The sex chromosomes – Y is there a Y and the great X-scape

Throughout evolution many mechanisms to determine sex have arisen. Whilst in many species sex is determined genetically, environmental factors such as temperature or even social variables such as size can influence the fate of an organism’s sex. Other species change sex throughout their lifetime. In humans, sex is determined by the sex chromosomes present in the genome; females have two X chromosomes (XX) whilst males have an X and a Y (XY). The two chromosomes have taken different evolutionary trajectories resulting in differing genomic compositions. Recent studies have highlighted lineage-specific and general evolutionary mechanisms for the Y chromosome and have questioned our understanding of X chromosome inactivation.

x and y.png
Cartoon X chromosome, left and Y chromosome right


An autosome origin

Along time ago X and Y chromosomes began life as autosomes – these are chromosomes not involved in determining sex that come in pairs, one originating from each parent. The X chromosome still closely resembles an autosome but the Y has undergone dramatic modification. Understanding the Y chromosome, however, has previously been challenging due to its highly repetitive structure, though this is diminishing with improved sequencing techniques.

A recent large-scale sequence comparison across several Dipteran (flies) families of Y chromosomes have highlighted convergent evolutionary patterns (1). By analysing ‘young’, degenerating Y chromosomes, an initial phase of formation involves retention of testis-expressed genes throughout a period of massive gene loss. Degeneration is a consequence of the lack of recombination between two Y chromosomes since the Y chromosome travels through generations alone. A later stage involves the gain of male-specific function genes from other autosomes.

Mammals vs. flies

Unlike flies that contain few male-specific function gene derived from other autosomes, mammalian Y chromosomes still retain ancestral genes. It is believed this is a consequence of the differing dosage compensation mechanisms used by the lineages.

Dosage compensation allows expression from the X chromosome to match that of the autosomes which have two copies, one originating from each parent. The consequences of having unbalanced expression from autosomes and sex chromosomes are most evident from people with Klinefelter or Turner syndrome where they have genotypes of XXY or XO respectively, commonly leading to infertility and various physical abnormalities*.

Flies tackle this by a two-fold up-regulation of the genes on the single male X chromosome to match the autosomes. In mammals, to deal with dosage levels one of the X chromosomes is inactivated at random. The remaining active X chromosome has increased expression as does the single X in males.

*For more info on dosage compensation see the Wikipedia page (

The great X-scape

Due to the random nature of X inactivation in mammals, females end up as a patchwork of cells containing either the maternal or paternal X chromosomes. However, it is becoming ever more apparent that X inactivation is incomplete. In fact, it was recently shown that a quarter of genes on the inactivated X were still being expressed (2) – 15% genes constitutively escape the inactivation whilst other genes vary per individual and tissue-type.

Of these genes many are involved in the structure of chromosomal DNA and thus can have genome-wide implications. Earlier this year, it was found that six of the X-escape genes were potential tumour suppressors which may provide the explanation for why men are more cancer prone with twice the risk of dying from malignant diseases (3). With these discoveries only in their infancy it will be interesting to see what future studies can reveal about the consequences of the sex chromosomes inherited.

Further Reading

(1)  S.Mahajan. Convergent evolution of Y chromosome gene content in flies Nature Communications 8, 785 (2017)

(2)  B.Balaton. Derivation of consensus inactivation status for X-linked genes from genome-wide studies Biology of sex differences (2015)

(3)  A.Dunford. Tumor-suppressor genes that escape from X inactivation contribute to cancer sex bias Nature Genetics 49, 10-16 (2017)


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