The DNA sequence of human chromosome 22

Knowledge of the complete genomic DNA sequence of an organism allows a systematic approach to defining its genetic components. The genomic sequence provides access to the complete structures of all genes, including those without known function, their control elements, and, by inference, the proteins they encode, as well as all other biologically important sequences. Furthermore, the sequence is a rich and permanent source of information for the design of further biological studies of the organism and for the study of evolution through cross-species sequence comparison. The power of this approach has been amply demonstrated by the determination of the sequences of a number of microbial and model organisms. The next step is to obtain the complete sequence of the entire human genome. Here we report the sequence of the euchromatic part of human chromosome 22. The sequence obtained consists of 12 contiguous segments spanning 33.4 megabases, contains at least 545 genes and 134 pseudogenes, and provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome.     

High-quality male field crickets invest heavily in sexual display but die young

Only high-quality males can bear the costs of an extreme sexual display. As a consequence, such males are not only more attractive, but they often live longer than average. Recent theory predicts, however, that high-quality males should sometimes invest so heavily in sexual displays that they die sooner than lower quality males. We manipulated the phenotypic quality of field crickets, Teleogryllus commodus, by altering the protein content of their diet. Here we show that nymphs and adult females reared on a high-protein diet lived longer than those on a low-protein diet. In contrast, adult males reared on a high-protein diet died sooner than those on low-protein diets because they invested more energy in calling during early adulthood. Our findings uphold the theoretical prediction that the relationship between longevity and sexual advertisement may be dynamic (that is, either positive or negative), depending on local conditions such as resource availability. Moreover, they caution the use of longevity as a proxy for fitness in sexual selection studies, and suggest avenues for future research on the relationship between sexual attractiveness and ageing.     

CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair

Inherited mutations in BRCA2 are associated with a predisposition to early-onset breast cancers. The underlying basis of tumorigenesis is thought to be linked to defects in DNA double-strand break repair by homologous recombination. Here we show that the carboxy-terminal region of BRCA2, which interacts directly with the essential recombination protein RAD51, contains a site (serine 3291; S3291) that is phosphorylated by cyclin-dependent kinases. Phosphorylation of S3291 is low in S phase when recombination is active, but increases as cells progress towards mitosis. This modification blocks C-terminal interactions between BRCA2 and RAD51. However, DNA damage overcomes cell cycle regulation by decreasing S3291 phosphorylation and stimulating interactions with RAD51. These results indicate that S3291 phosphorylation might provide a molecular switch to regulate RAD51 recombination activity, providing new insight into why BRCA2 C-terminal deletions lead to radiation sensitivity and cancer predisposition.     

The DNA sequence of the human X chromosome

The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.     

An SNP map of human chromosome 22

The human genome sequence will provide a reference for measuring DNA sequence variation in human populations. Sequence variants are responsible for the genetic component of individuality, including complex characteristics such as disease susceptibility and drug response. Most sequence variants are single nucleotide polymorphisms (SNPs), where two alternate bases occur at one position. Comparison of any two genomes reveals around 1 SNP per kilobase. A sufficiently dense map of SNPs would allow the detection of sequence variants responsible for particular characteristics on the basis that they are associated with a specific SNP allele. Here we have evaluated large-scale sequencing approaches to obtaining SNPs, and have constructed a map of 2,730 SNPs on human chromosome 22. Most of the SNPs are within 25 kilobases of a transcribed exon, and are valuable for association studies. We have scaled up the process, detecting over 65,000 SNPs in the genome as part of The SNP Consortium programme, which is on target to build a map of 1 SNP every 5 kilobases that is integrated with the human genome sequence and that is freely available in the public domain.     

One-dimensional nature of the magnetic fluctuations in YBa2Cu3O6.6

There is increasing evidence that inhomogeneous distributions of charge and spin--so-called 'striped phases'--play an important role in determining the properties of the high-temperature superconductors. For example, recent neutron-scattering measurements on the YBa2Cu3O(7-x) family of materials show both spin and charge fluctuations that are consistent with the striped-phase picture. But the fluctuations associated with a striped phase are expected to be one-dimensional, whereas the magnetic fluctuations observed to date appear to display two-dimensional symmetry. We show here that this apparent two-dimensionality results from measurements on twinned crystals, and that similar measurements on substantially detwinned crystals of YBa2Cu3O6.6 reveal the one-dimensional character of the magnetic fluctuations, thus greatly strengthening the striped-phase interpretation. Moreover, our results also suggest that superconductivity originates in charge stripes that extend along the b crystal axis, where the superfluid density is found to be substantially larger than for the a direction.     

Rauwolfia alkaloids,XVI. Deserpidine,a new alkaloid fromRauwolfia canescens

Zusammenfassung AusRauwolfia canescens wurde Deserpidin, C₃₂H₃₈O₈N₂, isoliert und eine Konstitutionsformel für dieses neue Alkaloid vorgeschlagen.

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Communication XV,C. F. Huebner et al., J.A.C.S. (in press).

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From lecture given at Columbia University, New York, January 12th, 1955.