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To determine which changes are beneficial us who we are. The authors’ work provides an 3. Urnov, F. D., Rebar, E. J., Holmes, M. C., Zhang, H. S. to the cell and which detrimental, Findlay excellent case in point to support the words & Gregory, P. D. Nature Rev. Genet. 11, 636–646 11 (2010). and colleagues used deep sequencing, which of geneticist Sydney Brenner : “Progress 4. Joung, J. K. & Sander, J. D. Nature Rev. Mol. Cell Biol. reads every copy of every gene in every cell in science results from new technologies, 14, 49–55 (2013). 5. Ran, F. A. et al. Nature Protocols 8, 2281–2308 of a population. Immediately after editing, new discoveries and new ideas, probably in (2013). the cells are a kaleidoscope of genetic diver- that order.” ■ 6. Urnov, F. D. et al. Nature 435, 646–651 (2005). sity. Edited cells account for only 1–3% of the 7. Goldberg, A. D. et al. Cell 140, 678–691 (2010). total cell population (lower than seen in other Fyodor D. Urnov is at Sangamo BioSciences 8. Doyon, J. B. et al. Nature Cell Biol. 13, 331–337 2 (2011). studies ), but this is not a real problem because Inc., Richmond, California 94804, USA. 9. Sexton, A. et al. Genes Dev. http://dx.doi. deep sequencing can identify even very rare e-mail: [email protected] org/10.1101/gad.246819.114 (2014). DNA sequences. 10. Braberg, H. et al. Cell 154, 775–788 (2013). 1. Findlay, G. M., Boyle, E. A., Hause, R. J., Klein, J. C. & 11. Robertson, M. Nature 285, 358–359 (1980). After a few days, a stark change occurs. Shendure, J. Nature 513, 120–123 (2014). Many new sequences disappear or dimin- 2. Carroll, D. Annu. Rev. Biochem. 83, 409–439 (2014). This article was published online on 20 August 2014. ish in number. This is survival of the fittest at the cellular level. The authors found that cells unlucky enough to acquire a change in COSMOLOGY a nucleo­tide needed for gene function died immediately, but cells that had more-benign errors lived on. This experiment provides a remarkable functional map of this bit of Meet the Laniakea genetic text — we know whether each and every position makes a useful contribution to the working of the whole protein. supercluster Some genetic changes do not affect what a protein does, but rather how messenger RNA An analysis of a three-dimensional map of galaxies and their velocities reveals molecules are put together such that sections the hitherto unknown edges of the large system of galaxies in which we that do not specify the sequence of a protein live — dubbed the Laniakea supercluster. See Letter p.71 are removed (a process known as splicing). Findlay and co-workers investigated how DNA sequence affects splicing in BRCA1, mutations ELMO TEMPEL catalogue of galaxies that has allowed them to in which cause breast cancer, in some cases do just that. because of improper splicing. ne of the greatest advances in cosmol- The large-scale structure of the Universe is The authors generated almost every possible ogy has been the discovery of how an intricate network of clusters, filaments and sequence in a 6-base-pair stretch of BRCA1, matter and light are organized on superclusters of galaxies, together with cosmic and investigated which sequences helped the Oscales larger than those of galaxies1,2. How- voids that are almost empty of galaxies. Super­ gene to be copied into normal RNA, and which ever, despite tremendous effort, astronomers clusters are extended regions containing a large prevented it. They took this remarkable group have been unable to map in detail the large- number of galaxies, but this concept is rather of 4,048 different kinds of cell, growing side by scale cosmic structure in which the Milky Way vague; researchers lack a robust, quantitative side in the same Petri dish, and measured how resides. Now, on page 71 of this issue, Tully definition for them. Tully and colleagues have often each sequence occurred in BRCA1 DNA et al.3 report an analysis of data from a vast found a neat way of identifying the edges of and the corresponding RNA. Some sequences were never found in RNA, giving an insight into which genetic signals control how RNA 3 REF. acquires its fully functional form. Findlay and colleagues have provided a way to find meaning in the text of human DNA, by systematically analysing each nucleotide in a gene in its normal setting in the chromosome. All you need is a robust way to edit your region of interest3–5 and a method to assay the cellular consequences of editing. The word ‘random’ Laniakea often has negative connotations in science, but not in this instance. Making random changes Perseus–Pisces in a gene and letting nature take its course is enormously informative. For instance, a major Shapley challenge for women who carry a mutation in BRCA1 is to determine the risk of contract- ing cancer for their specific mutation. Find- lay and co-workers’ approach can be used to address this problem and to determine which specific BRCA1 mutations are the most worrisome. Figure 1 | The edges of our home supercluster of galaxies. The image shows a slice through the More generally, the juxtaposition of genome Laniakea supercluster and adjacent Shapley and Perseus–Pisces superclusters, as identified by Tully and editing and deep-sequencing technologies will, colleagues3. Areas of high galaxy density are shown in red and cosmic voids in dark blue. The Milky Way without doubt, provide a basis for progress in galaxy lies essentially in a plane parallel to the slice in the centre of the figure. Velocity streams along our quest to understand how our DNA makes which galaxies move within our supercluster are shown in white, with other velocity streams in dark blue.

4 SEPTEMBER 2014 | VOL 513 | NATURE | 41 © 2014 Macmillan Publishers Limited. All rights reserved RESEARCH NEWS & VIEWS superclusters by examining the motions of by the places at which the velocity flow field fully understand what processes affected the galaxies. In doing so, they have detected the points in different directions on either side of formation of cosmic structures in our local boundaries of our home supercluster, which the boundary. This is the first clear definition Universe. This is a challenging task, but one they have called the Laniakea supercluster. of a supercluster. The downside of it is that it that is worthwhile and that we must hope will Their paper is supplemented by a beautiful requires dynamical information that is avail- be tackled using future surveys. movie (http://irfu.cea.fr/laniakea) that shows able only for the nearby Universe. Finally, I praise the choice of the name our supercluster and its dynamical connection Tully et al. find several basins of attraction in Lania­kea for Earth’s supercluster. It is taken to other neighbouring large-scale systems. our corner of the Universe, including Lania­kea from the Hawaiian words lani, which means The movie is essential for comprehending the and the previously known Perseus–Pisces and heaven, and akea, which means spacious complexity of cosmic structures. Shapley superclusters. Laniakea has a diameter or immeasurable. That is just the name one Mapping the large-scale structure of the of 160 million parsecs (520 million light years), would expect for the whopping system that nearby region of the Universe is important for and is much bigger than already identified we live in. ■ several reasons. First, it reveals details of the superclusters in our local neighbourhood. large-scale cosmic structures that surround the However, it is smaller than the largest super- Elmo Tempel is in the Department of Milky Way. These details are nearly impossi- clusters that have been found in the more dis- Cosmology, Tartu Observatory, Tõravere ble to observe for systems far away from Earth. tant Universe8. It is a surprise that Laniakea was 61602, Estonia. Second, the morphology of the nearby Uni- not spotted in previous astronomical surveys. It e-mail: [email protected] verse is essential for a precise determination seems that measurements of the peculiar velo­ 1. Jõeveer, M., Einasto, J. & Tago, E. Mon. Not. R. Astron. of cosmological parameters such as the density cities of galaxies are essential for identifying the Soc. 185, 357–370 (1978). of dark energy4, which is thought to drive the boundaries of some superclusters. 2. Bond, J. R., Kofman, L. & Pogosyan, D. Nature 380, acceleration of the expanding Universe. Third, Of course, these results do not mark the 603–606 (1996). 3. Tully, R. B., Courtois, H., Hoffman, Y. & Pomarède, D. examination of cosmic structures around the end of mapping the Universe. Although Tully Nature 513, 71–73 (2014). Milky Way will help us to understand how et al. used the best galaxy catalogue available, 4. Sinclair, B., Davis, T. M. & Haugbølle, T. Astrophys. J. the Galaxy formed and evolved5, and galaxy- these data do not extend far enough in cosmic 718, 1445–1455 (2010). 5. Shaya, E. J. & Tully, R. B. Mon. Not. R. Astron. Soc. formation processes in general. space to explain the motion of our Galaxy with 436, 2096–2119 (2013). Tully and colleagues’ study is based on data respect to the rest frame of the cosmic micro- 6. Tully, R. B. et al. Astron. J. 146, 86 (2013). from the Cosmicflows-2 galaxy catalogue6. wave background — relic radiation from the 7. Zaroubi, S., Hoffman, Y. & Dekel, A. Astrophys. J. 520, 413–425 (1999). The authors combined existing measure- Big Bang. The Universe must be mapped on a 8. Liivamägi, L. J., Tempel, E. & Saar, E. Astron. ments of the velocities at which galaxies recede much bigger scale than that achieved here to Astrophys. 539, A80 (2012). from Earth — which are mainly caused by the cosmic expansion and provide an indirect estimate of how far away they are — with STRUCTURAL BIOLOGY direct galaxy distance measurements from the Cosmicflows-2 data set. This enabled them to derive the ‘peculiar velocities’ of the galaxies, that is, their true velocity relative to How fluorescent RNA a rest frame. The peculiar velocity is obtained by subtracting the contribution of the cosmic expansion, which is determined using the gets its glow direct distance measurement, from the reces- sion velocity. Fluorescent tags are proving invaluable for tracking RNA molecules in cells. Two Direct distance measurements of galaxies sets of crystal structures for one such tag — an RNA motif that fluoresces when are extremely difficult to perform, and the lack bound to a dye — will aid the development of even better markers. of such data has limited this kind of analysis in the past. However, the use of peculiar velocities can provide information about cosmic struc- WILLIAM G. SCOTT individual RNA molecules in cells. tures that is otherwise hard to obtain. And in Fluorescence occurs when light shone on a the present case, it allowed the extent, structure reen fluorescent protein is widely molecule is absorbed, exciting the molecule, and dynamics of Earth’s supercluster, as well used as a visualization marker for and is then re-emitted. The energy of the emit- as those of other nearby superclusters, to be biological molecules, and has revo- ted light is lower than that absorbed, so a mol- determined. We can only imagine what other Glutionized microscopic imaging in biological ecule excited by invisible ultraviolet light, for details and structures might be uncovered if systems — a fact celebrated by the award of example, may fluoresce as highly visible green additional direct-distance measurements of the 2008 Nobel Prize in Chemistry1. Engi- light. Because the fluorescent light is emitted galaxies are carried out. neered fluorescent RNAs are potentially in every direction, it can be measured at 90° A noteworthy aspect of Tully and colleagues’ equally useful, and a green fluorescent RNA from the direction of the light used to excite study is the use of Wiener filtering7 — a nifty motif 2 called Spinach has been developed for the molecule. Taken together, these effects algorithm that translates an incomplete map of this purpose. Uncovering the structural basis can produce a highly sensitive signal with peculiar velocities of galaxies into a complete for how fluorescent RNAs work is crucial to little background noise, potentially allow- map of the underlying distribution (density realizing their full potential as experimental ing the detection of just one or a very few field) and dynamics (velocity flow field) of tools. Two sets of crystal structures of Spinach molecules in a cell. matter (Fig. 1). It is this technique that allowed — one reported by Huang et al.3 in Nature Proteins are not normally fluorescent. the authors to come up with a quantitative Chemical Biology, and the other by Warner Green fluorescent protein (GFP), however, is definition of a supercluster. According to their et al.4 in Nature Structural and Molecular Biol- an unusual enzyme that catalyses the chemical definition, a supercluster is a ‘basin of attrac- ogy — now provide a deeper understanding rearrangement of some of its own amino-acid tion’ in the velocity flow field. In other words, of how it fluoresces, and should enable the side chains, creating an embedded molecule the boundaries of a supercluster are defined design of improved labels for visualizing — known as a fluorophore — that absorbs

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