Researchers map the sperm proteome, laying the groundwork for a wave of new research into the sex cell.

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For all the time we spend talking about sex, you’d think we’d know a little more about it. But scientists understand surprisingly little about half of the species’ contribution to fertilization: sperm. One team of scientists, however, has now substantially advanced that knowledge.

Biologists at the University of Bath in the UK have completely cataloged the proteins in the fruit fly sperm cell, creating the first such inventory for any cell. Their findings have been published in the Nov. 12 online edition of Nature Genetics.

“This is the first sort of directed catalogue of as many proteins that we can identify in one species and in one sperm cell,” said Tim Karr, an evolutionary biologist at the University of Bath and lead author of the study. He added that only 10 or 12 proteins were known prior to this study. “We knew there had to be many, many more. You can’t make a sperm cell with ten proteins; you need hundreds and maybe thousands.”

Sperm are relatively simple cells, consisting of a head, body, and tail. When a sperm cell penetrates an egg cell, it fuses with the egg to form a zygote and, eventually, an embryo. Though scientists have been studying fertilization for hundreds of years, sperm has been overlooked because of its seeming simplicity, in both form and function. 

Sperm cells are, however, critical; not only does sperm have DNA, it also carries RNA and proteins that affect fertilization and embryonic development. About half of the genes in the fruit fly sperm proteome—the catalogue of all proteins in the cell—have comparable versions in humans, making the findings of the new study useful for comparative studies on how sperm cells evolved, as well as for studies on male infertility.

“The new sets of proteins that we’ve identified are, by definition, all very interesting,” Karr said.  “To know how sperm works, you have to first know what’s inside sperm.”

In their experiments, the researchers isolated sperm from Drosophila melanogaster, the common fruit fly, and “chopped” up the proteins into smaller pieces. Subsequent analysis by mass spectrometry, a technique used by chemists to analyze the composition of small molecules, revealed what proteins were present, allowing researchers to determine which genes had been expressed.

They identified 381 proteins in the sperm proteome, a 50-fold increase in the number previously identified. The data revealed that the sperm proteome could be divided into seven broad functional categories. Not unexpectedly, they found that 21 percent of proteins were involved in energetics and metabolism, and nine percent were cytoskeletal proteins. But proteins whose functions were unknown made up a whopping 31 percent of those identified.

“Believe it or not, that’s where we’re at; that’s the level of our ignorance,” Karr said.

Identifying the proteins present in sperm and determining their functions could have far-reaching implications for researching and treating male infertility.

“This paper is a significant advance in studies on sperm and evolution in reproductive biology,” said Diane Chu, a geneticist at San Francisco State University who uses the roundworm to study genes involved in male infertility. Comparative genetic studies will help isolate which proteins might be implicated in male infertility, Chu said, helping to identify male contraceptive targets and possible treatments.

“Proteins that we identify could play roles in compacting and protecting the DNA from damage, keeping sperm motile and active, and making sure that sperm can recognize and fertilize the egg,” she said, adding that decreased DNA compaction in the sperm cell is one cause of male infertility in the roundworm.

Gas8, a fruit fly gene that has a closely related equivalent in humans, has been shown to be involved in sperm motility. Mutations in this gene have been implicated in infertility.

“By studying the function of Gas8, we may be able to learn what Gas8 is doing in Drosophila sperm and infer the function of what’s going wrong in the mammal and human,” Karr said. “We’re still trying to work out a lot of the details of how fertilization works at the molecular level.”

Karr’s study will also help to elucidate some of the mechanisms behind the evolution of sperm and, subsequently, sexual selection of reproductive traits.

“With the proteome known…evolutionary geneticists can now look at how rapidly the sperm genome is evolving,” said Steve Dorus, coauthor of the study and an evolutionary geneticist at the University of Bath who studies sexual selection. “The success of an organism is measured by its reproductive fitness. Any sort of biological trait that is associated with the most critical measure of the organism’s success would be under intense selective pressures.”

Instead of studying individual proteins, evolutionary biologists can examine the entire proteome in a more systematic way. “It’s a very powerful data set,” Dorus said. “It gives us a more global view of how selection impacts reproductive genetics. For the first time we can look at evolution of genes in sperm.”

Originally published November 29, 2006


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