Convergent origination of aDrosophila-like dosage compensation mechanism in a reptile lineage

Abstract

Sex chromosomes differentiated from different ancestral autosomes in various vertebrate lineages. Here, we trace the functional evolution of the XY Chromosomes of the green anole lizard (Anolis carolinensis), on the basis of extensive high-throughput genome, transcriptome and histone modification sequencing data and revisit dosage compensation evolution in representative mammals and birds with substantial new expression data. Our analyses show that Anolis sex chromosomes represent an ancient XY system that originated at least ≈160 million years ago in the ancestor of Iguania lizards, shortly after the separation from the snake lineage. The age of this system approximately coincides with the ages of the avian and two mammalian sex chromosomes systems. To compensate for the almost complete Y Chromosome degeneration, X-linked genes have become twofold up-regulated, restoring ancestral expression levels. The highly efficient dosage compensation mechanism of Anolis represents the only vertebrate case identified so far to fully support Ohno's original dosage compensation hypothesis. Further analyses reveal that X up-regulation occurs only in males and is mediated by a male-specific chromatin machinery that leads to global hyperacetylation of histone H4 at lysine 16 specifically on the X Chromosome. The green anole dosage compensation mechanism is highly reminiscent of that of the fruit fly, Drosophila melanogaster. Altogether, our work unveils the convergent emergence of a Drosophila-like dosage compensation mechanism in an ancient reptilian sex chromosome system and highlights that the evolutionary pressures imposed by sex chromosome dosage reductions in different amniotes were resolved in fundamentally different ways.

Sex-biased microRNA expression in mammals and birds reveals underlying regulatory mechanisms and a role in dosage compensation

“…In our data, there was considerable potential for coexpression, with 9 of 33 (27%) MMGs with significantly sex-biased expression in mouse heart having at least one intronic member, and the corresponding numbers for mouse liver were 7 sex-biased MMGs of 19 (37%). However, when we compared the sex-biased expression of intronic miRNAs with that of their host genes, based on expression data from Marin et al (2017) (see also Methods), we did not find any significant correlation between miRNA and host gene male-to-female (M:F) ratios in heart, and only a weak correlation in liver, which was no longer significant after correction for multiple tests ( Fig. 2A).…”

“…4A) in all chicken tissues. Although the mir-2954 locus is located within an intron of the XPA gene, XPA is not male-biased to the same extreme degree (Methods; Marin et al 2017). Notably, the male bias of miR-2954-3p is considerably more pronounced (up to almost eightfold in chicken liver) than the maximally twofold difference that is expected between males and females due to gene dosage alone (Lin et al 2014).…”

“…Only protein-coding genes with a minimum expression of 1 FPKM (fragments per kilobase of transcript per million mapped reads) in the tissue of interest were considered based on data from Marin et al (2017). To avoid the frequent false positives associated with functional analyses of miRNA targets (Bleazard et al 2015), we compared targets of sex-biased miRNAs only to targets of unbiased miRNAs instead of to all genes expressed in the tissue of interest (Methods).…”

“…We reasoned that miR-2954-3p, with its strong male bias, broad expression, and preference for Z-linked genes might provide an alternative path to gene-specific dosage compensation. In order to evaluate whether miR-2954-3p regulation is indeed associated with more similar expression patterns in males and females, we calculated M:F ratios for all Z-linked protein-coding genes based on expression data from Marin et al (2017) and compared target genes of miR-2954-3p to target genes of autosomal miRNAs (Methods). Consistent with the dosage compensation hypothesis, we observed significantly smaller M:F ratios for miR-2954-3p targets (Fig.…”

“…Mouse and chicken expression data for protein-coding genes were provided by Marin et al (2017), who performed RNA sequencing for two male and two female individuals and each of the tissues for which we had miRNA data. We calculated M:F ratios for all expressed genes (>1 FPKM in all replicates from a given tissue) with the DESeq2 package (Love et al 2014) based on raw read counts.…”