外文翻译-基因组计划在决定基因功能中的角色：来自模式生物的洞察英文-外文文献(编辑修改稿)

外文翻译-基因组计划在决定基因功能中的角色：来自模式生物的洞察英文-外文文献(编辑修改稿)内容摘要：

of genes are duplication majorityof genes inthe mouse and human together constitute about 8% of the geic map (Clarket al., 1988。 Howell and Rose, 1990。 Johnsen and Baillie,genomes exist as multigene families, some of whosememberships are in the hundreds to thousands. It is 1991).In S. cerevisiae, approximately 900 genes out of 5800estimated that there are 2020 or so protein kinases andperhaps as many as 1000 phosphatases (Hunter, 1995). are cell lethals, and an additional 900 act to stop cellcycle processes or cause impairment of growth on speThis pares with an estimated 350 protein kinasesand 80 phosphatases in the worm (Hodgkin et al., 1995). cific media (Burns et al., 1994). Hence about 1800 genesin toto are equivalent to the lethal class of multicellularHowever, if mammalian genomes are minimally octoploid, then a substantial proportion of the mouse and organisms (Table 4).In Arabidopsis there are approximately 500 lethalhuman genomes will, initially at least, have consisted ofduplication products. Anecdotal data on an increasing genes (Meinke, 1994) in a genome that is reported tohouse about 25,000 genes (Goodman et al., 1995).number of genes support this view: Drosophila has onecopy each of the Ras, Raf, and Notch genes, as well as Whether this finding is a peculiarity of plant reproductiveprocesses and embryonic development or whether theof the genes of the Hox cluster, while vertebrates havethree or more of each of these genes. current estimates for the number of lethal genes or totalgene number are unreliable ones (or both) awaits futureIn multicellular organisms, functional duplicate copiesof a gene can exist in a genome, but if their expression analysis.In the zebrafish, it is estimated that there are roughlypatterns do not overlap, their products are unable topensate for each other if either gene is mutated. 5000 lethal genes (Haffter et al., submitted), althoughthe total number of genes in the genome is not information gathered in databases will provide anessential guide to analyzing the extent of potential The only estimate of gene number in a teleost is fromthe pufferfish Fugu rubripes, which is claimed to havepensation during the life cycle of an organism by providing detailed information on the sites of expression of as many genes as humans (Brenner et al., 1993), although this estimate is based on a sample of only %each gene.of the genome.In Mus, the available data on lethal loci largely stemIn Yeast, Worms, Flies, and Mice, Only About1 in 3 Genes Is Essential for Viability from three sources: from the 263 gene knockouts summarized by Brandon et al. (1995)。 from small promoterThe consequences of some genomic perturbations cannot be pensated for by normal epigeic processes trap analyses, such as that of Friedrich and Soriano(1991)。 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。 Lewin, 1994), but new data allow us to refine this figure to the whole genome is not known. In the promoter trapstudy, 9 out of 24 knockout strains yield homozygousdownward. We have evaluated the published data from27 different chromosomal regions that have been sub embryonic lethals, indicating that there would be approximately 26,000 lethal loci if these figures were to extensive mutagenesis. From this large sampleprising a quarter of the fly genome, we estimate that In the geic analysis of the t region, 17 lethal loci wererecovered, and it is on this minute sample that the figurethere are approximately 3,600 lethal loci in a Drosophilagenome of 12,000 genes (Table 2). of 5,000 to 10,000 lethal loci in the mouse genome isCell524Table 3. Estimation of Lethal Loci in Different Regions of the C. elegans GenomeChromosome Length in Loci Predicted Extrapolated NumberRegion Map Units Found Number of Loci per Genomeunc22(sDf2)Chromosome 4 31 48 3500hDf6Chromosome I 19 25 3300eT1(III。 IV)Chromosome 5 101 120 2850based (Dove 1987). It is clear that an estimate of the On a CD1 background, the mutant mice live for 3 weeksor so (Threadgill et al., 1995). Similarly, the mouse acnumber of lethal loci in the mouse genome is uncertain,and presently ranges from 5,000 to 26,000. tivin/inhibin bB subunit knockout has an eye defect thatis not seen in a 129/Sv background, but is perant inboth 129/Sv 3 C57BL/6 and 129/Sv 3 BALB/c backThe Phenotypic Consequences of Gene InactivationDepend on Geic Background grounds (Vassalli et al., 1994). Different geic backgrounds can allow or eliminate intestinal tumors in mice,The interpretation of gene inactivation, deletion, orknockout data needs to be treated with caution (Erick and in humans there is variation among different members of the same family inheriting the APC mutation,son, 1993。 Weintraub, 1993。 Thomas, 1993。 Crossin,1994。 Pickett and MeeksWagner, 1995), since detecting which predisposes them to colon cancer (Dietrich et al.,1993). The human phenotypic spectrum can differ fromsubtle phenotypic alterations under laboratory conditions is difficult. In addition, the current methods used that of the mouse for the same gene, the perturbationsof the ret receptor tyrosine kinase being a good examplein evaluating function are often inadequate, and smallreductions in。