters The filters are subsequently hybridized to

ra-dioactive RNA and the hybrids detected by autoradiography

W D Benton and R W Davis describe a rapid and direct method for

screen-ing plaques of recombinant lambda bacteriophages that involves transfer of

phage DNA to a nitrocellulose filter and detection of specific DNA sequences

by hybridization to complementary labeled nucleic acids

F Sanger and A R Coulson develop the “plus and minus” method for

deter-mining the nucleotide sequences in DNA by primed synthesis with DNA

poly-merase

M C King and A C Wilson point out that 99% of the proteins that have

been studied in humans and chimpanzees have identical amino acid sequences

They conclude that the biological differences between these two species must

be largely the result of mutations that involve regulatory rather than structural

genes

G Morata and P A Lawrence show in Drosophila that the engrailed mutation

allows cells of the posterior wing compartment to mix with those of the

ante-rior compartment Therefore, the normal allele of this gene functions to define

the boundary conditions between the sister compartments of the developing

wing

B Mintz and K Illmensee inject XY diploid cells from a malignant mouse

teratocarcinoma into mouse blastocysts that then are transferred to foster

mothers Cells derived from the carcinoma appear in both somatic and germ

cells of some F1males When these are mated, some F2mice contain marker

genes from the carcinoma The experiments demonstrate that the nuclei of

teratocarcinoma cells remain developmentally totipotent, even after hundreds

of transplant generations during which they functioned in malignant cancers

S L McKenzie, S Henikoff, and M Meselson isolate mRNAs for heat-shock

proteins and show that they hybridize to specific puff sites on the Drosophila

polytene chromosomes

L H Wang and three colleagues locate within the RNA genome of the Rous

sarcoma virus the segment responsible for its oncogenic activity

G Blobel and B Dobberstein put forth the signal hypothesis

R Dulbecco, H Temin, and D Baltimore receive Nobel Prizes for their studies

on oncogenic viruses

1976 H R B Pelham and R J Jackson describe a simple and efficient

mRNA-dependent in vitro translation system using rabbit reticulocyte lysates.

W Fiers and 11 colleagues complete their analysis of MS2 RNA This is the

first virus to have its genome sequenced from beginning to end

R V Dippell shows in Paramecium that kinetosomes contain RNA (not DNA)

and that RNA (not DNA) synthesis accompanies kinetosome reproduction

N Hozumi and S Tonegawa demonstrate that the DNA segments coding forthe variable and constant regions of an immunoglobulin chain are distant fromone another in the chromosomes isolated from mouse embryos, but the seg-ments are adjacent in chromosomes isolated from mouse plasmacytomas Theyconclude that somatic recombination during the differentiation of B lympho-cytes moves the constant and variable gene segments closer together

W Y Kan, M S Golbus, and A M Dozy are the first to use recombinantDNA technology in a clinical setting They develop a prenatal test for alphathalassemia utilizing molecular hybridization techniques

P M Nurse, P Thuriaux, and K Nasmyth elucidate the genetic control of the

cell division cycle in Schizosaccharomyces pombe Among the genes that control

mitosis are those that encode cyclin-dependent kinases

M F Gellert and three colleagues discover DNA gyrase to be the enzyme thatconverts a relaxed, closed, circular DNA molecule into a negatively supercoiledform

W Y Chooi shows that ferritin-labeled antibodies raised against proteins lated from rat ribosomes) bind to the terminal knobs of fibers extending from

(iso-Miller trees (isolated from the ovarian nurse cells of Drosophila) This

observa-tion proves that Miller trees are rRNA transcripobserva-tion units and shows that atleast some ribosomal proteins attach to a precursor rRNA molecule before itstranscription is completed

B G Burrell, G M Air, and C A Hutchison report that phage phiX174contains overlapping genes

Formal guidelines regulating research involving recombinant DNA are issued

by the National Institutes of Health in the United States

H Boyer and R Swanson found Genentech, an event which marks the ning of the biotech industrial revolution

begin-A Efstratiadis and three colleagues are the first to enzymatically generate

eu-karyotic gene segments in vitro They synthesize double-stranded DNA

mole-cules that contain the sequences transcribed into the mRNAs for the alpha andbeta chains of rabbit hemoglobin

J T Finch and A Klug propose that the 300 A˚ threads seen in electron graphs of fragmented chromatin are formed by the folding of DNA-nucleo-some filaments into solenoids

micro-L H Miller and three colleagues conclude that the Duffy blood group antigens(Fya and Fyb) serve as receptors for the merozoites of Plasmodium vivax and that individuals of blood group Fy−/Fy−are resistant to P vivax infections be-

cause their red cells lack these receptors

1977 A Knoll and E S Barghoorn find microfossils which they interpret as ing cell division in rocks 3,400 million years old This discovery pushes backthe age of life on earth to the lower Archean eon

undergo-J B Corliss and R D Ballard aboard Alvin, a deep-diving minisubmarine,

dis-cover communities of hyperthermophilic bacteria, tube worms, clams, andother organisms, living in the Galapagos rift

E M Ross and A G Gilman show that adenylcyclase is regulated by a proteinthat binds GTP This G protein is purified three years later and shown to be aheterotrimer

K Itakura and six colleagues chemically synthesize a gene for human

somato-statin and express it in E coli This leads to the commercial production of the

first artificial human protein, somatostatin

S M Tilghman and eight colleagues clone the first protein-encoding gene

(mouse beta-hemoglobin) using bacteriophage lambda as a vector

C Jacq, J R Miller, and G G Brownlee describe the presence of

“pseudo-genes” within the 5S DNA cluster of Xenopus laevis oocytes.

J C Alwine, D J Kemp, and G R Stark prepare diazobenzyloxymethyl

(DBM) paper and describe methods for transferring electrophoretically

sepa-rated bands of RNA from an agarose gel to the DBM paper Specific RNA

bands are then detected by hybridization with radioactive DNA probes,

fol-lowed by autoradiography Since this method is the reverse of that described

by Southern (1975) in that RNA rather than DNA is transferred to a solid

support, it has come to be known as “northern blotting.”

F Sanger and eight colleagues report the complete nucleotide sequence for the

DNA genome of bacteriophage phiX174

E W Silverton, M A Navia, and D R Davies determine the

three-dimen-sional structure of the human immunoglobulin molecule

M Leffak, R Grainger, and H Weintraub show that “old” histone octamers

remain intact during DNA replication and that “new” octamers consist entirely

of proteins synthesized immediately before replication

C Woese and G E Fox conclude from their studies of the nucleotide

se-quences of the 16S rRNAs of certain newly discovered microorganisms that

they should be placed in a domain separate from the other bacteria (the

R J Roberts and P A Sharp lead groups that discover split genes in adenovirus

2 R-loop mapping by L Chow and S Berget shows the position of intron

loops Intervening noncoding segments are then described for genes that encode

animal proteins, namely, the rabbit beta-globin gene (A Jeffreys and R A

Flavell) and the chicken ovalbumin gene (R Breathnach, J L Mandel, and

P Chambon)

J Weber, W Jelinek, and J E Darnell report that alternative splicing of

non-consecutive DNA segments in the adenovirus-2 genome can produce multiple

mRNAs

J F Pardon and five colleagues use neutron contrast matching techniques to

demonstrate that in nucleosomes the DNA segment that attaches to the

his-tone octamer is on the outside of the particle

J Sulston and H R Horvitz work out the postembryonic cell lineages for

Caenorhabditis elegans.

J Collins and B Holm develop cosmids for cloning large DNA fragments

F Lee and C Yanofsky explain the mechanism of attenuation that takes place

in the tryptophan operon of E coli.

R S Yalow receives a Nobel Prize for developing the radioimmunoassay

proce-dure

1978 R M Schwartz and M O Dayhoff compare sequence data for a variety ofproteins and nucleic acids from an evolutionarily diverse assemblage of pro-karyotes, eukaryotes, mitochondria, and chloroplasts Their computer-gener-ated evolutionary trees identify the times during evolution when protoeukaryo-tic organisms entered into symbiosis with mitochondria and chloroplasts (about

2 and 1 billion years ago, respectively)

W Gilbert coins the terms intron and exon.

T Maniatis and seven colleagues develop a procedure for gene isolation, whichinvolves construction of cloned libraries of eukaryotic DNA and screening theselibraries for individual sequences by hybridization to specific nucleic acidprobes

M S Collett and R L Erickson report that the product of the src gene of the

Rous sarcoma virus is a protein kinase

W Bender, R Spierer, and D Hogness describe a method for sequencing genes

they call chromosome walking.

E B Lewis concludes that the component genes in the bithorax complex have related functions in Drosophila segmentation and that they evolved from a

smaller number of ancestral genes by their duplication and subsequent ization

special-C Coulondre and three colleagues show that sites in the DNA of E coli

identi-fied as mutational hot spots contain the modiidenti-fied pyrimidine, sine

5-methylcyto-V B Reddy and eight colleagues publish the complete nucleotide sequence forsimian virus 40 and correlate the sequence with the known genes and mRNAs

of the virus

Y W Kan and A M Dozy demonstrate the value of using ment-length polymorphisms as linked markers for the prenatal diagnosis ofsickle-cell anemia

restriction-frag-C A Hutchison and five colleagues demonstrate that it is possible to introducespecific mutations at specific sites in a DNA molecule

E H Blackburn and J G Gall demonstrate that telomeres from Tetrahymena pyriformis consist of short DNA sequences (one strand containing AACCCC,

the other TTGGGG) repeated tandemly 30 to 70 times

R T Schimke and three colleagues show that cultured mouse cells exposed tomethotrexate develop resistance by amplifying the genes that encode the en-zymes that serve as the target for the drug

W Arber, H O Smith, and D Nathans share the Nobel Prize in Physiology

or Medicine for the development of techniques utilizing restriction ases to study the organization of genetic systems

endonucle-P D Mitchell receives the Nobel Prize in Chemistry for his contribution tothe understanding of biological energy transfer through the formulation of thechemiosmotic theory

1979 J G Sutcliffe determines the complete 4,362 nucleotide pair sequence of theplasmid cloning vector pBR322

J C Avise, R A Lansman, and R O Shade successfully use restriction nucleases to measure mitochondrial DNA sequence relatedness in natural pop-ulations

endo-The National Institutes of Health relax guidelines on recombinant DNA to

allow viral DNA to be studied

S Perdix-Gillot reports giant nuclei that are over 1 million–ploid in the cells

of the silk gland of Bombyx mori.

B G Barrell, A T Bankier, and J Drouin report that the genetic code of

human mitochondria has some unique, nonuniversal features

E F Fritsch, R M Lawn, and T Maniatis determine the chromosomal

arrange-ment and structure of human globin genes utilizing recombinant DNA

tech-nology

J R Cameron, E Y Loh, and R W Davis discover transposable elements in

yeast

N Wexler and a group of Venezuelan colleagues begin a study of natives who

are living in three fishing villages on the shore of Lake Maracaibo Huntington

disease is prevalent in this population, and eventually an eight-generation

pedi-gree is constructed that contains over 11,000 people Analyses of DNA samples

of this group lead to the localization and eventual sequencing of the HD gene

by MacDonald and coworkers in 1993

D V Goeddel and nine colleagues construct a gene that encodes human

growth hormone (HGH) using recombinant DNA technology The synthesized

gene is expressed in E coli under the control of the lac promoter and a

polypep-tide having the properties of HGH is synthesized

M R Lerner and J A Steitz report the discovery of small nuclear

ribonucleo-proteins (snurps)

1980 L Olsson and H S Kaplan produce the first human hybridomas that

manufac-ture a pure antibody in laboratory culmanufac-ture

A Hershko, A Ciechanover, I A Rose, and three other colleagues

demon-strate that proteins destined to be destroyed undergo ATP-dependent

conjuga-tion to a specific protein (APF-1) They later show that APF-1 is ubiquitin and

that it delivers doomed proteins to the 26S proteasome where they are broken

down into short peptides for reuse

The United States Supreme Court rules that genetically modified

microorgan-isms can be patented General Electric, on behalf of A Chakrabarty, obtains a

patent for a genetically engineered microorganism capable of consuming oil

slicks

D Lowe describes stromatolites from the Archean of Western Australia They

contain 3.8 billion-year-old fossils that resemble cyanobacteria

J W Gordon and four colleagues produce the first transgenic mice by direct

injection of cloned DNA into the pronucleus of a fertilized egg

M R Capecchi describes a technique for efficient transformation of cultured

mammalian cells by direct microinjection of DNA into cells with glass

micropi-pettes

C Woese and 10 colleagues publish the secondary structure for 16S ribosomal

RNA

D Botstein and three colleagues describe the method of using restriction

frag-ment length polymorphisms to construct genetic linkage maps of the human

genome

W F Doolittle and C Sapienza and, independently, L E Orgel and F H C.Crick point out that the genomes of all species are littered with DNA segmentsthat contribute nothing to the fitness of the species and persist only becausethey are efficient replicators These authors name this collection of DNA seg-

ments selfish DNA and suggest that these DNAs represent the ultimate

para-sites

H Gronemeyer and O Pongs demonstrate that, in Drosophila melanogaster

sali-vary glands, beta ecdysone binds directly to sites on polytene chromosomeswhere ecdysone-inducible puffs occur

C Nu¨sslein-Volhard and E Wieschaus describe the isolation and

characteriza-tion of zygotic segmentacharacteriza-tion mutacharacteriza-tions of Drosophila melanogaster.

L Clark and J A Carbon clone the gene that corresponds to the centromere

of yeast chromosome 3

A R Templeton provides a new theoretical framework for speciation by thefounder effect

Nobel Prizes in Physiology and Medicine go to G D Snell, J Dausset, and

B Benacerraf for their contributions to immunogenetics

P Berg, W Gilbert, and F Sanger receive Nobel Prizes in Chemistry for theircontributions to the experimental manipulation of DNA

1981 R C Parker, H E Varmus, and J M Bishop demonstrate that the tumorigenic

properties of the Rous sarcoma virus are due to a protein encoded by the v-src gene Cells from various vertebrates contain a homologous gene, c-src The two genes differ in that v-src has an uninterrupted coding sequence, whereas c-src

contains seven exons separated by six introns

L Margulis publishes Symbiosis in Cell Evolution Here she summarizes the

evidence for the theory that organelles such as mitochondria, chloroplasts, andkinetosomes evolved from prokaryotes that lived as endosymbionts in the an-cestors of modern-day eukaryotes

R Lande proposes a new model of speciation based on sexual selection onpolygenic traits This model results in a revival of interest in sexual selection

J D Kemp and T H Hall transfer the gene of a major seed storage protein(phaseolin) from beans to the sunflower via a plasmid of the crown gall bacte-

rium Agrobacterium tumefaciens, creating a “sunbean.”

T R Cech, A J Zaug, and P J Grabowski report the discovery of a

self-splicing rRNA in Tetrahymena thermophila This is the first demonstration that

a macromolecule other than a protein can act as a biological catalyst

W F Anderson and three colleagues determine the three-dimensional

struc-ture of the cro repressor at 2.8 A˚ resolution

G Hombrecher, N J Brewin, and A W B Johnson demonstrate that the

ability of Rhizobium bacteria to nodulate legumes and fix atmospheric nitrogen

is due to plasmid-linked genes

P R Langer, A A Waldrop, and D C Ward develop a procedure for sizing biotinylated DNA probes that hybridize normally with complementaryDNA, providing an anchor for streptavidin-linked, color-generating systems

synthe-S Anderson and 13 colleagues work out the complete nucleotide sequence andgenetic organization of the human mitochondrial genome

H Sakano and three colleagues discover two segments in the heavy chain

im-munoglobulin gene of the mouse, which serve as recognition sites for a somatic

DNA recombinase

M E Harper and G F Saunders demonstrate that single-copy genes can be

mapped on human mitotic chromosomes utilizing an improved in situ

hybrid-ization technique

J Banerji, S Rusconi, and S Schaffner show that the transcription of the

beta-globin gene is enhanced hundreds of times when this gene is linked with certain

SV40 nucleotide sequences that they name “enhancer sequences.”

J G Gall and four colleagues localize histone mRNAs that are being

tran-scribed on the lampbrush chromosomes of salamander oocytes

M Chalfie and J Sulston identify among the touch-insensitive mutants of

Caenorhabditis elegans five genes that affect a specific set of six sensory

neu-rons

K E Steinbeck and three colleagues demonstrate that the resistance of a weed,

Amaranthus hybridus, to triazine herbicides is controlled by a chloroplast gene

that encodes a polypeptide to which the herbicide binds Resistant strains of

the weed produce a modified gene product that fails to bind triazine

J D Walker sequences the eight genes of the E coli atp operon These encode

the protein subunits of ATP synthase

1982 Eli Lilly and Company markets a Genentech-licensed, recombinant, human

in-sulin This is the first product generated by this new technology

E P Reddy and three colleagues report that the genetic change that leads to

the activation of an oncogene carried by a line of human bladder carcinoma

cells is due to a single base substitution in this gene The result is the

incorpora-tion of valine instead of lysine in the 12th amino acid of the protein encoded

by the oncogene

P Goelet and five colleagues determine the complete nucleotide sequence for

the RNA genome of the tobacco mosaic virus

P M Bingham, M G Kidwell, and G M Rubin show that P strains of

Dro-sophila contain 30 to 50 copies per genome of a transposable P element This

is the cause of hybrid dysgenesis Then A C Spradling and Rubin demonstrate

that cloned P elements, when microinjected into Drosophila embryos, become

integrated into germ-line chromosomes and that P elements can be used as

vectors to carry DNA fragments of interest into the Drosophila germ line.

E R Kandel and J G Schwartz utilize the gill-withdrawal reflex in Aplysia to

study the molecular control of memory formation They eventually show that

the long-term facilitation of sensory neurons requires the activation of

cAMP-responsive memory genes

S B Prusiner shows that the infectious agent that causes scrapie is a protein,

which he calls a prion

A Klug receives the Nobel Prize for his contributions to the analysis of

crystal-line structures of biological importance, especially virus particles, tRNA, and

nucleosomes

1983 E A Miele, D R Mills, and F R Kramer construct the first recombinant

RNA molecule by inserting a synthetic foreign deca-adenylic acid into a variant

of the RNA genome of phage Q beta via the action of the Q beta replicase

H J Jacobs and six colleagues report the presence of promiscuous DNA in thesea urchin.

T Hunt and four colleagues demonstrate that sea urchin eggs contain a nal mRNA which encodes a protein that is synthesized after fertilization and

mater-is cyclically destroyed and resynthesized during cleavage divmater-isions They name

the protein cyclin.

I S Greenwald, P W Sternberg, and H R Horvitz demonstrate that the

lin-12 mutant of Caenorhabditis functions as a developmental control gene.

M Oren and A J Levine isolate and identify a cDNA of the p53 mRNA from

a SV-40-transformed mouse cell line

S D Gillies and three colleagues show that a tissue-specific enhancer is located

in the first intron of the heavy-chain immunoglobulin gene

W Bender and seven colleagues sequence genes in the bithorax complex of sophila and show that spontaneous mutations by bx, Ubx, and bxd are associ-

Dro-ated with insertions of transposable elements

M P Scott and six colleagues sequence another group of segment identity

genes and work out the organization of the Antennapedia locus.

G N Godson and four colleagues clone the gene that encodes the

circumspo-rozoite protein of Plasmodium knowlesi, and they show that the protein

con-tains a repetitive epitope that serves as a decoy to the host immune system

C Guerrier-Takada and four colleagues show that ribonuclease P consists ofone protein and one RNA subunit and that the latter is the catalytic subunit

L Montagnier in France and R Gallo in the United States lead teams thatindependently publish accounts of the discovery of the virus that causes AIDS

M Kimura and T Ohta estimate 1.8× 109years as the time of divergence

of eukaryotes and prokaryotes through comparative studies of the nucleotidesequences of 5S rRNAs from humans, yeasts, and bacteria

M Rassoulzadegan and six colleagues isolate a recombinant DNA clone fromthe polyoma virus that immortalizes cultured fibroblast cells from rat embryos.They also show that only the amino-terminal portion of the protein encoded

by the viral gene carries the immortalizing function

R F Doolittle and six colleagues demonstrate that the simian sarcoma virus

oncogene, v-sis, is derived from the gene encoding a platelet-derived growth

factor

E Hafen, M Levine, and W J Gehring work out a technique for in situ

hy-bridization of labeled DNA probes to RNA transcripts in frozen tissue sections.They succeed in localizing transcripts of homeotic genes to specific regions of

developing Drosophila embryos.

R Mann, R C Mulligan, and D Baltimore genetically engineer the Moloneymurine leukemia virus so that it can be used safely as a vector in gene transferexperiments with mammalian hosts

B McClintock receives the Nobel Prize for her discovery of transposable netic elements

ge-1984 D C Schwartz and C R Cantor show that pulsed field gradient sis can be used to separate DNA fragments as large as 2,000 kbp This methodovercomes the limitation of agarose gel electrophoresis, which can only sepa-rate molecules of much smaller sizes (50 kbp or less)

electrophore-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 Ko¨hler, 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

1985 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 nique and point out its potential use in forensic science.

tech-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 HawaiianDrosophilidae that the evolution of this group is driven by sexual selectionwhich ensures the choice of mates with the greatest Darwinian fitness

M S Brown and J L Goldstein receive the Nobel Prize for identifying thelow-density lipoprotein receptor pathway and for demonstrating that familialhypercholesterolemia is a genetic defect in this pathway

1986 M.-C Shih, G Lazar, and H M Goodman show that the nuclear genes thatencode chloroplast glyceraldehyde-3-phosphate dehydrogenase of higher plantsare direct descendants of the genes from the symbionts that gave rise to thechloroplast 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 sands of times faster, and the Human Genome Project is greatly facilitated

thou-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 hemoglobin genes can be experimentally substituted for defective thalassemiagenes in the mouse They inject cloned normal genes into the fertilized thalas-semic eggs The mice that develop possess red blood cells that can synthesizenormal beta-hemoglobin chains These transgenic mice transmit this ability totheir offspring

beta-J Nathans, D Thomas, and D S Hogness isolate and characterize the humanvisual 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 genesoften contain multiple conserved domains and suggests that genes which shareone or more of these domains form networking families that program the earlydevelopment 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 chromosomesfrom chloroplasts is determined for two plant species In the case of the liver-

wort, Marchantia polymorpha, the genome contains 121 kilobase pairs (K ama and 12 colleagues), while the genome of tobacco, Nicotiana tabacum, con-

Ohy-tains 155 kilobase pairs (K Shinozaki and 22 colleagues) Some chloroplastgenes 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

1987 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 Frohnho¨fer, 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

1988 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 leucinezipper and propose that it functions as a DNA binding site

W Herr and 10 colleagues discover a new DNA-binding domain (POU) coded by a family of homeotic genes Many POU genes are expressed only inthe nervous system

en-R en-R Brown and seven colleagues clone the human androgen receptor geneand show that mutations within it cause the hereditary androgen insensitivitysyndrome

D C Wallace and seven colleagues report that a human, maternally inheriteddisease, 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 acomplete 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 encyclopedicliterature 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 sity receives the patent for “oncomice,” developed by P Leder and T Stewart

Univer-S L Mansour, K R Thomas, and M R Capecchi describe a general strategyfor gene targeting in the laboratory mouse

1989 W Driever and C Nu¨sslein-Volhard show that in Drosophila the protein coded by the bicoid gene acts by switching on the hunchback segmentation gene.

en-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 sophila polytene chromosomes The sites include the Antennapedia complex and the bithorax complex, which contain genes known to be repressed by Pc.

Dro-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 act with a known protein

inter-J inter-J Brown and three colleagues determine the structure of the “Dotted” poson of maize

trans-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 aminoacid sequence of the protein it encodes, and determine the nature of its mostcommon 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 cedure for identifying mutations in selected DNA sequences

pro-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

1991 S M Simon and G Blobel demonstrate that translocons in the endoplasmicreticulum 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 Hawaiiansilverswords with those of North American tarweeds and conclude that speciesfrom two genera of California tarweeds are the closest living relatives of theHawaiian silverswords

L Buck and R Axel report the cloning and characterization of 18 differentgenes from a multigene family of about a thousand genes which encode odorantreceptors 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 bythe 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 bandq13 of human chromosome 2, which mark the site of telomere-telomere fu-sions that converted two rod-shaped ancestral chromosomes into the V-shapedchromosome 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 anexpanded CGG triplet in patients suffering from fragile X–associated mentalretardation

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

1992 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

1993 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 mutamuta-tions 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 membrane conductance regulator functions as a channel capable of conductingmultiple anions They show that positively charged amino acids in the sixthmembrane helix of the transmembrane domains of the CFTR protein are re-quired for halide transport.

trans-R J Roberts and P A Sharp receive the Nobel Prize in Medicine for ing split genes

discover-M Smith and K B Mullis receive the Nobel Prize in Chemistry for inventingthe site-directed mutagenesis technique and the polymerase chain reaction, re-spectively

1994 N Morral and 30 colleagues from 19 European laboratories study the ellites associated with the∆F508 mutation in the cystic fibrosis genes of CFfamilies from various parts of Europe They conclude that the mutation origi-nated in southwestern Europe at least 50,000 years ago

microsat-D E Nilsson and S Pelger show from a computer simulation that an organsimilar in complexity to a fish eye can evolve from a patch of skin containingphotosensitive cells in a relatively short time (⬃400,000 generations)

M Chalfie and three colleagues demonstrate that green fluorescent proteinscan 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 byDNA analysis

S E Gabriel and four colleagues find a positive correlation between theamount of cystic fibrosis conductance regulator protein in intestinal cells andthe 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 lacktelomerase 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 tion during movement of the chromosomes

posi-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 thesize 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 alsooccurs 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 entiremitochondrial genomes of three individual women (Japanese, European, andAfrican) and females belonging to four species of apes The analysis supportsthe theory that all human mtDNA molecules are derived from a woman wholived 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 scribed in the hypothalamus

tran-M Moritz, Y Zheng, B Alberts, and five colleagues identify containing ring complexes in centrosomes and show that they function as mi-crotubule nucleating sites

gamma-tubulin-E B Lewis, gamma-tubulin-E Wieschaus, and C Nu¨sslein-Volhard receive the Nobel Prize inMedicine for their analyses of the genetic mechanisms that control cell differen-

tiation during embryogenesis and metamorphosis in Drosophila.

1996 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 gal infections

fun-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, showthat a homeobox protein can control translation by binding to discrete targetsequences on specific mRNAs

J G Lawrence and J R Roth propose the selfish operon model to explain theevolution of gene clusters in bacteria

M Lewis and seven colleagues determine the crystalline structure of lactoseoperon repressor proteins complexed with operator DNA or inducer

A Goffeau and 15 colleagues publish “Life with 6,000 Genes,” a review of thestructure 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 availablefor 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 ture of mitochondrial ribosomal proteins that the mitochondria in all eukary-otes have a monophyletic origin

struc-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 tists and land plants

protoc-B A Krizek and E M Meyerowitz present a model that explains the mations brought about by homeotic mutations during the development of the

transfor-Arabidopsis flower.

1997 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

1998 S T Cole and 41 coworkers sequence the DNA of Mycobacterium tuberculosis

and work out its genetic structure

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 16SRNAs 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 habiditis.

Caenor-R W Frenck, E H Blackburn, and K M Shannon show for peripheral 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 gradualduring the period from 25 to 80

leuko-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 tis and investigate its genetic structure They conclude that the species contains

trachoma-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 brush morphology

lamp-W B Whitman, D C Coleman, and lamp-W J Wiebe estimate the total number

of prokaryotes on earth to be 4–6× 1030 cells Their calculations show thatprokaryotes are the largest living reservoir of C, N, and P

1999 K Petren, B R Grant, and P R Grant work out the phylogeny of Darwin’sfinches 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 existswhose transcription rates are dramatically induced or repressed as ploidy levelsrise

J D Evans and D E Wheeler demonstrate that, during the larval tion of genetically identical female honeybees into worker or queen castes, dif-ferent sets of specific genes are switched on or off

differentia-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 mission of genes from archaeons

trans-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

2000 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

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

D R Davies and three colleagues report the three-dimensional structure ofTn5 transposase complexed with the recognition sequences that terminate thetransposon, and they propose a mechanism for transposition that involves asynaptic 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 thevariation 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 types from 70 to 378

pheno-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 Easternnon-Jewish populations share a common pool of Y-chromosome markers

B Korber and nine colleagues present evidence that HIV-1 emerged fromchimpanzees about 70 years ago

R S Singh and R J Kulathinal propose a sex gene pool theory of speciationapplicable 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 nition of long-term memory

defi-2001 M M Yusupov and six colleagues determine the three dimensional structure

of the bacterial 70S ribosome at 5.5A˚ resolution The ribosomes are from aspecies 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 ent genes associated with virulence

differ-H Tettelin and 38 colleagues sequence the genome of Streptococcus pneumoniae

and assign functions to many of the coding sequences contained in its DNAmolecule

R Pawliuk and 13 colleagues use a genetically engineered lentivirus as an RNAvector 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

2002 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

2003 H T Skaletsky and 39 colleagues sequence the male-specific region of thehuman Y chromosome and describe the organization of its heterochromaticand 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 thatconversion to the prion-like state plays a role in the maintenance of synapticchanges 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 medius Mutations in a gene that controls the syntheses of yellow or black mela-

inter-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 homologous1.75 mbp stretches of DNA from humans and chimpanzees The segmentscontain the major histocompatibility complexes Unexpectedly, the majority ofthe evolutionary sequence divergence between the two primates is found to bedue 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 ofschedule 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, thechannels that facilitate the movement of water molecules through cell mem-branes

2004 G W Tyson and nine colleagues use community genome sequencing to mine the genomes and metabolic interrelations of archaean species flourishing

deter-in a toxic acid pool at the bottom of a mdeter-ine shaft

J C Venter and 22 colleagues use community genome sequencing on the karyotes filtered out of a 1,500 liter sample of surface water from the SargassoSea They sequence 1.05 billion base pairs of DNA representing 1.2 milliongenes from an unknown number of marine species Approximately 800 of thegenes encode light sensitive proteins

pro-M Matsuzaki and 41 colleagues sequence the genome of Cyanidioschyzon lae and determine its functional morphology This red alga has the smallest

mero-genome of all photosynthetic eukaryotes

G Rice and eight colleagues study the tertiary and quaternary structures of thecoat proteins of certain dsDNA viruses that attack species of Archaea, Bacteriaand Eukaryotes They demonstrate conformational similarities in these proteinsand conclude that these viruses evolved from a common ancestor that livedprior to the formation of the three domains of cellular life

E Birney, M Clamp, and R Durbin publish the algorithms GeneWise andGenomewise which are widely used in studies of comparative evolutionary ge-nomics

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

2005 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

Here we arrange alphabetically the names of scientists credited with

vari-ous discoveries and the years key papers by them were published In

situa-tions where a research contribution made at a later time is referred to in

an earlier entry, both years are given Thus, Benda, 1890 (1898) indicates

that his 1898 publication is referred to in an 1890 entry (on Altmann’s

bioblasts) If two or more publications by the same author are cited for the

same year, the number of entries appears in parentheses, for example,

Ja-cob, F., 1961(3) The list also contains an entry for Nobel Prizes Here

one can find the years when awards were given to geneticists and

molecu-lar biologists.

Atwood, K C., 1966Abelson, J., 1969

Avery, A G., 1937Adams, M D., 2000

Avise, J C., 1979Air, G M., 1976

Allen, M K., 1964

Baeckeland, E., 1959Allison, A C., 1954

Bailey, W T., 1946Alquist, J E., 1984

Bakalara, N., 1990Altman, S., 1971, 1989

Baker, S J., 1990Altmann, R., 1890

Balbiani, E G., 1881Alwine, J C., 1977

Baldauf, S L., 1993Ambros, V., 1984

Ballard, R D., 1977Ames, B., 1974

Baltimore, D., 1970, 1971, 1975, 1983Amici, G B., 1830

Bankier, A T., 1979Ammermann, A., 1969

Barany, F., 1990Anderson, J E., 1987

Bargiello, T A., 1984Anderson, S G., 1998

Barrell, B G., 1965, 1976, 1979Anderson, W A., 1966

Barter, R H., 1967Anderson, W French, 1990

Bateson, W., 1900, 1906Anfinsen, C B., 1961, 1973

Bauer, H., 1934Anzai, T., 2003

558

Beaton, M J., 1999 Bragg, W L., 1913, 1915

Breathnach, R., 1977Beatty, B R., 1969

Brent, L., 1953Beermann, W., 1952, 1961

Bridges, C B., 1914, 1915, 1917, 1921, 1923, 1925,Bell, A C., 2000

Briggs, R., 1952Belyaeva, E S., 1998

Benacerraf, B., 1963, 1972, 1980 Britten, R J., 1959, 1966, 1968

Brown, D D., 1964, 1968, 1972(2)Benda, C., 1890 (1898)

Brown, J J., 1989Benne, R., 1986

Brown, R., 1831Benton, W D., 1975

Benzer, S., 1955, 1961, 1969, 1971, 1998 Brown, R H., 1987

Brown, T R., 1988Berg, P., 1972, 1980

Brownlee, G G., 1965, 1977Bernstein, F., 1925

Bult, C., 1996Berson, S A., 1957

Burgess, R., 1969Berzelius, J J., 1838

Burnet, F M., 1959, 1960Bestor, T H., 1997

Burrell, B G., 1976Bhattacharyya, M K., 1990

Bu¨tschli, O., 1876Biessmann, H., 1990

Billingham, R E., 1953

Cairns, J., 1963Bingham, P M., 1982

Callaerts, P., 1995Birnbaumer, L., 1970

Callan, H G., 1958Birney, E., 2004

Camerarius, J R., 1694Birnstiel, M L., 1966, 1967, 1969

Cameron, J R., 1979Bishop, J M., 1981, 1989

Campbell, A M., 1962Bittner, J J., 1936

Cann, R L., 1987Blackburn, E H., 1978, 1985, 1998

Cantor, C R., 1984Blake, C C F., 1967

Capecchi, M R., 1980, 1988Blakeslee, A F., 1904, 1920, 1922, 1930, 1934,

Cappecchi, M., 19661937

Carbon, J A., 1980Blattner, F R., 1997

Carle, G F., 1987Blobel, G., 1975, 1991, 1999

Carpenter, A T C., 1975Blum, B., 1990

Carr, D H., 1965Boeke, J D., 1985

Carr, N G., 1972Boivin, A., 1948

Carrier, W L., 1964Bollag, R J., 1994

Carson, H L., 1985Bolton, E T., 1963

Caspar, D L D., 1959Bonaccorsi, S., 1993

Caspersson, T., 1936, 1941, 1970Bonner, D., 1944

Castle, W E., 1905 (1910)Bonneville, M A., 1963

Catteruccia, F., 2000Bookstein, R., 1990

Cavalier-Smith, T., 1999Boon, C., 1969

Cech, T R., 1981, 1989(2)Botstein, D., 1980

C elegans Sequencing Consortium, 1998

Boveri, T., 1887, 1888, 1902, 1914

Chada, K., 1986Boyce, R P., 1964

Chain, E., 1940, 1945Boycott, A E., 1923

Chakrabarty, A., 1980Boyer, H W., 1972, 1976

Chalfie, M., 1981, 1994Boyer, P D., 1973, 1997

Chambon, P., 1977Brachet, J., 1941

Chaplin, G., 2000Bragg, W H., 1913, 1915

Chapman, V., 1958 Dausset, J., 1954, 1980

Davidson, E H., 1968Chargaff, E., 1950

Davies, D R., 1977, 2000Chatton, E., 1937

Davis, M., 1984Chetverikov, S S., 1926

Dawid, I B., 1968Che`vremont-Comhaire, S., 1959

Debergh, P., 1973Chikashige, Y., 1994

de Graff, R., 1657Chison, J A., 1972

De Jonge, P., 1989Chow, L., 1977

Dellweg, H., 1961Cieciura, S J., 1956

d’Herelle, F., 1917Clark, A J., 1965

Dintzis, H., 1961Clark, L., 1980

Diver, C., 1923Clausen, R E., 1925, 1926

Dobzhansky, T., 1936, 1937, 1944Cleland, R E., 1930

Domagk, G., 1939Cohen, J E., 1985

Doolittle, R., 1983Cohen, S N., 1972, 1973

Doty, P., 1960Coleman, D C., 1998

Dressler, D., 1968Collins, F S., 1984, 2001

Driever, W., 1988, 1989Coons, A H., 1941

Dubnau, J., 1996Corey, R B., 1951

Dujon, B., 1974Cornefert, F., 1960

Dunham, I., 1999Costantini, F., 1986

du Toit, A L., 1927Coulson, A R., 1975

Creech, H J., 1941

Earle, W., 1940Creighton, H B., 1931

East, E M., 1913Crick, F H C., 1952, 1953, 1958, 1961, 1962,

Edelman, G M., 1959, 1969, 1972

1966, 1980

Edgar, R S., 1966Crippa, M., 1968

Edwards, R G., 1968Cue´not, L., 1905

Efstratiadis, A., 1976Egolina, N A., 1972D’Agostino, S E., 2003

Eichinger, L., 2005Dalton, A J., 1954

Elgin, S C R., 1986Daneholt, B., 1972

Ellis, E L., 1939Dareste, C., 1874

El-Sayed, N M., 2005Darnell, J E., 1971, 1977

Ephrussi, B., 1935, 1949 Gallo, R., 1983

Galton, F., 1869, 1875, 1889Erickson, R L., 1978

Gardner, M J., 2002Evans, J D., 1999

Garrod, A E., 1909Ewing, M., 1956

Grunberg-Manago, M., 1955 Hoekstra, H E., 2003

Hoffman, E P., 1987Grunstein, M., 1975

Hogness, D S., 1975, 1978, 1986Gulick, J J., 1872

Gurdon, J B., 1962, 1964, 1967, 2004 Holley, R W., 1965, 1968

Holliday, R., 1964Guthrie, R., 1961

Holt, R A., 2002

Inman, R B., 1970Hennig, W., 1950

Consor-tium, 2001, 2003Herr, W., 1988

Ishida, M R., 1963Hershey, A D., 1946, 1949, 1952, 1961, 1969

Ivanovsky, D I., 1892Hertwig, O., 1875

Hess, O., 1968

Jablonski, N G., 2000Hiaga, A., 1970

Jackson, D A., 1972Hickmans, E H., 1954

Jackson, R J., 1976Hilschmann, N., 1965

Jacob, F., 1955, 1958, 1961(3), 1963, 1965Hoagland, M B., 1955

Jacobs, P A., 1959 Kleckner, N., 1997

Klenk, E., 1935Jacobson, C B., 1967

Klenow, H., 1971James, T C., 1986

Knight, T A., 1822–24Janssen, Z., 1590

Knapp, E., 1939Jeffreys, A., 1977

Knoll, M., 1932Jelinek, W., 1977

Koch, R., 1877, 1882, 1883, 1905Jerne, N K., 1955, 1984

Kohne, D E., 1968, 1972Johansson, C., 1970

Ko¨lliker, A., 1841Johnson, A.W B., 1981

Ko¨lreuter, J G., 1761–67Johnson, R T., 1970

Konopka, R J., 1971Jones, R N., 1941

Kornberg, A., 1956, 1959, 1961, 1967Josse, J., 1961

Kossel, A., 1884

Lai, C S L., 2001Keeney, S., 1997

Lamarck, J B de Monet, 1809Kelner, A., 1949

Lande, R., 1981Kemp, J D., 1981

Landsteiner, K., 1900, 1901, 1930Kermicle, J L., 1970

Lansman, R A., 1979Khorana, H G., 1967, 1968, 1970

Laveran, A., 1880, 1904, 1907Kihara, H., 1923

Lawrence, J G., 1996, 1997Kim, S H., 1973

Lazar, G., 1986King, M C., 1975

Lederberg, E M., 1951, 1952Kipnis, C., 1985

Lee, F., 1977Klebs, T A E., 1860