Something to swing about The first gibbon genome to be sequenced provides clues about how genomes can be shuffled in short evolutionary time frames, and about how gibbons adapted and diversified in the jungles of southeast Asia. See Article p.195 MICHAEL J. O’NEILL & RACHEL J. O’NEILL


he gibbon — a singing, swinging, southeast-Asian ape of the Hylobatidae family — occupies a poorly understood branch of the primate family tree. Despite being superficially similar to monkeys, gibbons share many traits with humans: pair bonding and monogamy; the lack of a tail; the ability to walk upright on legs; and a fondness for singing. Our understanding of gibbon evolution is now set to improve because they have just joined an exclusive primate club whose members include humans, chimpanzees and orangutans. On page 195 of this issue, Carbone et al.1 report that they have sequenced the genome of Asia, a white-cheeked gibbon of the Nomascus genus. Their analysis unveils unique genomic features that shed light on some of the mysteries surrounding the evolutionary history of this remarkable mammalian family. The genomes of almost all eukaryotes (plants, fungi and animals) are organized into blocks of DNA that undergo periodic reorganization. These reshuffling events, which typically occur in small increments, can lead to the emergence of species with distinct variations in karyotype — an organism’s chromosome structure and number. How reshuffling occurs, and what factors lead to the fixation of new karyotypes, is an abiding genetic mystery,

Human Chimpanzee Gorilla


Millions of years ago

but mobile DNA elements are thought to have a role in some genome rearrangements. These DNA sequences, which were discovered more than 50 years ago2, can move from one location in the genome to another, often leaving a copy of themselves behind. By comparing Asia’s genome with those of three other gibbons of the genera Hylobates, Hoolock and Symphalangus, Carbone and colleagues dated the divergence of gibbons from the great apes at roughly 17 million years ago (Fig. 1). However, they found that in a strikingly rapid series of speciation events that spanned 2 million years or less, an ancestral gibbon quickly gave rise to the four genera of extant gibbons. Coinciding with and perhaps reinforcing this rapid speciation is an unusually fluid karyotype3 — the chromosomes of different gibbon species are more structurally diverse than those of any of the great apes. Carbone and co-workers suggest that the gibbon’s extreme chromosomal diversity may be attributable to a family of mobile DNA elements that is not found in other primate lineages. These LINE-1-Alu-VNTR-Alu-like (LAVA) elements are named after the three distinct mobile elements from which they derive4. Although each of the parental elements is common to all apes, the composite is unique to the gibbon lineage, with its origin dating to the time gibbons split from the great-ape lineage.

Gibbon Orangutan



Green monkey


Figure 1 | Evolution of gibbons.  A phylogenetic tree illustrates the evolution of great-ape species in relation to monkeys (indicated by the green monkey). Carbone et al.1 estimate that gibbons separated from the great apes around 17 million years ago. The scale for divergence times is indicated on the left. The phylogeny is superimposed on a map to show where each lineage arose (although not the green monkey). 1 7 4 | NAT U R E | VO L 5 1 3 | 1 1 S E P T E M B E R 2 0 1 4

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The authors’ examination of the four genomes revealed the profound impact of LAVA elements on gibbon genome dynamics. In several places, insertion of LAVA elements caused premature termination of gene transcription, which might lead to the production of proteins with altered functions. The affected genes notably include several that are involved in chromosome segregation, whereby replicated chromosomes are equally distributed to progeny during cell division. Carbone et al. propose a scenario in which LAVA insertion results in subtly altered proteins that mildly disrupt chromosome segregation and so enhance genome plasticity. However, major alterations or a loss of function of these genes would lead to sterility or death, limiting the ability of LAVA elements to generate new chromosome arrangements. Lending credence to the subtle-alteration model, Carbone and colleagues found that the gibbon genome contained 240 short segments (most around 150 base pairs in length) in which mutations resulting in basepair substitutions have occurred faster than expected since separation from the great-ape lineage — a hallmark of adaptive evolution. These regions mostly lie close to the genes affected by LAVA insertions. The authors speculate that the regions may have diversified specifically in gibbons to ameliorate the detrimental effects of active LAVA elements; functional elements that modulate the impact of LAVA insertions on gene transcription were created, such as enhancers (which control gene expression from a distance)4. Such gene disruptions, coupled with population-size fluctuations across southeast Asia during the Miocene-to-Pliocene transition 2.5 million years ago, may have led to the extraordinary chromosomal diversity displayed in extant gibbons. Several other eukaryotic groups underwent rapid diversification in karyotype as they evolved5, including sunflowers, Australian grasshoppers, horses and kangaroos, and the emergence of some of these species coincided with notable activity of mobile DNA. However, proof of Carbone and colleagues’ subtle-alteration model will require thorough and integrative functional and evolutionary genomic analyses — a strategy that has been of great benefit to


can be linked to specific changes at the genome level in primates. Further exploration of the gibbon genome may shed light on other features we share with gibbons, such as their ability to sing like human operatic sopranos8 and their penchant for walking on two legs. Publication of Asia’s genome gives us something to sing about — and to swing about. Michael J. O’Neill and Rachel J. O’Neill are at the Institute for Systems Genomics and Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut 06269, USA. e-mails: [email protected]; [email protected] Figure 2 | King of the swingers.  A gibbon brachiating through the trees.

other large-scale genomics efforts6. Gibbons almost fly through the trees, hitting speeds of up to 56 kilometres an hour using only their arms in a pendulum motion termed brachiation7 (Fig. 2). The physiological features that allow this fluid and swift motion include long and powerful arms, permanently hooked hands, and a ball-and-socket wrist joint that enables swift changes in direction,

even at high velocities. The authors found evidence that genes important to forelimb patterning and specialization in the gibbon have experienced a rapid evolution not seen in other primate lineages. Establishing a functional link between the adaptive evolution of these genes and gibbon brachiation is an exciting future direction — it could provide the first evidence that anatomical and locomotive specialization


Bacteria get vaccinated Infection by defective bacterial viruses that cannot replicate has now been found to be the key feature enabling bacteria to rapidly develop adaptive immunity against functional viruses. RODOLPHE BARRANGOU & TODD R. KLAENHAMMER


urviving viral infections is a necessary ability for most life forms. Adaptive immunity, in which invasive elements are captured by the cell, allowing subsequent recognition and destruction of related viruses, is crucial for overcoming such infections. As such, adaptive immunity drives evolution, selection and fitness. Although the antibody–antigen basis of mammalian adaptive immunity has been extensively characterized, its counterpart in archaea and bacteria — CRISPR–Cas immune systems — remains largely mysterious. Writing in Nature Communications, Hynes et al.1 describe how defective virus particles trigger immunization events by CRISPR–Cas systems, conferring adaptive immunity in the bacteria against related functional viruses. CRISPR–Cas systems have two components: DNA sequences comprised of clustered

regularly interspaced short palindromic repeats (CRISPR), and CRISPR-associated sequence (Cas) endonuclease enzymes. Typically, immunity arises when invasive genetic elements (for example, DNA injected into the cell by bacterial viruses called bacteriophages, or phages) are incorporated into the genome as ‘spacers’ between CRISPR sequences2. Subsequent transcription of the CRISPR array containing the incorporated spacers leads to the production of small interfering CRISPR RNAs3, which guide Cas enzymes to target and cleave DNA sequences that are complementary to the spacers4–6. This adaptive immune system has proven to be effective against phage predation in dairy starter cultures, which are widely used in yogurt and cheese manufacturing2. Although it has been established that the uptake of viral DNA into the host genome drives CRISPR-based immunity5, little is known about how bacteria sample the genomes of phages for spacer acquisition, or the dynamics of the immunization process, which

1. Carbone, L. et al. Nature 513, 195–201 (2014). 2. McClintock, B. Genetics 38, 579–599 (1953). 3. Müller, S., Hollatz, M. & Wienberg, J. Hum. Genet. 113, 493–501 (2003). 4. Carbone, L. et al. Genome Biol. Evol. 4, 648–658 (2012). 5. King, M. Chromosomal Speciation Revisited (Again). Species Evolution. The Role of Chromosome Change (Cambridge Univ. Press, 1993). 6. The ENCODE Project Consortium. PLoS Biol. 9, e1001046 (2011). 7. Michilsens, F., Vereecke, E. E., D’Août, K. & Aerts, P. J. Anat. 215, 335–354 (2009). 8. Koda, H. et al. Am. J. Phys. Anthropol. 149, 347–355 (2012).

can be thought of as a bacterial ‘vaccination’ against phages. Phages typically take over the molecular machinery of their host within minutes, and the ability of bacteria to mount a quick adaptive immune response has remained enigmatic. Hynes et al. first exposed bacterial cells to defective phages. These were produced either by exposing phages to ultraviolet (UV) radiation or by using virulent phages that are susceptible to a restriction–modification (RM) system that uses restriction enzymes to cleave phage DNA after injection into the host. In both cases, the defective phages can inject DNA into the host, but cannot replicate. DNA injections by cleavage-sensitive phages result in a montage of phage DNA fragments in infected cells. Irradiation-weakened phages inject and present non-replicative DNA, which can potentially be sampled and acquired by CRISPR arrays. The authors searched for surviving host bacteria, and found that survivors had acquired additional spacers in CRISPR sequences, an indication that the phage DNA was accessible to the CRISPR adaptation machinery (Fig. 1). Although most of the cells died, a fraction of the infected population captured phagegenome pieces in CRISPR sequences. Specifically, the presence of UV-inactivated and RM-susceptible viruses increased the generation of vaccinated bacteria by three- to fourfold and tenfold, respectively, when compared with the presence of functional phages. This

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Genomics: Something to swing about.

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