NEWS AND VIEWS 1A deletion, although paternal inheritance of the deletion allows rescue of maternal inheri- tance of Gnas deficiency. In humans, there is again LOI (gain of silencing) and acquisition of DNA methylation, leading to PHP Ib when on the maternal chromosome, which should have higher expression. The human equiva- lent of paternal deficiency of XLαs 1 has yet to be described. There are rare human parallels to the mouse paternal and maternal uni- parental disomy (UPD; MatDp(dist2) and PatDp(dist2) in Plagge et al. 2 ). Maternal UPD 20 is associated with growth retarda- tion 5 in several cases; a single report of mosaic paternal UPD 20 showed multiple birth defects, but the relevance of the UPD to the phenotype was not clear 6 , and other cases would be instructive. Two individuals with constitutional deletions of chromosomes 20q were found to have Albright hereditary osteodystrophy; an individual with a paternal deletion had PPHP and an individual with a maternal deletion had PHP Ia 7 . The many uses of imprinting Plagge et al. 2 conclude that their data provide “tangible molecular support for the parental conflict hypothesis of imprinting.” In this hypothesis, genomic imprinting allows the paternal genome to promote growth of the fetus and the maternal genome to inhibit growth, with the interpretation that smaller offspring give advantage to the maternal genome and larger offspring give advantage to the paternal genome. There are many other hypotheses for the evolutionary advan- tages provided by genomic imprinting. We championed a ‘rheostat’ model based on the advantages of improved and reversible evolv- ability for certain genes associated with a continuous rather than discontinuous geno- type-phenotype relationship 8 . This might be particularly true if fitness of the phenotypic spectrum varied with environmental condi- tions. In this context, increased heterogeneity among individuals for the abundance of such gene products might be advantageous, par- ticularly in the context of advantages to the group. Genes with threshold effects, such as haploinsufficiency for transcription factors, often lead to deleterious malformation phe- notypes, and increased heterogeneity among individuals for the abundance of such gene products would probably be deleterious, with no advantage for imprinting. The evolution- ary selection for imprinted genes involves both genetic and epigenetic variation. In the conflict hypothesis, the genotype and epigenotype under selection relate to the individual parent and offspring, in contrast to the selection for the hypervariable popula- tion under the rheostat model. The conflict hypothesis and the rheostat hypothesis are not mutually exclusive. It is easy to imagine how the rheostat hypothesis might apply to a broad range of imprinted phenotypes, whereas the conflict hypothesis might be most relevant to imprinted control of growth. The data of Plagge et al. 2 might be equally interpreted to be compatible with a continuous genotype-phenotype relation- ship and for a rheostat model. In the case of Gnas, increased 'evolvability' of body size could be advantageous in itself, but it is also advantageous for the paternal genome to promote growth and the maternal genomes to promote the opposite. 1. Williamson, C.M. et al. Nat. Genet. 36, 894–899 (2004). 2. Plagge, A. et al. Nat. Genet. 36, 818–826 (2004). 3. Jiang, Y., Bressler, J. & Beaudet, A.L. Ann. Rev. Genomics Hum. Genet. (in the press). 4. Spiegel, A.M. & Weinstein, L.S. Ann. Rev. Med. 55, 27–39 (2004). 5. Eggermann, T. et al. J. Med. Genet. 38, 86–89 (2001). 6. Venditti, C.P., Hunt, P., Donnenfeld, A., Zackai, E. & Spinner, N.B. Am. J. Med. Genet. 124A, 274–279 (2004). 7. Aldred, M.A. et al. Am. J. Med. Genet 113, 167–172 (2002). 8. Beaudet, A.L. & Jiang Y. Am. J. Hum. Genet. 70, 1389–1397 (2002). NATURE GENETICS VOLUME 36 | NUMBER 8 | AUGUST 2004 795 STARTing to recycle Gavin Sherlock A comprehensive microarray-based analysis of the cell cycle shows that periodic transcription of most genes is not conserved between Schizosaccharomyces pombe and Saccharomyces cerevisiae. A core group of ∼40–80 genes have conserved patterns of transcription and may have key roles in cell cycle progression. Proper regulation of the cell cycle is crucial to the growth and development of all organ- isms; understanding this regulation is central to the study of many diseases, most notably cancer. Since the discovery that cdc2 mutants in S. pombe can be complemented by the orthologous gene CDC28 from S. cerevisiae 1 and the gene CDC2 from human 2 , it has been known that essential components of the eukaryotic cell cycle machinery are con- served from yeast to humans. Numerous examples of orthologous cell cycle proteins in all eukaryotes have since been found (e.g., the MCM proteins 3 ). The genome-wide tran- scriptional program during the cell cycle has been investigated in a wide range of organ- isms, including budding yeast 4,5 , bacteria 6 , primary human fibroblasts 7,8 , mouse fibrob- lasts 9 and HeLa cells 10,11 . But a comprehen- sive analysis of the level of conservation of periodic expression of genes involved in the cell cycle has been lacking. On page 809 of this issue, Gabriella Rustici and colleagues 12 present a comprehensive characterization of transcription during the S. pombe cell cycle and show, by comparison with S. cerevisiae data, that relatively few genes have conserved transcriptional regulation during the cell cycle (Fig. 1). Conserved expression Rustici et al. 12 identified 407 periodically tran- scribed genes using eight time-course experi- ments and several different synchronization procedures. The ‘phaseogram’ in Figure 1 of their paper shows periodic expression, which is reproduced with similar kinetics and phases of peak transcription across all of their experi- ments. Of these 407 genes, 136 have ‘high- amplitude’ changes and cluster in four waves of expression. Among these 136 high-ampli- tude genes, 87 have clear orthologs in S. cere- visiae and about 40 of these are periodically expressed in both yeasts. In and of itself, 40 of these 87 genes being periodically expressed in both organisms is highly significant (P = 4.3 × 10 –32 ), because choosing 87 S. pombe genes at Gavin Sherlock is at the Department of Genetics, Stanford University Medical School, Stanford, Ca, USA. e-mail: sherlock@genome.stanford.edu © 2004 Nature Publishing Group http://www.nature.com/naturegenetics