Gibbon genome and the fast karyotype evolution of small apes

Gibbons are small apes living in southeast Asia that diverged between Old Monkeys and great apes and whose most distinctive feature is the high rate of evolutionary chromosomal rearrangement.

The aim of this study was threefold: First, the authors looked into the mechanisms that could explain the extraordinary rate of chromosomal rearrangement of gibbons. Second, they explored their evolutionary history to shed light into the timing and order of splitting of the gibbon genera. Third, they looked into the functional evolution of genes that might be associated with gibbon-specific adaptations.

To do so, they sequenced and assembled the genome of the white-cheeked gibbon (Nomascus leucogenys), showing that the quality and statistics of the assembled genome was comparable to that of other primates (Table 1 and Fig.S1).


Chromosomal rearrangement and LAVA insertions

Chromosomal rearrangement was confirmed by comparing the karyotype of the assembled Gibbon genome (Nleu1.0) to that of human. Figure 2A shows the extraordinarily high number of rearrangements compared to other primates. Furthermore these reshuffling events affect long stretches of chromosomes (displayed in Fig.2A are collinear blocks larger than 10Mb), whereas short-scale rearrangement events occur at levels comparable to other primates (Fig.2B).

Since the four Gibbon genera of this study differ themselves in chromosome number (ranging from 38 to 52), it would be interesting to have also a global view of the large-scale chromosomal rearrangement of the other genera compared to human, as well as the differences in karyotype among the four species.

Next the authors classified the 94 identified gibbon-human synteny breakpoints in two classes, depending on whether the breakpoint could be defined at base-pair level or at interval level (exemplified in Fig.2C). In the latter case, authors observed that repetitive sequences tend to accumulate at the synteny intervals.

In order to investigate the possible mechanism underlying the increased rate of chromosomal reshuffling, Carbone et al. searched for LAVA insertions in the gibbon genome. LAVA elements are retrotransposons unique to gibbons, with a structure that combines parts of other repeats (Fig. 3A). More than 1200 functional LAVA insertions were found in the assembled genome, of which a significant proportion overlap with genes related to chromosome segregation. Moreover LAVA elements were found to lie within introns and mostly in the antisense orientation.

In a series of reporter assays using a luciferase construct in which the transcription termination site has been replaced with the 3’ end of LAVA elements (LAVA_E or LAVA_F, Fig.3B) in antisense orientation, the authors showed that the termination site provided by the LAVA element can cause the premature termination of the transcript (Fig.3B). However this was the case for only one of the two constructs (LAVA_F but not LAVA_E). Given the presence of several subfamilies of LAVA elements (as illustrated in Fig.3C) it would then be interesting to see if their hypothesis of intronic antisense LAVA insertions causing early transcription termination in genes related to chromosome segregation holds for more of these elements or whether LAVA_F and not LAVA_E elements are specifically enriched in the genes of interest.


Evolutionary history of gibbons

In order to study gibbon phylogeny and demography, Carbone et al. sequenced the genomes of two individuals from each genus (Nomascus, Hylobates, Hoolock, Symphalangus, see figure 1 for geographic distribution) to a medium coverage and constructed phylogenetic trees by UPGMA and ABC analyses. At least three UPGMA trees are observed with similar frequency (Fig.4A), therefore leaving still open the debate of the splitting order of the genera.

On the other hand, the short length of the internal branches in the best phylogenetic tree is suggestive of a fast speciation process, or even a nearly instantaneous appearance of all four genera around 5 millions years ago (Fig.4B) that would explain the difficulty to discern the order and timing of speciation.


Functional genome evolution

Carbone et al. found 240 short regions with and increased substitution rate, a proxy of adaptive and functional evolution. Moreover these regions co-localized in genes containing LAVA elements and therefore enriched for chromosome segregation-related pathways. The authors hypothesized that, similar to humans, these hotspots of accelerated substitutions can have a functional role by modulating the transcriptional termination of LAVA insertions. However, it is important to notice that the functional relevance of such accelerated regions in human is still a matter of debate.

Finally the study revealed the positive selection, solely in gibbons, of a series of genes responsible for the specific features of these animals, such as the longer and powerful arm muscles.

In summary, the fundamental finding of this study is the presence of gibbon-specific LAVA insertions in genes responsible for chromosome organization which, although it does not prove causality, provides an interesting and plausible molecular mechanisms that would explain the strikingly high rate of large chromosomal rearrangements observed in these species.

Carbone, L., Alan Harris, R., Gnerre, S., Veeramah, K., Lorente-Galdos, B., Huddleston, J., Meyer, T., Herrero, J., Roos, C., Aken, B., Anaclerio, F., Archidiacono, N., Baker, C., Barrell, D., Batzer, M., Beal, K., Blancher, A., Bohrson, C., Brameier, M., Campbell, M., Capozzi, O., Casola, C., Chiatante, G., Cree, A., Damert, A., de Jong, P., Dumas, L., Fernandez-Callejo, M., Flicek, P., Fuchs, N., Gut, I., Gut, M., Hahn, M., Hernandez-Rodriguez, J., Hillier, L., Hubley, R., Ianc, B., Izsvák, Z., Jablonski, N., Johnstone, L., Karimpour-Fard, A., Konkel, M., Kostka, D., Lazar, N., Lee, S., Lewis, L., Liu, Y., Locke, D., Mallick, S., Mendez, F., Muffato, M., Nazareth, L., Nevonen, K., O’Bleness, M., Ochis, C., Odom, D., Pollard, K., Quilez, J., Reich, D., Rocchi, M., Schumann, G., Searle, S., Sikela, J., Skollar, G., Smit, A., Sonmez, K., Hallers, B., Terhune, E., Thomas, G., Ullmer, B., Ventura, M., Walker, J., Wall, J., Walter, L., Ward, M., Wheelan, S., Whelan, C., White, S., Wilhelm, L., Woerner, A., Yandell, M., Zhu, B., Hammer, M., Marques-Bonet, T., Eichler, E., Fulton, L., Fronick, C., Muzny, D., Warren, W., Worley, K., Rogers, J., Wilson, R., & Gibbs, R. (2014). Gibbon genome and the fast karyotype evolution of small apes Nature, 513 (7517), 195-201 DOI: 10.1038/nature13679

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