Rapid Evolution of Genes on the Human X Chromosome


There is considerable interest in determining the sequences that are evolving rapidly in our genome, as these may well confer an advantage that has helped to propel the evolution of our species. Owing to sex chromosome‐specific modes of natural selection, genes on the human X chromosome are evolving rapidly in comparison to genes located on autosomes. However, it is not clear to what extent these loci are evolving adaptively or due to other molecular (mutation and recombination) and evolutionary (selection and drift) processes. Biological factors in addition to selection could contribute to elevated rates, such as the evolutionary history and genomic features of the X chromosome. Additionally, genes on the X are distributed in a nonrandom fashion, potentially influencing their evolution. Furthermore, the function and expression profile of each X‐linked gene may play a role in determining its evolutionary rate. Recent technological advances have provided rich datasets for the investigation and unravelling of these confounding factors.

Key Concepts:

  • The human X chromosome is a compilation of biological contradictions: it is remarkably conserved in gene content between species, while being highly diverged from its Y counterpart; it is present in twice as many copies in females than males, and yet enriched for genes with male‐biased expression.

  • The theory of fast‐X evolution is based on the observation that genes on the X in XY males will be more easily targeted by natural selection, thus accelerating the rate of adaptive evolutionary change for beneficial mutations.

  • Many genes on the X tend to evolve more slowly than their Y counterparts, due to the higher mutation rate in the male germline.

  • Genes on the X are likely to be involved in reproduction, sex biased in their expression profile and tissue‐specific in nature – each of these factors has been linked to accelerated rates of sequence and/or expression divergence independently of the fitness advantage of the associated allele.

  • Although fast‐X has been observed in different taxa, the relative contribution of the underlying evolutionary forces (selection for advantageous mutations versus drift of slightly deleterious mutations) can be very different between species.

Keywords: sex chromosomes; evolutionary rates; positive selection; sex‐biased genes; Fast‐X

Figure 1.

Major stages of the evolutionary history of the human X chromosome. First, one of a pair of freely recombining ancestral autosomes acquired a sex‐determining locus (black bar) thereby establishing genetic sex determination. Next, recombination was locally suppressed surrounding the sex determining locus to protect it from the effects of reshuffling. Following the loss of recombination, the proto‐X and proto‐Y began to diverge via accumulating mutations (e.g. inversions, substitutions and indels) on the Y, thus leading to X‐ and Y‐specificity. This oldest region of homology between the ancient X and Y is known as the X‐conserved region (XCR), due to its conservation of gene content and order across the mammalian taxa. A subsequent translocation from additional autosomal sequence known as the X‐added region (XAR) increased the amount of homologous sequence able to recombine between the progressively more diverged pair of chromosomes. Continued sequence differentiation via Y inversions has lead to further stratification of the XAR on the X chromosome (not shown), whereas deletions have contributed to the remarkable shrinkage of the Y relative to the X. Recombination between X and Y is restricted to only the distal end of the chromosomes (for simplicity, only pseudoautosomal regionPAR 1 is shown; see text for details). Colour is used to denote autosomal (grey), X‐specific (pink) and Y‐specific (blue) sequence. Shading represents the level of sequence homology between the chromosomes; dark shading indicates high similarity and lighter shading indicates progressive divergence. Black Xs represent regions of recombination between the chromosomes.



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Further Reading

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Kvikstad, Erika M, and Makova, Kateryna D(Sep 2013) Rapid Evolution of Genes on the Human X Chromosome. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020858.pub2]