Hot off the presses! Jul 01 Nat Rev Genet

The Jul 01 issue of the Nat Rev Genet is now up on Pubget (About Nat Rev Genet): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• From the editors
  - Nat Rev Genet 10(7):423 (2009)
  
• Genome evolution: Hit repeat for evolvability
  - Nat Rev Genet 10(7):424 (2009)
  
• RNA world: A new class of small RNAs
  - Nat Rev Genet 10(7):425 (2009)
  
• In brief: Mobile elements, Epigenetics, Genome instability, Technology
  - Nat Rev Genet 10(7):425 (2009)
  
• Small RNAs: Microbial metatranscriptomics goes deep
  - Nat Rev Genet 10(7):426 (2009)
  
• Genome evolution: A manual way to the ancestral genome
  - Nat Rev Genet 10(7):426 (2009)
  
• Transcriptomics: Revealing the extent of RNA editing
  - Nat Rev Genet 10(7):426 (2009)
  
• In brief: Human disease, Gene regulation, Animal models, Plant genetics
  - Nat Rev Genet 10(7):427 (2009)
  
• RNA processing: Viral infection has a sting in the tail
  - Nat Rev Genet 10(7):428 (2009)
  
• Human disease: Malaria GWA study brings progress for infectious disease genetics
  - Nat Rev Genet 10(7):428 (2009)
  
• Development: Cells size themselves up
  - Nat Rev Genet 10(7):429 (2009)
  
• An Interview With... Louis Kunkel
  - Nat Rev Genet 10(7):430 (2009)
  
• The genetic contribution to non-syndromic human obesity
  - Nat Rev Genet 10(7):431-442 (2009)
  The last few years have seen major advances in common non-syndromic obesity research, much of it the result of genetic studies. This Review outlines the competing hypotheses about the mechanisms underlying the genetic and physiological basis of obesity, and then examines the recent explosion of genetic association studies that have yielded insights into obesity, both at the candidate gene level and the genome-wide level. With obesity genetics now entering the post-genome-wide association scan era, the obvious question is how to improve the results obtained so far using single nucleotide polymorphism markers and how to move successfully into the other areas of genomic variation that may be associated with common obesity.
• From DNA sequence to transcriptional behaviour: a quantitative approach
  - Nat Rev Genet 10(7):443-456 (2009)
  Complex transcriptional behaviours are encoded in the DNA sequences of gene regulatory regions. Advances in our understanding of these behaviours have been recently gained through quantitative models that describe how molecules such as transcription factors and nucleosomes interact with genomic sequences. An emerging view is that every regulatory sequence is associated with a unique binding affinity landscape for each molecule and, consequently, with a unique set of molecule-binding configurations and transcriptional outputs. We present a quantitative framework based on existing methods that unifies these ideas. This framework explains many experimental observations regarding the binding patterns of factors and nucleosomes and the dynamics of transcriptional activation. It can also be used to model more complex phenomena such as transcriptional noise and the evolution of transcriptional regulation.
• Transcription factories: gene expression in unions?
  - Nat Rev Genet 10(7):457-466 (2009)
  Transcription is a fundamental step in gene expression, yet it remains poorly understood at a cellular level. Visualization of transcription sites and active genes has led to the suggestion that transcription occurs at discrete sites in the nucleus, termed transcription factories, where multiple active RNA polymerases are concentrated and anchored to a nuclear substructure. However, this concept is not universally accepted. This Review discusses the experimental evidence in support of the transcription factory model and the evidence that argues against such a spatially structured view of transcription. The transcription factory model has implications for the regulation of transcription initiation and elongation, for the organization of genes in the genome, for the co-regulation of genes and for genome instability.
• Making a firm decision: multifaceted regulation of cell fate in the early mouse embryo
  - Nat Rev Genet 10(7):467-477 (2009)
  The preimplantation mammalian embryo offers a striking opportunity to address the question of how and why apparently identical cells take on separate fates. Two cell fate decisions are taken before the embryo implants; these decisions set apart a group of pluripotent cells, progenitors for the future body, from the distinct extraembryonic lineages of trophectoderm and primitive endoderm. New molecular, cellular and developmental insights reveal the interplay of transcriptional regulation, epigenetic modifications, cell position and cell polarity in these two fate decisions in the mouse. We discuss how mechanisms proposed in previously distinct models might work in concert to progressively reinforce cell fate decisions through feedback loops.
• Understanding what determines the frequency and pattern of human germline mutations
  - Nat Rev Genet 10(7):478-488 (2009)
  Surprising findings about human germline mutation have come from applying new technologies to detect rare mutations in germline DNA, from analysing DNA sequence divergence between humans and closely related species, and from investigating human polymorphic variation. In this Review we discuss how these approaches affect our current understanding of the roles of sex, age, mutation hot spots, germline selection and genomic factors in determining human nucleotide substitution mutation patterns and frequencies. To enhance our understanding of mutation and disease, more extensive molecular data on the human germ line with regard to mutation origin, DNA repair, epigenetic status and the effect of newly arisen mutations on gamete development are needed.
• Challenges of translating genetic tests into clinical and public health practice
  - Nat Rev Genet 10(7):489-495 (2009)
  Research in genetics and genomics has led to an expanding list of molecular genetic tests, which are increasingly entering health care systems. However, the evidence surrounding the benefits and harms of these tests is frequently weak. Here we present the main challenges to the successful translation of new research findings about genotype–phenotype associations into clinical practice. We discuss the means to achieve an accelerated translation research agenda that is conducted in a reasonable, fair and efficient manner.
• Mitochondrial and plastid evolution in eukaryotes: an outsiders' perspective
  - Nat Rev Genet 10(7):495-505 (2009)
  The eukaryotic organelles mitochondrion and plastid originated from eubacterial endosymbionts. Here we propose that, in both cases, prokaryote-to-organelle conversion was driven by the internalization of host-encoded factors progressing from the outer membrane of the endosymbionts towards the intermembrane space, inner membrane and finally the organelle interior. This was made possible by an outside-to-inside establishment in the endosymbionts of host-controlled protein-sorting components, which enabled the gradual integration of organelle functions into the nuclear genome. Such a convergent trajectory for mitochondrion and plastid establishment suggests a novel paradigm for organelle evolution that affects theories of eukaryogenesis.