A comprehensive molecular cytogenetic analysis of chromosome rearrangements in gibbons

Abstract

Chromosome rearrangements in small apes are up to 20 times more frequent than in most mammals. Because of their complexity, the full extent of chromosome evolution in these hominoids is not yet fully documented. However, previous work with array painting, BAC-FISH, and selective sequencing in two of the four karyomorphs has shown that high-resolution methods can precisely define chromosome breakpoints and map the complex flow of evolutionary chromosome rearrangements. Here we use these tools to precisely define the rearrangements that have occurred in the remaining two karyomorphs, genera Symphalangus (2n = 50) and Hoolock (2n = 38). This research provides the most comprehensive insight into the evolutionary origins of chromosome rearrangements involved in transforming small apes genome. Bioinformatics analyses of the human-gibbon synteny breakpoints revealed association with transposable elements and segmental duplications, providing some insight into the mechanisms that might have promoted rearrangements in small apes. In the near future, the comparison of gibbon genome sequences will provide novel insights to test hypotheses concerning the mechanisms of chromosome evolution. The precise definition of synteny block boundaries and orientation, chromosomal fusions, and centromere repositioning events presented here will facilitate genome sequence assembly for these close relatives of humans.

Figure 1.

Two distinct ideograms for each of the 18 HLE autosomes. The ideogram on the left reports the synteny block arrangement with respect to the Hylobatidae ancestral karyotype (HyA) reported in Figure 3, to which the colors also refer. The one on the right reports the homologous human blocks. For details, see Supplemental Table ST2 or the website http://www.biologia.uniba.it/hoolock. This figure also reports the fusion points, the evolutionary new centromeres (ENC), and inactivated centromeres.

Figure 2.

Two distinct ideograms for each of the 24 SSY autosomes. The ideogram on the left reports the synteny block arrangement with respect to the Hylobatidae ancestral karyotype (HyA), reported in Figure 3, to which the colors also refer. The one on the right reports the homologous human blocks. For details see Supplemental Table ST3 or the website http://www.biologia.uniba.it/siamang. This figure also reports the fusion points, the evolutionary new centromeres (ENC), and inactivated centromeres.

Figure 3.

Hylobatidae ancestral karyotype (HyA). The chromosomes on the right report the human chromosomes contributing to each HyA chromosome. In most cases, HyA chromosomes are a mosaic of various fragments of human chromosomes. These details, not annotated in the Figure, are reported in Supplemental Table ST4.

Figure 4.

Enrichment of genomic features in breakpoint regions. Permutation tests were used to assess the overlap between the gibbon breakpoints and genomic features. (A) Segmental duplications; (B) Alu elements; and (C) SVA elements. The black vertical line indicates the observed value for the breakpoints identified in the study. In all three cases it is evident that the genomic features have a higher overlap with the breakpoints than one could expect by chance.

Figure 5.

The ellipse in the middle shows the four chromosomes (6, 8, 9, and 18) hypothesized to be heterozygous for variant forms in the HyA. (Arrows) Segregations of each variant chromosome in the four genera. The table at the bottom makes clear the conflicting results generated by the grouping of the four genera when the variant forms are separately considered.