Reconstruction and evolutionary history of eutherian chromosomes

Abstract

Whole-genome assemblies of 19 placental mammals and two outgroup species were used to reconstruct the order and orientation of syntenic fragments in chromosomes of the eutherian ancestor and six other descendant ancestors leading to human. For ancestral chromosome reconstructions, we developed an algorithm (DESCHRAMBLER) that probabilistically determines the adjacencies of syntenic fragments using chromosome-scale and fragmented genome assemblies. The reconstructed chromosomes of the eutherian, boreoeutherian, and euarchontoglires ancestor each included >80% of the entire length of the human genome, whereas reconstructed chromosomes of the most recent common ancestor of simians, catarrhini, great apes, and humans and chimpanzees included >90% of human genome sequence. These high-coverage reconstructions permitted reliable identification of chromosomal rearrangements over ∼105 My of eutherian evolution. Orangutan was found to have eight chromosomes that were completely conserved in homologous sequence order and orientation with the eutherian ancestor, the largest number for any species. Ruminant artiodactyls had the highest frequency of intrachromosomal rearrangements, and interchromosomal rearrangements dominated in murid rodents. A total of 162 chromosomal breakpoints in evolution of the eutherian ancestral genome to the human genome were identified; however, the rate of rearrangements was significantly lower (0.80/My) during the first ∼60 My of eutherian evolution, then increased to greater than 2.0/My along the five primate lineages studied. Our results significantly expand knowledge of eutherian genome evolution and will facilitate greater understanding of the role of chromosome rearrangements in adaptation, speciation, and the etiology of inherited and spontaneously occurring diseases.

Keywords: ancestral genome reconstruction; chromosome evolution; genome rearrangements.

Fig. 1.

Phylogenetic tree of descendant species and reconstructed ancestors. The numbers on branches from the eutherian ancestor to human are the numbers of breakpoints in RACFs, with breakpoint rates (the number of breakpoints per 1 My) in parentheses. The unit of time of branch lengths is 1 My. The details of the genome assemblies of descendant species and the classification of rearrangements are shown in SI Appendix, Tables S1 and S3, respectively.

Fig. 2.

Summary visualization of rearrangements of ancestral eutherian chromosomes in chromosomes of reconstructed descendant ancestors, and extant descendant and outgroup species. Solid red-brown blocks indicate eutherian chromosomes that were maintained as a single synteny block, with shades of the color indicating the fraction of the chromosome affected by intrachromosomal rearrangements (lightest shade is most affected). Split blocks demarcate eutherian chromosomes that were also affected by interchromosomal rearrangements: that is, fissions and translocations. Shades of green in split blocks indicate the fraction of an ancestral chromosome affected by translocations or fissions (lightest shade is most affected), and the shades of red-brown indicate the fraction of eutherian chromosomes affected by intrachromosomal rearrangements measured and summed for all SFs. The heatmap shows the color shades used to represent different fractions of outgroup, descendant ancestors’ and extant species chromosomes affected by interchromosomal (shades of green) or intrachromosomal (shades of brown-red) rearrangements. Because of undefined positions of ancestral centromeres, the intrachromosomal rearrangements are measured relative to the prevailing orientation of SFs within each outgroup or descendant chromosome and therefore the fraction of intrachromosomal rearrangements cannot exceed 50%. As it follows from the heatmap, dark shades indicate high level of conservation with the ancestral chromosome and light shades of the same color indicate high level of rearrangements. BOR, boreoeutherian ancestor; CAT, catarrhini ancestor; EUA, euarchontoglires ancestor; EUT, eutherian ancestor; GAP, great apes ancestor; HUC, human–chimp ancestor; SIM, simian ancestor.

Fig. 3.

Two examples of eutherian ancestor chromosomes with dramatically different evolutionary histories in the primate lineage. Order and orientation of SFs overlaid on the reconstructed eutherian ancestor chromosomes are visualized using the Evolution Highway comparative chromosome browser (eh-demo.ncsa.illinois.edu/ancestors/). The eutherian chromosome number and its total length are given at the top of each ideogram. Only the main fragment of EUT15 (EUT15a) is shown for this comparison. Blue and pink colors represent orientation of blocks relative to the reference, with blue indicating the same orientation, and pink indicating the opposite orientation. Pink does not always indicate an inversion because the orientation of RACFs is randomly chosen during the reconstruction. Also, as in the case of dog for EUT14, numbering of nucleotides may begin from the opposite end of the chromosome. The number within each block represents a chromosome of a reconstructed ancestor (Dataset S1) or an extant species; a letter indicates a fragment of the chromosome. Adjacency scores computed with DESCHRAMBLER are shown in the right-most tracks. Letter codes of reconstructed ancestors are the same as given in the legend of Fig. 2. Only extant species with full chromosome-scale assemblies are shown. BOR, boreoeutherian ancestor; CAT, catarrhini ancestor; EUA, euarchontoglires ancestor; GAP, great apes ancestor; HUC, human–chimp ancestor; SIM, simian ancestor.