Y Chromosome I: A Brief History

This first post in my Y chromosome series will briefly discuss the history of Y chromosome research. The general outline is derived from the introduction of Skaletsky et al. (2003). I will hopefully fill in the numerous missing parts as the series continues. Anyway…

As the 1920s began, the existence of the Y chromosome was still being debated. The X chromosome was well-established by then, but it seems biologists believed mammals had an X-0 system – the X was all there was. In 1921, Theophilus Painter (sweet name!) published a very short article claiming he had found the Y in humans and other primates, partly establishing the X-Y system as the most common sex chromosome system in mammals. He would later determine the correct number of human chromosomes – 46.

Afterward, geneticists claimed they had discovered up to 17 Y-linked traits – pedigrees they had found were best explained by genes being located on the Y chromosome rather than the X or the autosomes. Examples include webbed toes, hairy ears, bent fingers and other conditions only a doctor would know. However, in 1957 Curt Stern refuted all of these claims because the pedigrees actually contradicted the geneticists’ claims, not enough information was given by the pedigree (such as the condition of females in the family), or the sample was just too small – one pedigree which seemed to show a Y-linked trait could be explained by chance instead, especially when the condition was shown to be autosomal in hundreds of other pedigrees.  Y-linked traits could exist but the evidence was just not there yet. The Y’s role in sex determination was still unknown.

A decade later Susumo Ohno published a monograph titled Sex Chromosomes and Sex-linked Genes but because I cannot currently gain access to it, I instead read his 1969 annual review which unfortunately focuses on the X chromosome (and dosage compensation especially). That’s something I will blog about later.

Figure 1: The centromere locations in the human karyotype (showed by the horizontal black lines). A similar figure for the mouse genome could not be found. Source: Wikipedia (Human genome).

The reason I want Ohno’s work is because his paper is cited in almost every sex chromosome paper I read due to Ohno’s Law: the sex chromosomes in mammals are shared by common descent, evolved from a pair of autosomes, and were protected from the significant translocations and duplications that occurred on other chromosomes.

At the time an unchanging X may have been provocative due to the diversity in chromosome number and configuration in mammals. As examples, the white rhinoceros has 82 chromosomes while humans have 46; the mouse’s chromosomes are all acrocentric (centromere at the ends of chromosomes) (according to Ohno) whereas humans have a variety of metacentric (in the middle) and acrocentric chromosomes (Firgure 1). So despite this diversity, Ohno thought the X had mostly gone unchanged.

As evidence he cited the measurements of chromosome size – across humans, cats, dogs, and cattle the X was nearly the same size, but due to the relatively primitive instruments at the time I do not know if this evidence has withstood superior measurements. I’m sure it will pop up later. However, the law (why call it a law in the first place?)’s predictions of common descent for the X (and Y) from autosomes have consistently been confirmed since.

However, even in 1969, the role of the Y was still undetermined. Did the presence of two X chromosomes determine sex or did the presence of the Y? Ohno unfortunately does not discuss the Y chromosome in detail but according to Skaletsky et al. (2003), his work established the Y as barren of genes and function. Once SRY, the sex determining gene was discovered the Y would gain role in function, but it seems it wasn’t really until the 1990s/2000s that the Y was proven to also be architecturally and evolutionarily interesting. That is where our story will continue next time.

________________________

Ohno, S. (1969). Evolution of Sex Chromosomes in Mammals Annual Review of Genetics, 3 (1), 495-524 DOI: 10.1146/annurev.ge.03.120169.002431

Painter, T. (1921). THE Y-CHROMOSOME IN MAMMALS Science, 53 (1378), 503-504 DOI: 10.1126/science.53.1378.503

Skaletsky, H., Kuroda-Kawaguchi, T., Minx, P., Cordum, H., Hillier, L., Brown, L., Repping, S., Pyntikova, T., Ali, J., Bieri, T., Chinwalla, A., Delehaunty, A., Delehaunty, K., Du, H., Fewell, G., Fulton, L., Fulton, R., Graves, T., Hou, S., Latrielle, P., Leonard, S., Mardis, E., Maupin, R., McPherson, J., Miner, T., Nash, W., Nguyen, C., Ozersky, P., Pepin, K., Rock, S., Rohlfing, T., Scott, K., Schultz, B., Strong, C., Tin-Wollam, A., Yang, S., Waterston, R., Wilson, R., Rozen, S., & Page, D. (2003). The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes Nature, 423 (6942), 825-837 DOI: 10.1038/nature01722

Stern C (1957). The problem of complete Y-linkage in man. American journal of human genetics, 9 (3), 147-66 PMID: 13469791