Repeated Evolution of Transcript Dosage Compensation of Independently Formed Nematode Neo-X Chromosomes

Ohno proposed that, during the origin of X/Y sex chromosomes from a pair of autosomes, X-linked genes must double their per-allele expressions to compensate for the degeneration of their Y homologs. Whether Ohno's hypothesis holds in the nematode Caenorhabditis elegans remains unresolved despite that C. elegans is a model for studying between-sex X chromosome dosage compensation. Genome sequencing revealed independent fusions of an ancestrally autosomal linkage group to the X chromosome in C. elegans and Brugia malayi, two species belonging to different suborders of the order Rhabditida, allowing testing Ohno's hypothesis in repeated origins of neo-X chromosomes from the same autosomal linkage group. For each C. elegans X-linked gene and its autosomal ortholog in Pristionchus pacificus, we computed the X:AA ratio in transcript level and observed a median of ∼1. The same is true for B. malayi X-linked genes when compared with their autosomal orthologs in Dirofilaria immitis. We find a significant enrichment of presumably dosage-sensitive transcription factor genes among the autosomal genes of P. pacificus (or D. immitis) that become X-linked in C. elegans (or B. malayi), but the results are mixed for other groups of presumably dosage-sensitive genes, providing a partial support to the hypothesis that X upregulation depends on the prevalence of dosage-sensitive genes in the proto-X. We conclude that, unlike the virtual absence of X upregulation at the transcript level in eutherian mammals, Ohno's hypothesis is strongly supported in both nematode lineages investigated.