【正文】 mation in the Drosophila embryo (NussleinVolhardsome cases, the way in which these plexes andpathways areutilized inthe development and physiology and Weischaus, 1980). Nevertheless, the lossoffunction approach quickly reaches a pragmatic limit for sevof the organism are also conserved. For example, it isknown that intracellular protein transport in yeast and eral reasons. First, the majority of genes have no easilyassayable lossoffunction phenotype. Second, evensynaptic vesicle release in neurons have conserved protein ponents (Rothman, 1994). In signaling path when a phenotype is observed, it only reflects that partof the function of a gene that cannot be pensatedways such as those involving the Ras and Notch cascades, many of the protein ponents are conserved by other genes and pathways. In many cases this willrepresent only a small fraction of the function of a genebetween yeasts, flies, worms, and humans (Wassarmanet al., 1995。 Burns et al., 1994。least two different places or times during development.However, it isnot safeto assumethat whenever a protein Goodrich et al., 1996). However, neither the order northe rate of assembly can be derived by puter analyis expressed in a cell, it is expressed there for functionalreasons。 Mulvihill, 1995。 Thomas, 1993。 and from a mutagenesis analysis of the t regionand result in the death of the organism prior to adulthood. To determine the extent of pensation, we first of chromosome 17 (Dove, 1987). Of the 263 knockouts,approximately 25% are embryonic lethals. Taken at facesummarize dataon Drosophila genes whose inactivationleads to lethality and then pare the fly data with value, these figures indicatethat therewould be approximately 18,000 lethal loci if the mouse genome housedthose from other organisms.The number of lethal loci in the Drosophila genome 70,000 genes. However, this is a highly selected sampleof genes and the extent to which it is a reliable guideis thought to be about 5000 (NussleinVolhard, 1994。 richia coli indicate that 46% of its 4100 genes are recognizable as gene duplicates (Koonin et al., 1995). In yeast,Collins, 1995). Although over 270,000 human expressedReview523Table 2. Frequencies of Lethal Loci in Different Regions of the Drosophila Genome Expressed in Terms of the Number of PolyteneBands in the Mutagenized IntervalExtrapolationNumber of Number of Ratio of Bands of Lethal LociChromosome Bands Analyzed Lethal Loci to Lethal Loci per GenomeX 450 298 33502 415 267 32603 343 235 34704 50 34 3440Total 1253 836 3380Most Intensively Studied Regions on the X ChromosomeX 373 265 3600The 27 individual chromosomal intervals analyzed and the references on which these estimates are based are available from . or.the published genomic sequences show that at least The estimates for Caenorhabditis range from 2,900 to3,500 lethal loci in a genome of approximately 14,00014% of its 5800 genes are clear duplicates. In worms,flies, mice, and humans, there are insufficient data as yet genes (Table 3). These estimates are based on extrapolations from three regions of the worm genome thatto determine what proportion of genes are duplication majorityof genes inthe mouse and human together constitute about 8% of the geic map (Clarket al., 1988。 Fraser et al., 1995。 Miklos, 1993a。 the utility ofestimated the coding capacity of the 115 Mb partgene transfer methods that allow precisely controlledment in three ways. First, we determined the lengths ofmisexpression of genes。Cell, Vol. 86, 521–529, August 23, 1996, Copyright ?1996 by Cell PressThe Role of the Genome Project Reviewin Determining Gene Function:Insights from Model OrganismsGeorge L. Gabor Miklos* and Gerald M. Rubin?freeliving alga Cyanidioschyzon merolae (Maleszka,1993), we have estimated that there will be approxi*The Neurosciences Institute10640 John Jay Hopkins Drive mately 5000 genes if the gene density in this singlecelled alga is similar to that in yeast. In the singlecelledSan Diego, California 92121?Department of Molecular and Cell Biology protozoan Oxytricha similis, there are about 12,000genes (John and Miklos, 1988).Howard Hughes Medical InstituteUniversity of California, BerkeleyBerkeley, California 947203200Eukaryotes of Very Different OrganizationalComplexity, such as Protozoa, Caenorhabditis,and Drosophila, Have Similar Gene NumbersIntroductionin the 12,000 to 14,000 RangeLarge amounts of data, from DNA sequences to onIn D. melanogaster, previous estimates of gene numberline brain atlases, are rapidly accumulating in publicrange from 8,000 to 20,000 (Lewin, 1994。 geneposable elements (John and Miklos, 1988). We haveregulatory dynamics in different systems。 John and Miklos, 1988。 Fleischmann et al., 1995。 Dujon, 1996.data that was originally based on an average mRNA size sequence tags (ESTs)were available in publicdatabasesas of October, 1995, it is still unclear how many genesof 1250 nt (Levy and Manning, 1981). The appropriatehave been identified by this methodology (Jordan, 1996).mRNA length estimated from current molecular data isOn the basis of presently available data, the human2100 nt (Maroni, 1994, 1996), leading to a revised estigenome could have fewer than 50,000 or more thanmate of 10,000 transcription units. Since the two most100,000 genes. This uncertainty isunlikely to beresolvedreliable estimates based on cloned material vary fromuntil a large sample of the genome has been sequenced11,000 to about 13,000 transcription units, we takeso that the fraction of genes represented in the EST12,000 as a working figure for the number of proteindatabases can be assessed.coding genes in D. melanogaster.Why are mammals likely to have four to six times asA parison with other organisms reveals that amany genes as Caenorhabditis and Drosophila? Oneunicellular protozoan