Profile of Nancy A. Moran

“I've always had a research theme of biological complexity and how it came to be.”

“I always liked insects,” says Nancy A. Moran, Regent's Professor of Ecology and Evolutionary Biology at the University of Arizona (Tucson, AZ). “As a little kid, I was known as the girl who collected insects and had them in jars and things like that.” Years later, this youthful bug collector has become a renowned entomologist whose work crosses over into multiple disciplines, including microbiology, ecology, and molecular evolution. Moran's research primarily focuses on the ecology and evolution of aphids and, since 1990, has especially focused on the interaction and coevolution of these small insects and the symbiotic bacteria that live inside of them.

“The whole evolution of insects has been in tandem with these bacteria,” Moran says. “We would not see insects feeding on plant sap if it weren't for symbiosis.” Elected to the National Academy of Sciences in 2004, Moran reveals another level in this symbiont-host relationship in her Inaugural Article in this issue of PNAS (1). She shows that in Hamiltonella defensa, a bacterium that helps protect aphids against parasitic wasps, the toxin genes that provide defense are embedded within phage genomes. Because the phages have variable genomes, the bacteria have evolved multiple isolates containing different toxins. “The phages are a very dynamic part of the symbiont genome,” she says, “and form an integral component of the aphid-bacterium mutualism.”

Movies and Books

Despite her early career as a budding entomologist, when she was young, Moran never envisioned becoming a scientist. Born and raised in Dallas, TX, no one in her family was an academic, and she encountered no pressures or expectations to pursue science. In fact, she did not find her private school biology class particularly interesting. Moran actually grew up surrounded more by science fiction than science fact—her father, Robert Moran, ran a local drive-in movie theater, and Moran and her seven siblings spent a lot of time helping out with the family business.

Moran began her undergraduate studies at the University of Texas (Austin, TX) in 1972. She enrolled in an honors program known as Plan II, which allowed students to create their own flexible academic plan. This option was ideal for Moran, who found almost every study field interesting. “There were so many interesting subjects that I didn't even settle down in one particular direction for a while,” she says. “I started out as an art major, and then I switched over to a philosophy major.” Then, one semester, she enrolled in an introductory biology course, initially just to complete an elective. “They used the famous Keeton textbook [Biological Science], which I thought was really good,” she recalls. “Basically just from reading that book as much as anything else—I don't even really remember the lectures—I became interested in biology and took several more classes.”

During her senior year at college, when she undertook an honors project to complete her Plan II requirements, Moran decided to try something in biology. “I happened to take a class on animal behavior. The TA was Nancy Burley, who would later become well established in bird behavior, and I did a project with her on mate choice in pigeons” (2). The project solidified an interest in evolution and behavior for Moran and gave her a taste of what independent research could be like. Thus, she decided to apply to graduate school. “It was all sort of last minute, so I wasn't at all in the know about anything,” she says. “I asked the people around me for advice on where to apply, and they named some places, and I eventually ended up at the University of Michigan (Ann Arbor, MI).” She graduated from the University of Texas with a bachelor's degree in biology in 1976.

When Moran arrived at Michigan that year for graduate school, her exact research goals were up in the air. “At that time, a lot of people were interested in the evolution of sex and genetic recombination,” she says. “Why have males and females, and not just reproduce by parthenogenesis and have all females?” One of her advisors, William Hamilton, had proposed that sexual reproduction was important to create genetic diversity to stay one step ahead of coevolving natural enemies, especially parasites and pathogens. “I became interested in that idea and began looking at it in aphids,” she says, “which are very useful since they are parthogenetic for part of their life cycle” (3).

After receiving her Ph.D. in zoology in 1982, Moran spent the next several years studying evolutionary ecology in aphids. “It was less than completely satisfying in a lot of ways,” she admits. “At that time you were so far from the actual genetic basis of the variation you were looking at, so you had no handle as to which genes were actually causing the variation. Everything was like a black box.” Moran carried out this challenging research in postdoctoral studies at Northern Arizona University (Flagstaff, AZ), followed by a faculty appointment at the University of Arizona in 1986, where she has remained since.

Old Association and a New Collaborator

Shortly after arriving at Arizona, Moran began to work on a side project examining a local aphid species, Melaphis rhois. “This aphid has a very peculiar life cycle, just extremely weird,” she explains. “For part of its life cycle it forms this complex gall, or plant tissue deformation, on a species of sumac. Then, in other part of the cycle, it feeds on mosses. So during the course of its life, it has to migrate from one plant to the next.” Initially, Moran thought this behavior could be a complex adaptation to changing seasons, but M. rhois was found to have sister aphid species living in China and Japan. “The only way you could explain this distribution is that it's very, very ancient,” she says. In fact, the life cycle dated back at least 50 million years, at a time when sumac was dispersed across the Bering land bridge and was present in both the Asian and North American continents, making it the oldest known continuous association between an insect and a plant (4).

“Anyway, I didn't think this paper was a big deal, and I was going to publish it in some tiny little journal, if at all,” she explains. But one of Moran's colleagues suggested that she send her paper to the journal Science, because the ancient aphid-plant association seemed like an interesting discovery. “And so I did, and they published it,” she says, “and the good thing about that was that Paul Baumann at [University of California] Davis, a well known molecular geneticist who was interested in bacterial diversity, saw the paper and called me up. He said he would like to work with someone who knew something about aphids because he was interested in the bacteria that live in [them].” So, in 1990, Moran and Baumann began what would become a continuous collaboration spanning 15 years and numerous grant proposals, getting to the heart of the mutualistic relationship between aphids and their tiny bacterial guests.

Their first collaborative project involved reconstructing the evolutionary history of the primary aphid symbiont, Buchnera aphidicola. Moran and Baumann compared the 16S rRNA sequences from 11 different aphid species “back when sequencing one 16S was considered an accomplishment,” says Moran, and found an ancestral relationship between insect and bacteria (5). “The associations with these bacteria go all the way back to the origins of those groups of animals,” she says, “and the two have coevolved such that basically when the insects speciate and diversify, you get this parallel diversification of the bacteria.” Moran and Baumann next demonstrated that this symbiotic coevolution was not limited to aphids but was present among other insect species (6, 7). “As we were doing this, I sort of gradually became interested in bacterial genome evolution,” she says, “especially the back-and-forth between the genome evolution of the symbiont and the ecology of the host and how that affects the symbiont. And a lot of interesting patterns show up in these symbionts.”

One of the most compelling characteristics of these symbionts is their small genome size. “Buchnera only have 600 genes, compared to about 4,000 or 5,000 for E. coli,” says Moran. “This is a recurring pattern in the genomes of both bacterial symbionts and pathogens, but why do they get so small?” Two reasons were the loss of genes that were no longer needed in the host environment and the lack of opportunity for these symbionts to pick up additional genes through horizontal transfer. By comparing the Buchnera with some free-living bacteria, Moran identified a third reason: she observed that Buchnera genes tended to accumulate more nonsynonomous mutations and amino acids with codon families rich in A + T base pairs, which indicated that the symbionts underwent accelerated evolution compared with related free-living bacteria (8). Therefore, these symbionts accumulated mutations that eventually knock certain genes out. “So while part of the reduction is due to adaptation, a lot of it just reflects genetic drift,” she explains.“ It's just a consequence of long-term evolution in a restricted environment with small population sizes.”

Opportunity to Study Opportunists

Moran's groundbreaking work on bacterial symbiosis would earn her the honor of receiving one of the annual MacArthur “genius” grants in 1997. Although the award itself was exciting, the monetary award that came with it was also a blessing. “I was able to use that to pay some of my salary so I didn't have to take on a full teaching load for a year or two,” she says, “and that gave me more free time for my research and to have more time with my child.” That same year, Moran attended the Gordon Conference in Microbial Population Biology and met Howard Ochman, a molecular geneticist at the University of Rochester (Rochester, NY). Although this meeting would prove most significant because Moran and Ochman would later marry, this encounter also shifted the course of Moran's research.

Moran was curious about the secondary, or facultative, bacterial symbionts often present in insects. Unlike primary symbionts, which provide essential nutrients, these secondary symbionts were both horizontally and vertically transmitted, were not essential for host survival, and conferred no known benefits. These symbionts could, however, prove to be valuable research models because they represented a more recent stage of a host-symbiont relationship. “These symbionts resemble bacterial pathogens in a lot of ways,” says Moran. “I mean, from the host point of view, the outcome can be different, but these bacteria have to invade a host, get into a cell, and then influence the host's biology, even if they do it to help the host.”

Of course, how these facultative bacteria helped the host was largely unknown, but together with Martha Hunter and graduate student Kerry Oliver, Moran demonstrated that in aphids, secondary symbionts helped confer resistance to attacks by parasitic wasps, and that different isolates of bacteria conferred varying degrees of protection (9, 10). Unfortunately, another key difference between primary and secondary symbionts was that secondary symbionts were not localized within specialized host organs and were present in very low amounts. Therefore, characterizing the genomic content of these symbionts, as well as the mechanisms of how they confer resistance, was extremely difficult. Ochman, however, happened to be investigating a method for amplifying whole-genome DNA from low-copy templates and was looking for potential applications. In a previous collaboration with Ochman and Colin Dale using directed PCR, Moran had shown that a facultative symbiont within grain weevils expressed homologs of the inv/spa genes, components of a secretion system used by bacterial pathogens like Salmonella to invade cells (11). Because Moran wanted to know what other interesting genes might be present within symbionts, she and Ochman decided that secondary symbionts would make a good test case for his DNA amplification technique.

In her PNAS Inaugural Article (1), Moran utilized Ochman's method and found that facultative symbionts of aphids do indeed have additional genes associated with pathogenesis, including toxin genes. “And when you look at different bacterial isolates,” she says, “they have different toxins. Some have homologs of the shiga toxin, others have cytolethal distending factor, and some have other unknown genes.” Moran suggests that these toxins are targeted against the eggs laid by parasitic wasps, and the degree of resistance varies due to the differing toxic mechanisms: “Depending on the local ecology, selection might favor one type over another type.”

Moran hopes to continue conducting further research on these opportunistic symbionts in both aphids and other insect species. “Some insect groups have very elaborate systems of symbiosis where they can have up to six different bacterial symbionts at once in the same insect, and it seems that in these cases the different symbionts are actually dependent on each other,” she says. “You have reductions in the metabolic capabilities in one symbiont because it becomes dependent on another symbiont, and you can end up having a set of organisms, all of which have to live together. So it adds a layer of complexity to this community.”

Importance of Randomness

“I've always had a research theme of biological complexity and how it came to be,” says Moran. Recently, Moran has continued to increase the complexity of her work by venturing away from insect symbionts and increasing her focus on bacterial evolution as a whole, another influence partially attributed to Ochman. Along with Vincent Daubin, Moran and Ochman recently picked their way through the morass of lateral gene transfers that occur between different bacterial species and built a phylogenetic tree for bacteria in the Escherichia coli family, a feat many researchers thought unattainable (12).

Having doubts about the importance of natural selection as the sole force important in evolution could be another theme, and, to that end, Moran has lately been intent on educating biologists on the roles of genetic drift and historical happenstance in evolution. “It's always made me kind of uneasy that you would just start with the assumption that organisms are well adapted and perfectly suited to their environment,” she says, “so I always give little sections on genetic drift when I talk about my work. It's tempting just to skip over it, because outside of population geneticists, people don't think about it much and don't really want to think about it.”

But she thinks an improved understanding of genetic drift and random chance could help prevent the misunderstandings surrounding evolution. “I think part of the problem in teaching evolution is that people are used to thinking of everything as adapted while ignoring chance events,” she says, adding that molecular biology is often taught like so-called intelligent design. “It's like this binds here, that binds there, it's all complicated and yet somehow it all works,” she says. “If more people thought about mutation, genetic drift, and population processes as important aspects of evolution, I think the understanding of evolution would be better.”

Figure 1.

Nancy A. Moran

Figure 2.

Moran collecting psyllid galls, containing bacterial symbionts, on the University of Arizona campus.