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Scott Keeney studies where breaks in chromosomes happen during the genetic shuffling step of meiosis. Angelika Amon is interested in how the cells know how to progress from one stage of meiosis to the next.
Today, scientists know that these “threads” are chromosomes containing the cell's genetic material. The dynamic changes visible through a microscope occur as chromosomes bunch together, readying themselves for the precise ballet of meiosis.
From the Greek word for “to make smaller,” meiosis is the divvying up of chromosomes inside cells destined to become eggs and sperm. Through meiosis, each precursor cell divides into four cells with only half the genetic material of most cells in the body. These resulting germ cells are primed to pass on their unique genetic fingerprint to the next generation.
Through their keen observations, scientists in the 1880s and 1890s deduced that germ cells accomplished this halving of chromosome number through two successive divisions, but the mechanism remained a mystery.
“The cytologists who looked at chromosomes figured out that there were two divisions but they didn't even know what chromosomes were yet,” says Nancy Kleckner of Harvard University, one of the first geneticists—along with HHMI investigator Shirleen Roeder—to bring molecular analysis to the study of meiosis in the 1980s.
Kleckner, Roeder, and others have spent the past two decades using modern genetics, biochemistry, cell biology, and structural biology to reveal exciting new details of meiosis. Each researcher sheds light on a different angle of meiosis, with the hope of illuminating all aspects of the complicated process.
Scientists interested in chromosome dynamics and DNA cell cycles had already tackled the tamer cousin of meiosis—the comparatively straightforward copying of chromosomes and division, referred to as mitosis, that happens in most cells. After characterizing the cellular machinery that controls mitosis, these scientists turned their attention to how a cell borrows that machinery for meiosis.
“Meiosis is mitosis with some bells and whistles,” says Scott Keeney, an HHMI investigator at Memorial Sloan-Kettering Cancer Center. Some of the bells and whistles that he and other scientists are making headway in understanding: In meiosis, matching segments of genes are shuffled to make new combinations. Meiosis has not one but two chromosome divisions. And some stages of meiosis go wrong more often with age, which explains the higher incidence of birth defects in the children of older parents.
Photos: Amon: Matt Kalinowski, Keeney: Allan Zepeda / AP ©HHMI