Deeply conserved synteny and the evolution of metazoan chromosomes

Abstract

Animal genomes show networks of deeply conserved gene linkages whose phylogenetic scope and chromosomal context remain unclear. Here, we report chromosome-scale conservation of synteny among bilaterians, cnidarians, and sponges and use comparative analysis to reconstruct ancestral chromosomes across major animal groups. Comparisons among diverse metazoans reveal the processes of chromosome evolution that produced contemporary karyotypes from their Precambrian progenitors. On the basis of these findings, we introduce a simple algebraic representation of chromosomal change and use it to establish a unified systematic framework for metazoan chromosome evolution. We find that fusion-with-mixing, a previously unappreciated mode of chromosome change, has played a central role. We find that relicts of several metazoan chromosomal units are preserved in unicellular eukaryotes. These conserved pre-metazoan linkages include the chromosomal unit that encodes the most diverse set of metazoan homeobox genes, suggesting a candidate genomic context for the early diversification of this key gene family.

Fig. 1.. Anciently conserved synteny across bilaterians, sponge, and cnidarians.

(Right) Numbered horizontal bars represent the chromosomes of five species. (Left) Phylogenetic tree is shown with the root marked by a black circle. Sponge is shown in a central location to display conserved syntenies with both bilaterians (top) and cnidarians (bottom). Common names and three-letter acronyms for each species are shown (see text for details). On the right, colored vertical lines connect orthologous genes across the five species. Only connections between chromosome pairs with significantly enriched conservation of synteny are shown. Each color represents a distinct ALG, as listed in Fig. 3. Two or more colors converging on a chromosome (e.g., amphioxus BFL5 and hydra HVU6) indicate fusion-with-mixing of ancestral units. See also Fig. 4.

Fig. 2.. Pairwise dot plots and chromosome-chromosome significance.

(Top) Dot plots showing the ordinal location of orthologous genes between jellyfish and amphioxus (left) and sponge (right). Genes with orthologs are numbered consecutively without regard to distance. (Bottom) Sponge versus amphioxus dot plot (left) and chromosome-chromosome significance by Fisher’s exact test (right). In dot plots, colored dots represent genes with consistent statistically significant conserved chromosomal synteny as shown in Figs. 1 and 3; genes of variable synteny are shown in gray. n.s., not significant.

Fig. 3.. Correspondence between ALGs and chromosomes of contemporary organisms.

Bold indicates direct association with ALG. Note that BFL3R (shaded gray) represents a single unit split to better indicate relationships with other species.

Fig. 4.. Elementary algebraic operations underlying metazoan chromosome dynamics.

Left: Cartoon of chromosomal translocations. Right: The resulting dot plot. (A) Syntenic equivalence, i.e., conserved synteny without regard to colinearity, denoted symbolically by ≡. (B) Robertsonian translocation in which two chromosomes “fuse” without mixing, with stable boundary denoted symbolically by ●. Robertsonian fusions are reversible if no mixing has occurred. This diagram may also describe end-to-end fusions. (C) Centric insertion in which one chromosome is inserted into another, denoted symbolically by ↘. (D) Fusion-with-mixing in which the genes of two chromosomes are brought together (by either Robertsonian or end-to-end translocation or centric insertion) and, through a series of intrachromosomal rearrangements, become interspersed, denoted symbolically by ⊗. Both (C) and (D) are irreversible changes. Dotted gray arrows in (B) and (C) show the result of large-scale inversions that cross fusion boundaries. Note that in (B), the distal segments have different ancestry, while in (C), they have the same ancestry. (E) Phylogenetic inference using chromosomal characters. When chromosomes of two lineages are in 1:1 correspondence (e.g., the top two lineages in this rooted three-taxon tree), their shared syntenic configuration must be ancestral to the entire clade. Internal branches (bottom lineage) that show genes of these ALGs interspersed on the same chromosome are said to be fused-and-mixed.

Fig. 5.. Chromosome evolution in metazoan lineages.

Phylogenetic distribution of chromosome changes in (A) early bilaterian-cnidarian-sponge divergence, (B) spiralians, (C) cnidarians, and (D) chordates. All ancestral states and changes are inferred from genome comparisons and reconstructions as described in the text. ALGs not shown on branches retain ancestral state. Algebraic symbols are defined in Fig. 4 and in the text. Blue starbursts represent whole-genome duplications. Note that prior rearrangements in the indicated ancestor are denoted in shorthand, e.g., A1bB3 represents the cnidarian ancestral state A1b⊗B3 and B1B2 represents B1⊗B2.

Fig. 6.. Significant associations between BCS ALG and scaffolds of three unicellular holozoans imply deep ancestry of BCS linkage groups.

(Top) Filasterean amoeba C. owczarzaki. (Middle) Colony-forming choanoflagellate S. rosetta. (Bottom) Solitary choanoflagellate M. brevicollis. For each species, P values are Bonferroni-corrected for the number of scaffolds tested against the BCS ALGs for conserved synteny (Materials and Methods). Circle size corresponds to the number of shared genes.