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Making New Species
Researcher studies evolution using mice, apes and Neanderthals
Jeffrey Good, the newest addition to UM’s biology department, might be one of those rare professors who becomes as animated about house mice as he does his more charismatic subjects, the great apes and the Neanderthals.
All three star in his work to understand the evolution of reproduction at the molecular level. Basically, he studies how sex has shaped the breathtaking array of species on earth, including us. Good’s findings are part of recent breakthroughs in how and when species diverge from one another. In the last year, the 33-year-old’s research has appeared in the prestigious journal Science three times and in Nature.
Good came to Montana in January from a two-year National Science Foundation postdoctoral fellowship at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. There, he joined a team reconstructing the genome of Neanderthals under the direction of Svante Pääbo, one of the first scientists to study ancient DNA. Their findings splashed headlines across major newspapers in May: “Signs of Neanderthals Mating With Humans” (The New York Times) and “A Little Neanderthal May Lurk in all of Us” (The Philadelphia Inquirer).
Good studied wild chimps such as this one from Tchimpounga Sanctuary in the Republic of Congo. (Photo courtesy of Michel Halbwax and Anne Fischer)
While significant, that little bit of Neanderthal is a whopping 1 to 4 percent, Good says. Interestingly, people of African descent do not show any Neanderthal DNA. That helps pinpoint where Neanderthals and modern humans intermingled — most likely soon after they radiated north out of Africa (50,000 to 80,000 years ago) but before humans migrated across Asia and Europe, explaining why Neanderthal heredity extends to both of those groups.
While Neanderthals went extinct 30,000 years ago, the results of the new study tell us they live on within many of today’s peoples.
Good also began a massive project at the Max Planck Institute to compare 285 reproductive genes and 100 randomly chosen genes in chimpanzees, bonobos, gorillas and humans. He looks for genes that are evolving rapidly among primates with very different mating behaviors. While studies have revealed strikingly different social systems among primates, his inquiry delves into the underlying genetic basis for passing on fitness.
So how do house mice fit in? For most people, it’s hard to see them as anything but undesirable pests that invade kitchens and elude snap traps. For Good, they’re about the best subject around for clues to one of the great mysteries in life — the formation of a new species. His zest for house mice began in 2002 as a doctoral student in the laboratory of Michael Nachman at the University of Arizona.
“To better understand the evolution of reproductive isolation, house mice from Europe are ideal subjects,” Good says.
By reproductive isolation, he’s referring to two populations of very similar species that cannot produce fertile offspring. In Europe, the native house mouse comes in two varieties — Mus musculus and Mus domesticus (our introduced version from Europe is the species domesticus).
“The two species are not completely reproductively isolated,” Good says. “They are not very different and are still breeding in nature but not completely. We’re focused on that initial phase of species formation when one population has split into two and can’t come back together.”
About a half-million years ago, the mice formed one common population. Geographic isolation most likely caused them to split into three distinct species, with musculus and domesticus dividing Eastern and Western Europe respectively. The third, Mus castaneus, inhabits Southeast Asia.
Only in the past couple of thousand years have the two European species come into contact—scurrying from house to house. You might predict that in this overlap zone the two similar species would mix, yet so far it appears the two kinds are remaining distinct. Some curious genetic element prevents successful mating from producing fertile offspring.
One of the culprits is the X chromosome in males of Mus musculus, a key finding of Good’s research. It took University of Arizona researchers three years and 10 generations of mice to identify the misfiring X chromosome. That’s another reason why house mice are so ideal for study — they multiply quickly.
Good bred the mice to move the X chromosome selectively between the two species. He discovered that moving the X chromosome from musculus to domesticus caused massive sterility in males, but not in females. Transferring the X chromosome the other direction from domesticus to musculus did not cause sterility in either males or females.
The implication, Good explains, is a complex genetic basis for hybrid male sterility during a time that could be linked to the early phases of forming new species. He’s getting closer to pinpointing just where and when something changes to cause one living organism to be distinct from another.
“The genes on the X chromosome of musculus can’t interact properly when placed on the genetic background of domesticus,” he says. “That tells us that something has changed on the Mus musculus X chromosome, but it is not localized to one gene or one location.”
Today in Good’s lab at UM, he continues to pursue the X chromosome puzzle. He’s looking at a process that humans share as well. When males produce sperm in their testes, there’s a crucial step when genes on the X and the Y chromosomes must be inactivated and then reactivated later in development. If that is disrupted, you end up with sterility.
“We’re finding that genes on the X chromosome in the sterile males keep making more copies of themselves when they should be turned off,” Good says.
What Good uncovers about mice could some day apply to people in the quest to understand causes of male sterility in humans. The relevance of his research to people is more obvious in his work with primates and fossil Neanderthals, started at the Max Planck Institute and continuing today at UM.
Good is the lead researcher for the largest population genetic survey of great apes (technically defined as gorillas, chimpanzees, bonobos, orangutans and humans) ever conducted. He and his colleagues at the institute are examining sexual selection that is invisible to us, yet critical to evolution. They’re checking out sperm competition, as well as the evolution of immune responses to disease.
Both female chimpanzees and their smaller relatives, the bonobos, mate with multiple males. For a chimpanzee female, mating with many males plausibly gives some assurance that males will not kill her offspring. In contrast, the bonobos appear to have multiple partners as a peaceful way to mediate conflicts. Yet, at the sperm level, both kinds of primates face similar postmating competition. When females mate with multiple males, which sperm will succeed in fertilizing an egg?
In sharp contrast, massive gorilla males fend off smaller competing males and protect a harem of females. Here, it’s a different arena for sexual selection, similar to bull elk in Montana clashing antlers with other males and guarding cows. The goal is to pass on one dominant male’s genes to a large group of females.
The Max Planck Institute has the advantage of access to genetic samples from wild primates, gathered by veterinarians from sanctuaries in Africa. In turn, the institute supports critical conservation efforts to save the increasingly rare apes. Good explains that samples from zoo animals are not as reliable because of uncertain backgrounds, inbreeding and other issues.
“What we’re looking for are genetic differences within and between species,” he says. “Multiple mating could lead to a suite of processes that drive adaptive evolution at the molecular level. For example, in addition to direct competition between males, sperm from multiple males could also introduce more chances of diseases to the female. So there could be natural selections for reproductive genes involved in immune defense. We’d like to identify genes that evolve rapidly to help us understand which functional aspects of reproduction have been most important during the evolution of different species of great apes.”
Now settled at UM, Good looks forward to applying his genetic evolution pursuits to projects close to home. He will join UM Professor Scott Mills’ search to uncover the genetic basis of seasonal color changes in snowshoe hares, a project relevant to climate change. He also plans to return to the subject of his graduate studies at the University of Idaho, the evolution of ground squirrels and chipmunks.
What about house mice? As more revelations unfold from studying them in Good’s lab, perhaps more people may grow to appreciate the few redeeming values of those pesky intruders.
— By Deborah Richie Oberbillig
|(Above) Assistant Professor Jeffrey Good and one of his research subjects