Oh No! Ohno's Sex Chromosome Theory Rejected?
Posted by
Alex Berezow at Thu, 05 Jul 2012 20:20:37
The longstanding hypothesis about the evolution of sex chromosomes has just been shaken by a
new paper in the
Proceedings of the National Academy of Sciences.
Female mammals possess two X chromosomes (XX) and males possess one X and one Y chromosome (XY). Compared to the X chromosome, the Y chromosome is small and degraded, which (in general) means that males only have one copy of every X-linked gene. Obviously, it follows that females have two copies of every X-linked gene.
But, from a genetic standpoint, this can be problematic. A condition known as "haploinsufficiency" occurs when one gene is not sufficient for an organism to be healthy. Because genes ultimately produce proteins, having only one copy of a gene may result in a cell producing only half the expected amount of protein. Since the X chromosome contains around 2,000 genes, this means that males face a potential shortage of some 2,000 proteins.
To address this, Susumu Ohno hypothesized in 1967 that gene expression from the X chromosome is doubled. This solves the problem for males, but it creates a brand new problem for females: They would have twice as many proteins as normal. According to Ohno, this dilemma drove evolution toward selecting females which inactivated one X chromosome. "
X-inactivation," in which one X chromosome is "turned off," is a well-documented phenomenon.
For the past 40 years, Ohno's Hypothesis has been indirectly tested by comparing expression from genes on the X chromosome with genes on all the other non-sex chromosomes (called "autosomes"). Some have verified the hypothesis, while others have rejected it. Using a different methodology, the
PNAS paper, which represents the latest addition to the debate, presents an enormous challenge to Ohno's Hypothesis.
The authors compared X-linked gene expression in humans and other mammals with similar genes (called "orthologs") in organisms, such as chickens, which diverged before the origin of mammalian sex chromosomes.
Compared to the similar chicken genes, they found that most X-linked mammalian genes are not doubled in expression. Therefore, the authors conclude that the Ohno Hypothesis is wrong.
This also creates an evolutionary dilemma. If X chromosome gene expression never doubled as Ohno suggested, then what selected for X-inactivation in females? The origin of X-inactivation, previously understood through the lens of Ohno's Hypothesis, is now a complete mystery.
For evolutionary biologists, it might mean heading back to the drawing boards.
Source: Fangqin Lina, Ke Xinga, Jianzhi Zhangb, and Xionglei Hea. "Expression reduction in mammalian X chromosome evolution refutes Ohno's hypothesis of dosage compensation." PNAS 2012, published ahead of print July 2, 2012, doi:10.1073/pnas.1201816109
(Photo: Michael Bodega/Wikimedia Commons)
