Kaessmann Lab

Congrats Gray and all!! So cool to see that this fantastic work is out now!

…and yes, they do - your miR-17~92 story is also very cool..

…and congrats to you, Magdalena and Fany et al. on the wonderful bat study, which I saw is out in NEE now!!

Many thanks Dario!! Hope all is well!

Thanks so much Leo! All the best

Thank you!

Thank you!

Many thanks Arnau!

Many thanks Sergio!

Thanks a lot Arnaud!

Many thanks Axel!

Thank you very much!!

Many thanks Uri!

A male-essential miRNA is key for avian sex chromosome dosage compensation - Nature Birds have evolved a unique sex chromosome dosage compensation mechanism involving the male-biased microRNA (miR-2954), which is essential for male survival by regulating the expression of dosage-sens...

@kaessmannlab.bsky.social has for the first time shown in an international collaboration, that survival of male birds crucially depends on a micro RNA for sex chromosome dosage compensation. The paper just has been published by Nature.
www.nature.com/articles/s41...

Thanks so much Margarida for your (as usual) invaluable contributions!!

How a Tiny Gene Ensures the Survival of Male Birds – Researchers from Heidelberg and Edinburgh identify a mechanism that balances the genetic disparity between sex chromosomes
www.uni-heidelberg.de/en/newsroom/...

Many thanks Fillip!!

Thanks so much Edda!! Many thanks also for your comment in the Research Briefing and the invaluable comments (we assume ;-)) on the paths to publication... Best!

While the silencing mechanism in mammals involves a transcriptional shutdown of most of the X chromosome, birds evolved a highly targeted post-transcriptional mechanism that specifically silences upregulated dosage sensitive Z-linked genes.

These mechanisms, however, show striking differences, although they all involve noncoding RNAs as key mediators (miR-2954 in birds; the long noncoding RNAs XIST and RSX in placentals and marsupials, respectively) and are essential for the viability of the homogametic sex.

That is, the decay of the sex chromosome specific to the heterogametic sex (the W or Y) triggered upregulation of the sex chromosome common to both sexes (the Z or X), necessitating the evolution of secondary silencing mechanisms in male (ZZ) birds and female (XX) mammals.

The avian ZW dosage compensation system thus has key parallels to the XY system of therian mammals and the original famous hypotheses for the evolution of dosage compensation by Susumu Ohno (1967).

We finally show that miR-2954 originated in the common ancestor of birds 108-245 million years ago, that its sequence has since been fully conserved across birds, and that other aspects of miR-2954-mediated dosage compensation have been conserved as well.

2) The resulting excess of transcripts in males resulting from the combined activity of two dosage-sensitive Z gene copies was in turn offset by the emergence of a highly targeted miR-2954-mediated transcript degradation mechanism during avian evolution.

1) Evolutionary pressures on females following W gene loss led to the evolution of transcriptional and translational upregulation of dosage-sensitive Z-linked genes in females – but also their transcriptional upregulation in males.

Together, our observations support a scenario for the evolution of dosage compensation in birds:

Our evolutionary gene expression analyses further revealed that these dosage-sensitive target genes have become upregulated on the single Z in female birds during evolution.

We find that Z-linked targets of miR-2954 are highly enriched for broadly expressed dosage-sensitive genes, which likely explains the lethal phenotype observed in homozygous knockout males.

We demonstrate that miR-2954 specifically targets Z-linked genes and that, therefore, its removal from the chicken genome leads to the upregulation of hundreds of genes on the Z chromosome – with lethal consequences in homozygous male knockout embryos.