Sex chromosome conflict

30 October 2012

NIMR researchers and collaborators have demonstrated an intragenomic conflict between the X and Y chromosomes in mice.

Intragenomic conflicts arise when a genetic element favours its own transmission to the detriment of others. Normally both copies of a gene have an equal chance of being inherited. However, some genes can act “selfishly” and are transmitted to more than 50% of offspring. This phenomenon is known as transmission distortion. Distorting genes that are present on the X or Y chromosome will lead to an excess of female/male offspring respectively. This then sets up a “genomic conflict” (arms race) between the sex chromosomes that can radically affect their gene content. Male mice that have lost part of their Y chromosome produce more than 50% female offspring and show over-activation of multiple genes on the X chromosome. This provides strong circumstantial evidence for distortion. In the mouse, the existence of an intragenomic conflict between X- and Y-linked multicopy genes has long been suggested but never demonstrated.

Julie Coquet, previously worked in the lab of Paul Burgoyne (pictured) in the Division of Stem Cell Biology and Developmental Genetics, but is now working in Paris. She has demonstrated, with substantial input from Peter Ellis at the University of Cambridge, the existence of a genomic conflict regulated by the genes Slx/Slxl1 and Sly. The SLX/SLXL1 and SLY proteins have antagonistic effects on sex chromosome expression in developing sperm and skew the offspring sex-ratio in favor of females/males. Interestingly, while a deficiency of either gene alone leads to severe fertility problems, fertility is improved when both genes are deficient.

Julie’s data show that Slx/Slxl1 and Sly have antagonistic effects during sperm differentiation and are involved in a postmeiotic intragenomic conflict that causes segregation distortion and male sterility. This is undoubtedly what drove the massive gene amplification on the mouse X and Y chromosomes. To the best of our knowledge, her work is the first demonstration of a competition occurring between X and Y related genes in mammals. It also provides a biological basis for the concept that intragenomic conflict is an important evolutionary force which impacts on gene expression, genome structure, and speciation.

Paul Burgoyne

The finding that a few novel genes control epigenetic regulation of a key step in spermatogenesis is quite remarkable. these findings help to illustrate the power of evolution to generate novelty in the face of developmental constraint and call into question the notion that research on a few model systems will be sufficient to elucidate the general molecular underpinnings of reproduction.

Jeffrey Good, in his Perspective article

Click image to view at full-size

Model presenting how SLX/SLXL1 and SLY proteins have antagonistic effects in the spermatid nucleus and cytoplasm.

Original article

Julie Cocquet, Peter J. I. Ellis, Shantha K. Mahadevaiah, Nabeel A. Affara, Daniel Vaiman, Paul S. Burgoyne (2012

A Genetic Basis for a Postmeiotic X Versus Y Chromosome Intragenomic Conflict in the Mouse.

PLOS Genetics 8(9): e1002900. Full-text.

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