Gene: An Evolving Concep

Known transcripts Genes

H Genome H N O N

N N H N N N N H O H ncRNA mRNA Unannotated transcripts One gene, Stamen H (male) The first sequence H CH N N O 3 Carpel The rediscovery of Thomas Morgan one enzyme; Francis Crick (female) of a gene, The drafts of N N H N Mendel’s work by Then one gene, N YY yy N COAT_BPMS2, was the human Parent X O Smooth or Generation , Erich one protein. Dented Seeds determined. GENSCAN, a computer genome Green or Yellow Seeds F1 Generation Yy X Yy von Tschermak- The DNase experiment Protein program for gene sequence Green or Yellow pods The nucleic acids Alternative promoters Axial or F2 Generation YY Yy Seysenegg, and by Avery, MacLeod, Terminal Artificial trans- structure prediction, were pub- Flowers Yy yy were isolated and and McCarty suggested The ‘Central Dogma’ The first large-scale Punnett Square mutation of the became available. lished. White or Purple Flowers studied by Friedrich gene function prompted the foun- Studies in Drosophila melano- gene by X-ray transformation is The DNA of molecular biology The ENCODE Project highlighted Miescher. analysis using gene The laws of inheritance dation of . gaster suggest a linear model was reported by induced by DNA. double helix was proposed by the complexity of gene tran- expression in yeast were described. of genes on , Hermann Müller. structure was Francis Crick. scription and regulation. like ‘beads on a string.’ solved.

1865 1869 1900 1910 1927 1941 1944 1953 1958 1972 1994 1997 2001 2007 | | | | | | | | | | | | | | Gene as a discrete unit Gene as a distinct locus Gene as a physical molecule Gene as transcribed code Gene as ORF sequence pattern Gene as annotated genomic entity Gene as a protein blueprint Gene as … ZHENGDONG D. ZHANG MMVII | | | | | | | | | 1909 1913 1928 1952 1961 1965 1977 2003 2007

Griffith’s experi- term invented almost a century ago, ‘gene,’ with The ENCODE The pilot phase of the ENCODE The first appearance Alfred Sturtevant ment demon- Introns and the mechanism of Project was Project was finished. New its beguilingly simple orthography, has become a of the word ‘gene,’ constructed the strating type- The genetic code RNA splicing were discovered by Hershey and launched. gene models are proposed. central concept in biology. Given a speci c meaning derived from the Greek first genetic map. switching in The operon, described was deciphered by Phillip Sharp and Richard Roberts Chase determined at its coinage, this word has evolved into something genesis or genos. pneumococcus by François Jacob and Marshall Nirenberg, demonstrating ‘split gene struc- that DNA is the Jacques Monod, demon- complex and elusive over the years, reecting our suggested a , ture.’ genetic material. strated transcriptional A genomic locus transforming and others. Gene ever-expanding knowledge in genetics and in life sci- 0.0 B control. 1.0 C O principle.

Gly ences at large. e stunning discoveries made in the Glu

Phe Asp Leu Ser U UCAG CAG G U lac Z lac Y lac A A C A Ala C G U Tyr  Project—like many before that signi - 30.7 P U G G U C A C A C A Stop G U

C A U Cys Val G C A

A Protein-coding transcripts

C

G Stop 33.7 R U U G U G

U Trp C

cantly enriched the meaning of this term—are har- G A

Arg A

G G C U

U A C

U

Leu C

G C A A A

G

Ser C

U

A ORF

C U

G C

A

U G A

C

G Pro

U 5’ UTR 3’ UTR

Lys U

G

C

A bingers of another tide of change in our understand- A C G U

Operator Terminator Asn His Alternative splicing Gln

Arg 57.6 M Thr

Met ing of what a gene is. Wilhelm Johannsen Promoter Ile mRNA Novel transcripts lac Operon Alfred Hershey Martha Chase

POSTER DESIGN, ILLUSTRATION, AND TEXT: ZHENGDONG D. ZHANG, . IMAGE CREDITS: THE PORTRAITS OF GREGOR MENDEL AND WILHELM JOHANNSEN ARE USED BY COURTESY OF WIKIPEDIA. THE PORTRAIT OF THOMAS MORGAN IS LICENSED FROM THE CORBIS CORPORATION. THE PHOTOGRAPH OF FRANCIS CRICK AND JAMES WATSON IS COURTESY OF THE JAMES D. WATSON COLLECTION / COLD SPRING HARBOR LABORATORY ARCHIVES. THE PHOTOGRAPH OF ALFRED HERSHEY AND MARTHA CHASE IS COURTESY OF THE COLD SPRING HARBOR LABORATORY ARCHIVES. THE ILLUSTRATION OF MENDEL'S EXPERIMENTS WITH THE PEA PLANT IS GENEROUSLY PROVIDED BY JANE WANG, THE SCIENCE CREATIVE QUARTERLY. THE DRAWINGS OF PROTEIN MOLECULES ARE COURTESY OF IRVING GEIS. THE IMAGE OF THE BACTERIOPHAGE MS2 (PDB ID: 2MS2) IS KINDLY PROVIDED BY DR. JEAN-YVES SGRO, INSTITUTE FOR MOLECULAR VIROLOGY, UNIVERSITY OF WISCONSIN-MADISON. THE DRAWING OF THE DNA DOUBLE HELIX STRUCTURE IS PROVIDED BY THE NATIONAL LIBRARY OF MEDICINE. THE ENCODE PROJECT LOGO IS USED WITH PERMISSION FROM THE NATIONAL HUMAN GENOME RESEARCH INSTITUTE.