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Studies Describe Mammalian Y Chromosome Evolution, Recent Stability

NEW YORK (GenomeWeb) – A pair of studies appearing online today in Nature are uncovering evolutionary patterns for the mammalian Y chromosome and revealing conserved Y chromosome sequences stemming from ancestral, dosage-sensitive genes that have acquired functions outside of the male reproductive system, in some cases.

Although the Y chromosome is notorious for gene loss and erosion, the new research suggests that it has remained relatively stable in recent evolutionary history, following a series of early sequence jettisoning events.

In their effort to explore Y chromosome evolution in mammals, researchers from Switzerland and Australia used new and existing genomic and transcriptomic sequences from 15 mammalian species. That data helped them track down more than 130 protein-coding genes on Y chromosomes of the sequenced species, along with more than 150 non-coding RNAs.

By folding in data for additional lineages, the team produced a phylogenetic tree that put the emergence of the mammalian and marsupial Y chromosome ancestor at around 180 million years ago. That so-called therian ancestor carried a version of the male sex chromosome that evolved in parallel with ancestral sex chromosomes in avians and in the monotreme lineage leading to the platypus and spiny anteaters.

Members of that group saw signs of rapid gene loss not long after Y chromosomes cropped up and differentiated in therian and monotreme lineages.

On the other hand, they found that sequences on the diminutive sex chromosome have remained quite stable once the chromosome was whittled down to a core gene set — stability that they attributed, in part, to gene dosage effects.

"[A]lthough some genes evolved novel functions through spatial/temporal expression shifts, most Y genes probably endured, at least initially, because of dosage constraints," senior author Henrik Kaessmann, a researcher affiliated with the University of Lausanne and the Swiss Institute of Bioinformatics, and colleagues wrote.

Likewise, researchers from the Massachusetts Institute of Technology's Whitehead Institute, the Washington University School of Medicine's Genome Institute, and elsewhere found their own evidence for long-term survival of a key set of mammalian Y chromosome genes.

By focusing on ancestral Y linked genes from eight mammalian species using a single-haplotype iterative mapping and sequencing approach, authors of that study determined that human Y chromosome contains 14 of the 18 ancestral genes found on the Y chromosome nearly 100 million years ago.

The team's analysis indicated that no additional ancestral genes have been whittled off of the Y chromosome over the past 44 million years or so.

Moreover, selection seems to have shaped the Y chromosome by maintaining appropriate doses of certain genes with homologues on the X chromosome — particularly genes coding for transcriptional, translational, and protein stability regulators.

Along with Y chromosome gene conservation within mammalian species, the researchers determined that many genes currently found in single copies on the Y chromosome are expressed in range of mammalian tissue types.

That, in turn, hints that Y-linked genes could have more complex roles in health and disease than previously appreciated, perhaps contributing to differential risk for some conditions in males and females.

"This paper tells us that not only is the Y chromosome here to stay, but that we need to take it seriously, and not just in the reproductive tract," senior author David Page, director of the Whitehead Institute, said in a statement.

"There is a clear need to move beyond a unisex model of biomedical research," Page said, "which means we need to move beyond a unisex model of our understanding and treatment of disease."