A sex-linked supergene controls sperm morphology and swimming speed in a songbird

Try to imagine sperm competing to fertilise an egg - and I accept probably not everybody thinks about this! You might picture a cartoon where the fastest sperm have the longest tails, beating furiously to ensure they win the race. In reality, we know remarkably little about why some males have longer and faster sperm than other males.

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For more than two decades, my colleague Tim Birkhead has been using zebra finches as a model system for studying sperm traits. His work has shown that sperm shape and speed are heritable; fathers with long, fast sperm have sons with long, fast sperm. We also know that the genes that make sperm longer also make them faster. What we didn’t know at the start of this study is what those genes were.

A male zebra finch (photo Tim Birkhead)

A few years ago we were fortunate enough to be funded by the Biotechnology and Biological Sciences Research Council (BBSRC) to find the genes that cause variation in zebra finch sperm. By then, we had also used selective breeding to create lines of males with long or short sperm. In just 4 generations, there was almost a 20% difference in length between the two lines - a bit like comparing people who differ in height by a foot. We had also played a big role in developing genomics tools for zebra finches. Using the full gamut of genomics techniques our postdoc, Kang-Wook Kim set to work. We found the genes with the greatest expression differences in the testes of males from the two lines. We also performed gene mapping studies, similar to those used in human medical studies, to find which genes and chromosomes were associated with sperm shape and speed. Finally, we identified the parts of the genome that had caused the response to our selective breeding.

Our expectation was that we would find genes that explained some, but perhaps not that much, of the differences in sperm between males. These genes would probably be scattered across the zebra finch genome. Perhaps, we would be able to say something about the function of these genes. They might even be of interest to the medical and veterinary community.

What we actually found was rather different and much more exciting. Like humans, birds have sex chromosomes, only in birds they are called Z and W; males have two Z chromosomes (ZZ) and females are ZW. The Z chromosome is only about 7% of the zebra finch genome, yet it was almost entirely responsible for the genetic differences in sperm. At first this was a surprise, until we realised that in some zebra finches the Z chromosome is ‘flipped around’ resulting in what geneticists call an inversion polymorphism or more informally a ‘supergene’. The different orientations (unimaginatively named A, B and C) of the Z chromosome have been evolving independently of one another for very many generations. Our results show that genes that affect sperm have evolved on each of them, and because males have two copies of the Z chromosome, those males with different versions of the supergene (e.g. AB males) have better sperm than males with two identical copies (e.g. AA males). This is called heterozygote advantage, and because males with alternative copies (heterozygotes) have the best sperm, all of the different versions of the supergene are maintained at an equilibrium.

Stained sperm of zebra finch males with different Z chromosome supergene karyotypes. AA males have short midpieces (horizontal line) and long tails. BB and BC males are the opposite. AB and AC males have relatively long midpieces and tails, and have the fastest, most competitive sperm.

We worked with Simon Griffith and colleagues at Macquarie University, to show that the effects were repeatable in wild Australian zebra finches. Meanwhile, and completely independently, a group led by Wolfgang Forstmeier at the Max Plank Institute for Ornithology in Germany arrived at essentially identical conclusions, but from a very different starting point. They were interested in the Z chromosome supergene, and what enabled it to persist in nature. After ruling out effects on other traits such as body size and shape, they identified the same pattern we saw on sperm traits. Thus, the overall findings have not only been replicated in different zebra finch populations, but also by different research groups taking conceptually different approaches; it’s rare to see this level of replication of new research findings.

Our paper neatly demonstrates several evolutionary predictions that have been hard to support empirically. Supergenes were first proposed to be important in the 1930s, evidence of heterozygote advantage has largely relied on a single example from the 1950s, and the Z chromosome was first predicted to be important for male traits in birds in the 1980s.

@jon_slate; j.slate@sheffield.ac.uk

The paper in Nature Ecology & Evolution is here: http://go.nature.com/2tU43VZ

Jon Slate

Professor, University of Sheffield