Bird and mammal sex-chromosome orthologs map to the same autosomal region in a salamander (ambystoma)

Abstract

We tested hypotheses concerning the origin of bird and mammal sex chromosomes by mapping the location of amniote sex-chromosome loci in a salamander amphibian (Ambystoma). We found that ambystomatid orthologs of human X and chicken Z sex chromosomes map to neighboring regions of a common Ambystoma linkage group 2 (ALG2). We show statistically that the proportion of human X and chicken Z orthologs observed on ALG2 is significantly different from the proportion that would be expected by chance. We further show that conserved syntenies between ALG2 and amniote chromosomes are identified as overlapping conserved syntenies when all available chicken (N = 3120) and human (N = 14,922) RefSeq orthologs are reciprocally compared. In particular, the data suggest that chromosomal regions from chicken chromosomes (GGA) Z and 4 and from human chromosomes (HSA) 9, 4, X, 5, and 8 were linked ancestrally. A more distant outgroup comparison with the pufferfish Tetraodon nigroviridis reveals ALG2/GGAZ/HSAX syntenies among three pairs of ancestral chromosome duplicates. Overall, our results suggest that sex chromosomal regions of birds and mammals were recruited from a common ancestral chromosome, and thus our findings conflict with the currently accepted hypothesis of separate autosomal origins. We note that our results were obtained using the most immediate outgroup to the amniote clade (mammals, birds, and other reptiles) while the currently accepted hypothesis is primarily based upon conserved syntenies between in-group taxa (birds and mammals). Our study illustrates the importance of an amphibian outgroup perspective in identifying ancestral amniote gene orders and in reconstructing patterns of vertebrate sex-chromosome evolution.

Figure 1.—

An abridged phylogeny of the major groups of bony vertebrates. Divergence times were obtained from the literature (Kumar and Hedges 1998; Ruta et al. 2003) Birds represent an ancient reptile lineage that diverged from other reptilian groups ∼220 MYA (Kumar and Hedges 1998).

Figure 2.—

A comparative map of Ambystoma LG2 and syntenic chromosomes from humans and chickens. Vertical bars within ALG2 represent the position of Ambystoma transcripts that yielded an alignment in either the human or the chicken genome. ALG2 loci that do not correspond to orthologs on GGA Z and 4 or on HSA 4, 5, 8, 9, and X are highlighted in green. Red lines connect human/Ambystoma orthologies and blue lines connect chicken/Ambystoma orthologies. The sex chromosomes of human (X) and chicken (Z) are both syntenic with Ambystoma LG2.

Figure 3.—

A comparative map of the human and chicken chromosomes that are syntenic with Ambystoma LG2. Vertical bars within chromosomes represent the position of mapped human RefSeq transcripts or chicken orthologs. Lines connect the positions of human/chicken orthologies. Bars above human chromosomes show the proportions of chicken chromosome orthologs that were identified within a given segment, and bars below chicken chromosomes show the proportions of human chromosome orthologs that were identified within a given segment. Note that the chicken chromosomes Z and 4 map to adjacent and overlapping regions of HSA8 and HSA5.

Figure 4.—

Oxford plot of the position of amniote sex-chromosome loci in the T. nigroviridis genome. The y-axis represents the relative position of orthologs on human (HSA) and chicken (GGA) chromosomes. The x-axis represents the relative position of orthologs on T. nigroviridis chromosomes. “H”, “A,” and “B” correspond to preduplicated ancestral chromosomes (Jaillon et al. 2004). Cells containing an excess of orthologies are highlighted in red (P < 0.005) and yellow. Cells containing a deficiency of orthologies are highlighted in blue (P < 0.005) and green.