The human X and Y chromosomes evolved from an ordinary pair of autosomes, but millions of years ago genetic decay ravaged the Y chromosome, and only three per cent of its ancestral genes survived. We reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene content and the selective pressures that preserved the surviving ancestral genes. Our findings indicate that survival was nonrandom, and in two cases, convergent across placental and marsupial mammals. We conclude that the gene content of the Y chromosome became specialized through selection to maintain the ancestral dosage of homologous X–Y gene pairs that function as broadly expressed regulators of transcription, translation and protein stability. We propose that beyond its roles in testis determination and spermatogenesis, the Y chromosome is essential for male viability, and has unappreciated roles in Turner’s syndrome and in phenotypic differences between the sexes in health and disease.

Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators

The peculiar cytology and unique evolution of sex chromosomes raise many fundamental questions. Why and how sex chromosomes evolved has been debated over a century since H.J. Muller suggested that sex chromosome pairs evolved ultimately from a pair of autosomes. This theory was adapted to explain variations in the snake ZW chromosome pair and later the mammal XY. S. Ohno pointed out similarities between the mammal X and the bird/reptile Z chromosomes forty years ago, but his speculation that they had a common evolutionary origin, or at least evolved from similar regions of the genome, has been undermined by comparative gene mapping, and it is accepted that mammal XY and reptile ZW systems evolved independently from a common ancestor. Here we review evidence for the alternative theory, that ZW⇔XY transitions occurred during evolution, citing examples from fish and amphibians, and probably reptiles. We discuss new work from comparative genomics and cytogenetics that leads to a reconsideration of Ohno's idea and advance a new hypothesis that the mammal XY system may have arisen directly from an ancient reptile ZW system.

Relationships between Vertebrate ZW and XY Sex Chromosome Systems

After birds diverged from mammals, different ancestral autosomes evolved into sex chromosomes in each lineage. In birds, females are ZW and males are ZZ, but in mammals females are XX and males are XY. We sequenced the chicken W chromosome, compared its gene content with our reconstruction of the ancestral autosomes, and followed the evolutionary trajectory of ancestral W-linked genes across birds. Avian W chromosomes evolved in parallel with mammalian Y chromosomes, preserving ancestral genes through selection to maintain the dosage of broadly expressed regulators of key cellular processes. We propose that, like the human Y chromosome, the chicken W chromosome is essential for embryonic viability of the heterogametic sex. Unlike other sequenced sex chromosomes, the chicken W chromosome did not acquire and amplify genes specifically expressed in reproductive tissues. We speculate that the pressures that drive the acquisition of reproduction-related genes on sex chromosomes may be specific to the male germ line.

Avian W and mammalian Y chromosomes convergently retained dosage-sensitive regulators

Some ~15.000 angiosperms are dioecious, but mechanisms of sex determination in plants remain poorly understood. In particular, how Y chromosomes evolve and degenerate, and whether dosage compensation evolves as a response, are matters of debate. Here we focus on Coccinia grandis, a dioecious cucurbit with the highest level of X/Y heteromorphy recorded so far. We identified sex-linked genes using RNA sequences from a cross and a model-based method termed SEX-DETector. Parents and F1 individuals were genotyped and the transmission patterns of SNPs then analysed. In the >1300 sex-linked genes studied, X-Y divergence was 0.13 - 0.17, and substantial Y degeneration is implied by an average Y/X expression ratio of 0.63 and an inferred gene loss on the Y of ~40%. We also found reduced Y gene expression being compensated by elevated expression of corresponding genes on the X and an excess of sex-biased genes on the sex chromosomes. Molecular evolution of sex-linked genes in C. grandis is thus comparable to that in Silene latifolia, another dioecious plant with a strongly heteromorphic XY system, and cucurbits are the fourth plant family in which dosage compensation is described, suggesting it might be common in plants.

https://biorxiv.org/content/10.1101/2020.05.22.111070v1.full.pdf

Evidence for dosage compensation in Coccinia grandis, a plant with a highly heteromorphic XY system

Sex chromosomes are usually suppressed for homologous recombination, which leads to the loss of functional genes on the Y or W chromosomes. It remains unclear how species like birds with a ZW sex system cope with the consequential gene expression imbalance, usually in the absence of global dosage compensation mechanism. Here we tackle this conundrum by reporting 14 genes recently transposed from the Z to the W chromosomes of three songbird lineages, after analyzing a total of 12 songbird species’ genomes. These transpositions are estimated to have occurred within 9 million years. Besides the expected signatures of functional degeneration in some genes on the non-recombining W chromosomes, the other retained genes after transposition are enriched for haploinsufficient genes or housekeeping genes. Several genes show biased expression in ovaries of birds or lizard, or function in female germ cells. These results, together with the reported X-to-Y transpositions provide direct evidence that sex-specific and dosage selections may have recurrently driven the restoration of genes on the Y or W chromosomes, and suggest their evolutionary processes are more dynamic than simply becoming completely degenerated.

/pdf/female-specific-and-dosage-selections-restore-genes-through-yxc9tm7rss.pdf

Female-specific and dosage selections restore genes through transpositions onto the degenerated songbird W chromosomes

The evolution of sex chromosome dosage compensation in animals.

The evolution of sex chromosomes in the XY or ZW systems shall lead to gene expression dosage problems, as in at least one of the sexes, the sex-linked gene dose has been reduced by half It has been proposed, most notably by Susumu Ohno for mammals, that the transcriptional output of the whole sex chromosome should be doubled for a complete dosage compensation However, due to the variability of the existing methods to determine the transcriptional differences between Sex chromosomes and Autosomes (S:A ratios) in different studies, whether clade-specific results are comparable and whether there is a more general model to explain dosage compensation states remain unanswered In this study, we collected more than 500 public RNA-seq datasets from multiple tissues and species in major clades (including mammals, birds, fishes, insects, and worms) and proposed a unified computational framework for unbiased and comparable measurement of the S:A ratios of multiple species We also tested the evolution of dosage compensation more directly by assessing changes in the expression levels of the current sex-linked genes relative to those of the ancestral sex-linked genes We found that in mammals and birds, the S:A ratio is approximately 05, while in insects, fishes and flatworms, the S:A ratio is approximately 1 Further analysis showed that the fraction of dosage-sensitive housekeeping genes on the sex chromosome is significantly correlated with the S:A ratio In addition, the degree of degradation of the Y chromosome may be responsible for the change in the S:A ratio in mammals without a dosage-compensation mechanism Our observations offer unequivocal support for the sex chromosome insensitivity hypothesis in animals and suggest that the dosage sensitivity states of sex chromosomes is a major factor underlying different evolutionary strategies of dosage compensation

https://www.biorxiv.org/content/biorxiv/early/2020/07/04/2020.07.04.187476.full.pdf

Menghan Wang

Papers

The evolution of sex chromosome dosage compensation in animals.

The Evolution of Sex Chromosome Dosage Compensation in Animals