Functionally Degenerate--Y Not So?

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Science  04 Jan 2008:
Vol. 319, Issue 5859, pp. 42-43
DOI: 10.1126/science.1153482

Genetic and theoretical studies of Y chromosomes have led to the conclusion that they evolve to become functionally degenerate. For example, in the fruit fly Drosophila melanogaster, a century of genetic research on its Y chromosome indicates that it codes for few traits besides a small number of male fertility factors (1). On page 91 of this issue (2), Lemos et al. change this perception of functional paucity by showing that the Y chromosome of D. melanogaster regulates the activity of hundreds of genes harbored on other chromosomes.

The theoretical rationale for the evolution of a degenerate Y chromosome is based on its lack of recombination, the process by which corresponding DNA segments are exchanged between homologous chromosomes, thus producing new genetic combinations. When a primitive Y chromosome stops recombining, the efficiency of natural selection drops substantially because selection cannot act independently on different Y-linked mutations. This slows the accumulation of beneficial mutations and speeds that of mildly deleterious ones. As a consequence, the fitness of a Y-linked gene wanes relative to its X-linked homolog, and it can ultimately become silenced by persistent accumulation of deleterious mutations—a result made possible because of redundancy to its X-linked homolog. Gene silencing can also be selectively favored when a Y-linked null mutation (one that results in the absence of a gene product) increases fitness because it does not interfere with the expression of its fitter X-linked homolog.

Gene expression in males.

A mutation in D. melanogaster that influences gene expression in males experiences selection in the male fly most often when it is Y-linked (Y), least often when X-linked (X), and at an intermediate level when located on the autosomes (A).


Lemos et al. now challenge this evolutionary view of a continually decaying Y chromosome. The authors collected Y chromosomes from D. melanogaster spanning different latitudes and subspecies across Africa and North America so as to maximize functional polymorphism, and then substituted each one for the Y chromosome in a single fly strain (ensuring an otherwise common genetic background). They then screened a nearly genomewide set of genes and looked for differences in gene expression in response to the substituted Y chromosome. Because of high statistical error rates when thousands of genes are scored simultaneously, it is difficult to estimate the exact number of affected genes, but the estimates are surprisingly high, ranging from around 100 up to about 1000 (D. melanogaster is estimated to have ∼13,000 genes).

Lemos et al. also detected several coherent patterns among the Y-regulated genes. The Y chromosome influences the expression of genes that are more strongly expressed in males. Genes regulated by the Y chromosome are also more strongly influenced by environmental stress (heat shock), and many are associated with sperm development. Genes that influence the mitochondria are also overrepresented in the pool of genes regulated by the Y chromosome. In addition, affected genes are more evolutionarily dynamic in terms of polymorphisms for gene expression within the species, and more diverged from a closely related congener (Drosophila simulans).

It is now well established that a large proportion of the genome is expressed at different levels in males and females in many organisms (3), and the patterns found by Lemos et al. fit well with what would be expected for Y-linked regulatory genes. Whereas the Y chromosome spends every generation in males, the X chromosome and autosomes alternate between the sexes across generations. A mutation favoring males that is located on the X chromosome or autosomes can therefore only accumulate when selection in females is concordant, absent, or not too strongly discordant (4). However, this restriction is removed for Y-linked mutations because there can be no counterselection in females. Even when a mutation results in a phenotype that is exclusive to males, it will have an advantage if Y-linked because, unlike the X chromosome and autosomes, the Y chromosome is expressed (and hence selected) in males every generation (see the figure). The Y chromosome therefore represents a favorable platform for mutations that improve male gene expression.

As many Y-linked genes have degenerated, should we expect the Y chromosome to inevitably be lost altogether? Not necessarily. As the number of functional genes on the Y chromosome declines, the efficacy of natural selection increases on the remaining genes. Decay of the Y chromosome therefore slows down over time and can ultimately stop altogether. The fitness advantage of a highly degenerated Y chromosome is illustrated by Drosophila afinis in which the Y chromosome is not required for fertility. In this species, males with no Y chromosome (XO) sire 25 to 38% fewer offspring when competing with XY males (5). The study by Lemos et al. provides a mechanism for the large fitness advantage of XY males, even when vital fertility factors are absent on the Y chromosome: The Y chromosome has evolved to become a major regulator of gene expression in males.

If the Y chromosome is such a strong regulator of genes in males, then why have past studies found so few Y-linked traits in humans and flies? The Y chromosome may have evolved to modulate rather than turn on or turn off gene expression. Its effects may therefore be continuous rather than discrete and thus more difficult to detect than the more distinct phenotypes associated with loss-of-function mutations. As the power of quantitative trait locus analysis increases, the phenotypic manifestations of the genes regulated by the Y chromosome discovered by Lemos et al. may become more apparent.

The next stage in understanding the newly discovered regulatory powers of the Drosophila Y chromosome will be to characterize the genetic mechanism(s) underlying their influence. It will also be interesting to see, in flies and other species, whether genomic components that are only transmitted through the matriline (mitochondria and cytoplasmic endosymbionts) have evolved to strongly influence gene expression in females. The study by Lemos et al. further suggests that it will be important to test whether the human Y chromosome also has evolved to become a regulatory giant.

References and Notes

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