Taking a DNA molecule into the vicinity of a homologous target gene by a DNA aptamer provides a many-fold enhancement of gene correction frequency at that genetic locus. Aptamer-guided gene targeting, or AGT, is a novel approach for genetic engineering developed by Patrick Ruff in Francesca Storici’s group.
Gene targeting is a genetic technique to modify an endogenous DNA sequence at will, by changing a mutant DNA sequence into a wild-type copy or vice versa in its genomic location via homologous recombination. Gene targeting is therefore a fundamental process not only for functional analysis of genes, proteins, and complex biological systems, but potentially also in molecular therapy for the prevention and cure of human genetic diseases originating from specific DNA alterations. However, editing of genetic information is a challenging task. The goal of gene correction goes far beyond the process of making a desired change in a chosen target gene in the most efficient way. It is essential that the product of the modified gene should then be functional, the DNA correction stable, and the engineering process accurate and restrained to the target in order to minimize unwanted DNA, cellular, and/or tissue damage.
In the most recent years a lot of progress has been made in activating cellular DNA repair and recombination machinery at the target sites for gene correction, mainly via the specific induction of DNA double-strand breaks (DSBs) at these sites. However, there has been much less focus on the other essential component for gene targeting: the donor DNA necessary to make the desired modification. To address the problem of donor DNA availability, Patrick Ruff, fresh PhD recipient in the lab of Francesca Storici from the School of Biology at Georgia Tech, developed a novel gene targeting approach, aptamer-guided gene targeting (AGT), in which he bound the homing endonuclease I-SceI by a DNA aptamer fused to the donor DNA of choice, to target the donor DNA to a desired genetic locus located next to an I-SceI cut site. DNA aptamers, which mimic antibodies, are sequences of DNA that are able to bind to a specific target with high affinity because of their unique secondary structure. Using a variant of capillary electrophoresis systematic evolution of ligands by exponential enrichment (CE-SELEX) called “Non-SELEX”, Patrick obtained a DNA aptamer for the I-SceI endonuclease, and with the assistance of Storici lab graduate students Kyung Duk Koh and Havva Keskin, and the research scientist Rekha Pai, found that the AGT approach increases the efficiency of gene targeting by guiding an exogenous donor DNA into the vicinity of the site targeted for genetic modification. Dr. Storici said: "by utilizing DNA oligodeoxyribonucleotides that contained the I-SceI aptamer sequence as well as homology to repair the I-SceI DSB and correct a target gene, we were able to increase gene targeting frequencies up to 32-fold over a non-binding control in yeast and up to 16-fold over a non-binding control in human cells".
This study shows that DNA aptamers can be exploited to increase donor DNA availability, and thus promote the transfer of genetic information from a donor DNA molecule to a desired genetic locus. The AGT strategy offers a novel way to increase gene targeting efficiency, represents the first investigation to use aptamers in the context of gene correction, and provides a new direction to the field of genetic engineering.
The study is just published as an article in the journal Nucleic Acids Res (Wednesday February 5, 2014):
Ruff, P., Koh K.D., Keskin H., Pai R.B. and Storici, F. Aptamer-guided gene targeting in yeast and human cells, Nucleic Acids Res, Feb 5 2014 doi:10.1093/nar/gku101 http://nar.oxfordjournals.org/cgi/reprint/gku101?
This project was supported by the Georgia Tech Fund for Innovation in Research and Education (GTFIRE-021763), the NIH grant (R21EB9228), and the Georgia Cancer Coalition grant (award R9028).
Exploiting the use of DNA single- and double-strand breaking forms of the I-SceI endonuclease to stimulate homologous recombination and gene targeting in budding yeast and in human cells, the research of Samantha S. Katz in Francesca Storici’ lab provides new mechanistic insights into the process of nick-induced DNA recombination and on the function of nicking enzymes in genetic engineering.
Enzymes generating a site-specific double-strand break (DSB) in DNA, including homing endonucleases, such as I-SceI, are widely utilized to promote strand exchange between homologous sequences for purposes of characterizing mechanisms of DNA recombination and repair, and to facilitate targeted gene correction in many cellular systems from bacteria to human cells. However, in the most recent years, enzymes capable of making single-strand breaks (SSBs), nickases, have attracted a lot of attention. While a DSB can efficiently stimulate recombination, the competing non-homologous end-joining pathway for DSB repair is often favored, especially in human cells, and poses a major safety problem for gene targeting strategies, in particular for gene therapy applications, because it frequently leads to in/dels or chromosomal rearrangements. Recent work has shown that an SSB not only facilitates gene targeting, but importantly also leads to less off-site targeting damage than a DSB.
Despite the relevance of nicking enzymes, there are only very few available nicking systems, and still a lot remains to be understood about how a nick stimulates recombination and gene targeting in cells. The work conducted by Samantha S. Katz, recent PhD recipient in Francesca Storici lab at the School of Biology of Georgia Tech, in collaboration with Dr. Frederick Gimble from Purdue University, pioneers the in vivo function of the first available I-SceI nicking variant (K223I I-SceI). The team demonstrates that K223I I-SceI nickase efficiently stimulates gene correction in both yeast and human cells, and that such stimulation can occur even at loci 10 kb distant from the break site. Moreover, said Dr. Storici: <<we prove that the K223I I-SceI nickase stimulates recombination via a mechanism that is different from that by which the wild-type I-SceI double-strand nuclease works>>. The authors propose two models for nick-induce gene correction, either by simple unwinding of the broken strand at the nick site, or as a consequence of replication fork collapse and strand resection.
This study provides robust support to the fact that SSB-driven gene editing is a valuable mechanism for applications in molecular biology and biotechnology. The study is just published as an article in the journal PLoS One (Tuesday February 18, 2014):
Katz, S. S., Gimble, F. S. and Storici, F. To nick or not to nick: comparison of I-SceI single- and double-strand break-induced recombination in yeast and human cells
PLoS One, Vol 9, Issue 2, e88840, 2014 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0088840
This project was supported by the Georgia Cancer Coalition grant (award R9028), the National Science Foundation grant MCB-1021763, and the Graduate Assistance in Areas of National Need (GAANN) fellowship.
If a driver is traveling to New York City, I-95 might be their route of choice. But they could also take I-78, I-87 or any number of alternate routes. Most cancers begin similarly, with many possible routes to the same disease. A new study found evidence that assessing the route to cancer on a case-by-case basis might make more sense than basing a patient’s cancer treatment on commonly disrupted genes and pathways.
The study found little or no overlap in the most prominent genetic malfunction associated with each individual patient’s disease compared to malfunctions shared among the group of cancer patients as a whole.
“This paper argues for the importance of personalized medicine, where we treat each person by looking for the etiology of the disease in patients individually,” said John McDonald, a professor in the School of Biology at the Georgia Institute of Technology in Atlanta. “The findings have ramifications on how we might best optimize cancer treatments as we enter the era of targeted gene therapy.”
The research was published February 11 online in the journal PANCREAS and was funded by the Georgia Tech Foundation and the St. Joseph’s Mercy Foundation.
In the study, researchers collected cancer and normal tissue samples from four patients with pancreatic cancer and also analyzed data from eight other pancreatic cancer patients that had been previously reported in the scientific literature by a separate research group.
McDonald’s team compiled a list of the most aberrantly expressed genes in the cancer tissues isolated from these patients relative to adjacent normal pancreatic tissue.
The study found that collectively 287 genes displayed significant differences in expression in the cancers vs normal tissues. Twenty-two cellular pathways were enriched in cancer samples, with more than half related to the body’s immune response. The researchers ran statistical analyses to determine if the genes most significantly abnormally expressed on an individual patient basis were the same as those identified as most abnormally expressed across the entire group of patients.
The researchers found that the molecular profile of each individual cancer patient was unique in terms of the most significantly disrupted genes and pathways.
“If you’re dealing with a disease like cancer that can be arrived at by multiple pathways, it makes sense that you’re not going to find that each patient has taken the same path,” McDonald said.
Although the researchers found that some genes that were commonly disrupted in all or most of the patients examined, these genes were not among the most significantly disrupted in any individual patient.
“By and large, there appears to be a lot of individuality in terms of the molecular basis of pancreatic cancer,” said McDonald, who also serves as the director of the Integrated Cancer Research Center and as the chief scientific officer of the Ovarian Cancer Institute.
Though the study is small, it raises questions about the validity of pinpointing the most important gene or pathway underlying a disease by pooling data from multiple patients, McDonald said. He favors individual profiling as the preferred method for initiating treatment.
The cost of a molecular profiling analysis to transcribe the DNA sequences of exons — the parts of the genome that carry instructions for proteins — is about $2,000 (exons account for about two percent of a cell’s total DNA). That’s about half the cost of this analysis five years ago, McDonald said, and a $1,000 molecular profiling analysis might not be far off.
“As costs continue to come down, personalized molecular profiling will be carried out on more cancer patients,” McDonald said.
Yet cost isn’t the only limiting factor, McDonald said. Scientists and doctors have to shift their paradigm on how they use molecular profiling to treat cancer.
“Are you going to believe what you see for one patient or are you going to say, ‘I can’t interpret that data until I group it together with 100 other patients and find what’s in common among them,’” McDonald said. “For any given individual patient there may be mutant genes or aberrant expression patterns that are vitally important for that person’s cancer that aren’t present in other patients’ cancers.”
Future work in McDonald’s lab will see if this pattern of individuality is repeated in larger studies and in patients with different cancers. The group is currently working on a genomic profiling analysis of patients with ovarian and lung cancers.
“If there are multiple paths, then maybe individual patients are getting cancer from alternative routes,” McDonald said. “If that’s the case, we should do personalized profiling on each patient before we make judgments on the treatment for that patient.”
Loukia Lili, of Georgia Tech’s Integrated Cancer Research Center, School of Biology, and Parker H. Petit Institute of Bioengineering and Biosciences, was the study’s first author. Co-authors included Lilya Matyunina and DeEtte Walker of Georgia Tech, and George Daneker, MD, of the Cancer Treatment Centers of America SE Regional Facility in Newnan, Ga.
This research is supported by the Georgia Tech Foundation and the St. Joseph’s Mercy Foundation. Any conclusions or opinions are those of the authors and do not necessarily represent the official views of the sponsoring agencies.
CITATION: Loukia N. Lili, et al., “Evidence for the Importance of Personalized Molecular Profiling in Pancreatic Cancer,” (PANCREAS, February 2014). (http://dx.doi.org/10.1097/MPA.0000000000000020).
Georgia Institute of Technology
177 North Avenue
Atlanta, Georgia 30332-0181 USA
Writer: Brett Israel
Jeffrey Skolnick, Ph.D., Mary and Maisie Gibson Chair and Georgia Research Alliance Eminent Scholar in Computational Systems Biology at Georgia Tech, will receive the Southeastern Universities Research Association’s (SURA) 2014 Distinguished Scientist Award. The award is given annually to a scientist whose extraordinary work fulfills the society’s mission of “fostering excellence in scientific research.”
Skolnick, who also serves as Director of the Integrative BioSystems Institute, will be presented the award and its $10,000 honorarium on March 18, 2014 at the SURA Board of Trustees meeting at the University of West Virginia at the SURA’s spring board of trustee’s meeting.
“Jeff is extremely deserving of this award as he is one of the outstanding thought leaders in the field and has been called ‘visionary’ and ‘an out of the box thinker’ by many colleagues,” stated Mark Hay, Ph.D., professor and Harry and Linda Teasley Chair in Environmental Biology in the School of Biology at Georgia Tech. “Not only has his research provided unique and fundamental insights into the behavior of biological systems, he has developed several of the best algorithms for virtual ligand screening and for predicting protein structure-function relationships.”
Skolnick is the author or co-author of over 350 journal articles in the fields of systems and computational biology and his cutting edge research on protein structure and function has provided remarkable insights into the relative roles of physics and evolution in dictating the properties of protein structure and function and holds the potential to dramatically accelerate and enhance the drug discovery process.
“Jeff is a world-class scientist with tremendous imagination and creativity,” stated Terry Snell, Chair of the School of Biology at Georgia Tech. “His research has significantly enhanced our understanding of protein structure and function.”
Over his career, Skolnick has made significant scientific contributions. He developed the first coarse grained model for protein structure prediction, the first successful multiscale modeling approach to structure prediction, the first effective medium model for a membrane that enabled the successful prediction of peptide orientation and conformation with respect to the membrane, Fuzzy Functional Forms that were the first low resolution approach to protein function prediction, and the highly accurate EFICAz approach to enzyme function inference. His more recent work has significant applications to both drug discovery and to improving our fundamental understanding of the possible origin of life.
The SURA Distinguished Scientist Award was established in 2007 to commemorate the organization’s 25th Anniversary and is considered its highest honor. SURA’s Development & Relations Committee manages the solicitation, screening and selection of the recipient for this award from a SURA member institution.
By inferring and resurrecting ancient sequences for an enzyme called uricase, the group was able to determine when and why the enzyme stop functioning in apes (including humans) while remaining functional in most other mammals. See the following link for an insightful article written by National Geographic: http://phenomena.nationalgeographic.com/2014/02/17/a-resurrected-cretaceous-answer-to-the-disease-of-kings/
Congratulations to the following faculty and staff members who were honored at the 2014 Faculty and Staff Honors Luncheon on April 11.
Georgia Tech Chapter Sigma Xi Awards
Young Faculty Awards
Satish Kumar, Mechanical Engineering
Christopher Rozell, Electrical and Computer Engineering
Sustained Research Award
C.F. Jeff Wu, Industrial and Systems Engineering
Institute Research Awards
Outstanding Achievement in Research Enterprise Enhancement
Mary Hallisey Hunt, Strategic Energy Institute
Outstanding Achievement in Research Innovation
Mark Prausnitz, Chemical and Biomolecular Engineering
Outstanding Doctoral Thesis Advisor
John Cressler, Electrical and Computer Engineering
Outstanding Faculty Leadership for the Development of Graduate Research Assistants
Kenneth Sandhage, Materials Science and Engineering
Outstanding Faculty Research Author
Seth Marder, Chemistry and Biochemistry
Outstanding Achievement in Research Program Development
Gang Bao, Biomedical Engineering
Christine Valle, College of Engineering
Outstanding Staff Performance Awards
Phyllis Means, Office of the Executive Vice President for Research
David Knobbe and Matthew Marcus, Campus Recreation Center
D. Matthew Watkins, Georgia Tech Police Department
Dustin Hamilton, Campus Recreation Center
Stephanie Ray, Dean of Students
Outstanding Management in Action Award
Marc Pline, Biology
Administrative Excellence Award
David Williams, Campus Recreation Center
Undergraduate Educator Awards
Michael Rodgers, Civil and Environmental Engineering
Chrissy Spencer Biology
Innovation and Excellence in Laboratory Instruction Award
Essy Behravesh, Biomedical Engineering
CETL/BP Junior Faculty Teaching Excellence Awards
J. Brandon Dixon, Mechanical Engineering
Flavio Fenton, Physics
Brian Hammer, Biology
Kamran Paynabar, Industrial and Systems Engineering
Anne Pollock, Literature, Media, and Communication
Kari E. Watkins, Civil and Environmental Engineering
Education Partnership Awards
Eric Gaucher, School of Biology
Ryan Randall, School of Biology
Curriculum Innovation Award
Amy Pritchett, Aerospace Engineering
Innovation in Co-Curricular Education Award
Jennifer Leavey, College of Sciences
Faculty Award for Academic Outreach
Stefan France, Chemistry and Biochemistry
Eichholz Faculty Teaching Awards
Linda Green, Biology
Donald Webster, Civil and Environmental Engineering
Steven A. Denning Faculty Award for Global Engagement
Michael Best, International Affairs
Academic Advisor Awards
Outstanding Undergraduate Academic Advising: Staff
Kim Paige, Biomedical Engineering
Outstanding Undergraduate Academic Advising: Faculty
Linda Green, Biology
Faculty Honors Committee Awards
Outstanding Undergraduate Research Mentor (Faculty) Award
Margaret Kosal, International Affairs
Kenneth Gall, Materials Science and Engineering
Outstanding Professional Education Award
A.P. Sakis Meliopoulos, Electrical and Computer Engineering
Outstanding Service Award
Michael Hunter, Civil and Environmental Engineering
Class of 1934 Outstanding Innovative Use of Education Technology Award
James Hamblen, Electrical and Computer Engineering
Class of 1934 Outstanding Interdisciplinary Activity Award
Bernard Kippelen, Electrical and Computer Engineering
Class of 1940 W. Howard Ector Outstanding Teacher Award
Joel Sokol, Industrial and Systems Engineering
Class of 1940 W. Roane Beard Outstanding Teacher
Mike Stilman, Interactive Computing
Class of 1934 Distinguished Professor Award
Zhong Lin Wang, Materials Science and Engineering
Monica’s research will focus on a systems biology approach towards the developing of a malaria vaccine. Using gene expression profiling of the human immune response to malaria vaccination, Monica hopes to investigate the safety and efficacy of vaccines, along with the most effective strategies of vaccine implementation. The Schlumberger Foundation is a prestigious foundation, which selects outstanding women from developing counters to aid in their pursuit of graduate studies in engineering, science and technology disciplines worldwide. Grant recipients are selected both for their leadership capabilities and scientific talents. Ultimately they are expected to return to their home country’s to become inspiration role models and disseminate the information gained during their studies. Monica is from Colombia and her research has direct impact into her home country, as malaria is one of the major public health problems of the tropics.
Fish living on coral reefs where carbon dioxide seeps from the ocean floor were less able to detect predator odor than fish from normal coral reefs, according to a new study.
The study confirms laboratory experiments showing that the behavior of reef fishes can be seriously affected by increased carbon dioxide concentrations in the ocean. The new study is the first to analyze the sensory impairment of fish from CO2 seeps, where pH is similar to what climate models forecast for surface waters by the turn of the century.
"These results verify our laboratory findings," said Danielle Dixson, an assistant professor in the School of Biology at the Georgia Institute of Technology in Atlanta. "There's no difference between the fish treated with CO2 in the lab in tests for chemical senses versus the fish we caught and tested from the CO2 reef."
The research was published in the April 13 Advance Online Publication of the journal Nature Climate Change. Philip Munday, from James Cook University in Australia, was the study's lead author. The work was supported by the Australian Institute for Marine Science, a Grant for Research and Exploration by the National Geographic Society, and the ARC Centre of Excellence for Coral Reef Studies.
The pH of normal ocean surface water is around 8.14. The new study examined fish from so-called bubble reefs at a natural CO2 seep in Papua New Guinea, where the pH is 7.8 on average. With today's greenhouse gas emissions, climate models forecast pH 7.8 for ocean surface waters by 2100, according to theIntergovernmental Panel on Climate Change (IPCC).
"We were able to test long-term realistic effects in this environment," Dixson said. "One problem with ocean acidification research is that it's all laboratory based, or you're testing something that's going to happen in a 100 years with fish that are from the present day, which is not actually accurate."
Previous research had led to speculation that ocean acidification might not harm fish if they could buffer their tissues in acidified water by changing their bicarbonate levels. Munday and Dixson were the first to show that fishes' sensory systems are impaired under ocean acidification conditions in the laboratory.
"They can smell but they can't distinguish between chemical cues," Dixson said.
Carbon dioxide released into the atmosphere is absorbed into ocean waters, where it dissolves and lowers the pH of the water. Acidic waters affect fish behavior by disrupting a specific receptor in the nervous system, called GABAA, which is present in most marine organisms with a nervous system. When GABAA stops working, neurons stop firing properly.
Coral reef habitat studies have found that CO2-induced behavioral changes, similar to those observed in the new study, increase mortality from predation by more than fivefold in newly settled fish.
Fish can smell a fish that eats another fish and will avoid water containing the scent. In Dixson's laboratory experiments, control fish given the choice between swimming in normal water or water spiked with the smell of a predator will choose the normal water. But fish raised in water acidified with carbon dioxide will choose to spend time in the predator-scented water.
Juvenile fish living at the carbon dioxide seep and brought onto a boat for behavior testing had nearly the identical predator sensing impairment as juvenile fish reared at similar CO2 levels in the lab, the new study found.
The fish from the bubble reef were also bolder. In one experiment, the team measured how far the fish roamed from a shelter and then created a disturbance to send the fish back to the shelter. Fish from the CO2 seep emerged from the shelter at least six times sooner than the control fish after the disturbance.
Despite the dramatic effects of high CO2 on fish behaviors, relatively few differences in species richness, species composition and relative abundances of fish were found between the CO2 seep and the control reef.
"The fish are metabolically the same between the control reef and the CO2 reef," Dixson said. "At this point, we have only seen effects on their behavior."
The researchers did find that the number of large predatory fishes was lower at the CO2 seep compared to the control reef, which could offset the increased risk of mortality due to the fishes' abnormal behavior, the researchers said.
In future work, the research team will test if fish could adapt or acclimate to acidic waters. They will first determine if the fish born at the bubble reef are the ones living there as adults, or if baby fish from the control reef are swimming to the bubble reef.
"Whether or not this sensory effect is happening generationally is something that we don't know," Dixson said.
The results do show that what Dixson and colleagues found in the lab matches with what is seen in the field.
"It's a step in the right direction in terms of answering ocean acidification problems." Dixson said. "The alternative is just to wait 100 years. At least now we might prepare for what might be happening."
This research is supported by the Australian Institute for Marine Science, a Grant for Research and Exploration by the National Geographic Society, and the ARC Centre of Excellence for Coral Reef Studies. Any conclusions or opinions are those of the authors and do not necessarily represent the official views of the sponsoring agencies.
CITATION: Philip L. Munday, et al., "Behavioural impairment in reef fishes caused by ocean acidification at CO2 seeps." (Nature Climate Change, April 2014). http://dx.doi.org/10.1038/NCLIMATE2195
Georgia Institute of Technology
177 North Avenue
Atlanta, Georgia 30332-0181 USA
Writer: Brett Israel
From time to time, living cells will accidently make an extra copy of a gene during the normal replication process. Throughout the history of life, evolution has molded some of these seemingly superfluous genes into a source of genetic novelty, adaptation and diversity. A new study shows one way that some duplicate genes could have long-ago escaped elimination from the genome, leading to the genetic innovation seen in modern life.
Researchers have shown that a process called DNA methylation can shield duplicate genes from being removed from the genome during natural selection. The redundant genes survive and are shaped by evolution over time, giving birth to new cellular functions.
“This is the first study to show explicitly how the processes of DNA methylation and duplicate gene evolution are related,” said Soojin Yi, an associate professor in the School of Biology and the Parker H. Petit Institute for Bioengineering and Bioscience at the Georgia Institute of Technology.
The study was sponsored by the National Science Foundation (NSF) and was scheduled to be published the week of April 7 in the Online Early Edition of the journal Proceedings of the National Academy of Sciences (PNAS).
At least half of the genes in the human genome are duplicates. Duplicate genes are not only redundant, but they can be bad for cells. Most duplicate genes accumulate mutations at high rates, which increases the chance that the extra gene copies will become inactive and lost over time due to natural selection.
The new study found that soon after some duplicate genes form, small hydrocarbons called methyl groups attach to a duplicate gene’s regulatory region and block the gene from turning on.
When a gene is methylated, it is shielded from natural selection, which allows the gene to hang around in the genome long enough for evolution to find a new use for it. Some young duplicate genes are silenced by methylation almost immediately after being formed, the study found.
“What we have done is the first step in the process to show that young gene duplicates seems to be heavily methylated,” Yi said.
The study showed that the average level of DNA methylation on the duplicate gene regulatory region is significantly negatively correlated with evolutionary time. So, younger duplicate genes have high levels of DNA methylation.
For about three-quarters of the duplicate gene pairs studied, the gene in a pair that was more methylated was always more methylated across all 10 human tissues studied, said Thomas Keller, a post-doctoral fellow at Georgia Tech and the study’s first author.
“For the tissues that we examined, there was remarkable consistency in methylation when we looked at duplicate gene pairs,” Keller said.
The computational study constructed a dataset of all human gene duplicates by comparing each sequence against every other sequence in the human genome. DNA methylation data was then obtained for the 10 different human tissues. The researchers used computer models to analyze the links between DNA methylation and gene duplication.
The human brain is one example of a tissue for which gene duplication has been particularly important for its evolution. In future studies, the researchers will examine the link between epigenetic evolution and human brain evolution.
This research is supported by the National Science Foundation (NSF) under award numbers BCS-1317195 and MCB-0950896. Any conclusions or opinions are those of the authors and do not necessarily represent the official views of the sponsoring agency.
CITATION: Thomas E. Keller, et al., “DNA Methylation and Evolution of Duplicate Genes.” (PNAS, April 2014). http://www.dx.doi.org/10.1073/pnas.1321420111
Georgia Institute of Technology
177 North Avenue
Atlanta, Georgia 30332-0181 USA
Writer: Brett Israel
Populations of predators and their prey usually follow predictable cycles. When the number of prey increases, perhaps as their food supply becomes more abundant, predator populations also grow.
When the predator population becomes too large, however, the prey population often plummets, leaving too little food for the predators, whose population also then crashes. This canonical view of predator-prey relationships was first identified by mathematical biologists Alfred Lotka and Vito Volterra in the 1920s and 1930s.
But all bets are off if both the predator and prey species are evolving in even small ways, according to a new study published this week in the journal Proceedings of the National Academy of Sciences. When both species are evolving, the traditional cycle may reverse, allowing predator populations to peak before those of the prey. In fact, it may appear as if the prey are eating the predators.
Researchers at the Georgia Institute of Technology have proposed a theory to explain these co-evolutionary changes. And then, using data collected by other scientists on three predator-prey pairs – mink-muskrat, gyrfalcon-rock ptarmigan and phage-Vibrio cholerae – they show how their theory could explain unexpected population cycles.
The new theory and analysis of these co-evolution cycles could help epidemiologists predict cycles of disease and the virulence of infectious agents, and lead to a better understanding of how population cycles may affect ecosystems. The research was supported by the National Science Foundation and the Burroughs Wellcome Fund.
“Our work shows that co-evolution can yield new and unique behavior at the population scale,” explained Joshua Weitz, an associate professor in the School of Biology at Georgia Tech. “When you include evolution, the classic prey-predator dynamics have a much greater range of possible outcomes. We are not replacing the original theory, but proposing a more general model that opens the door to these new phenomena.”
Evolution is often perceived as an historical event, noted Weitz, who also has a courtesy appointment in the Georgia Tech School of Physics. But organisms are evolving continuously, with certain phenotypes becoming dominant as environmental and other conditions favor them. In organisms such as birds or small mammals, those changes can be manifested in as few as ten generations. In microbial species with brief lifespans, evolutionary changes can happen within days or weeks.
Evolutionary changes can dramatically affect relationships between species, potentially making them more vulnerable or less vulnerable. For instance, if a mutation that confers viral resistance in a species of bacteria becomes dominant, that may change the predator-prey relationship by rendering the bacteria population safe from harm. More generally, co-evolutionary cycles can arise when predator offense is costly and prey defense is effective against low offense predators.
“With predator and prey co-evolution, you can see oscillations in which there are lots of prey around even when there are many predators, or lots of predators around even when there are very few prey,” noted Michael Cortez, a postdoctoral fellow in the Weitz lab and first author of the paper.
“When prey is abundant and there are few predators, it may be because there are many defended prey – prey that the predators can’t eat,” he added. “When there are lots of predators around and few prey, it’s because the prey are very good food sources and the predators are doing quite well.”
In their paper, Weitz and Cortez simulated models in which the evolutionary process was sped up to show how their theory of co-evolution would affect predator-prey population cycles. Speeding up the process allowed them to break the cycle up into smaller segments that could be analyzed in more detail. They then used the earlier observations of the changing abundances of the three pairs of predators and prey -- leveraging data sets collected by other scientists – to show how the models would apply.
“Although the structure of the cycles in these three systems had been noted as unusual by the authors who observed them, there had been, as yet, no unified theoretical framework from which to make sense of such as radical departure from the classic signature of predator-prey interactions,” Weitz said.
Scientists have long studied how the interaction between species affects overall populations in ecosystems. Weitz and Cortez believe their new model will give scientists a broader and more complete picture of the complex process.
“This study identifies how adaptation between two species and interactions between their numbers can result in something different from what you would get if you just had the interaction between the numbers,” said Cortez. “This is something that will show up across many ecological systems. We can now explain broad trends that occur in vastly different systems using a theoretical approach, and the fact that we can identify the mechanism responsible for it is unique to our study.”
This research was supported by the National Science Foundation under Award DMS-1204401, and by the Burroughs Wellcome Fund. Any conclusions or opinions expressed are those of the authors and do not necessarily represent the official views of the sponsoring agencies.
CITATION: Michael H. Cortez and Joshua S. Weitz, “Coevolution Can Reverse Predator-Prey Cycles,” (Proceedings of the National Academy of Sciences, 2014). www.pnas.org/cgi/doi/10.1073/pnas.1317693111
Georgia Institute of Technology
177 North Avenue
Atlanta, Georgia 30332-0181 USA
Media Relations Contacts: John Toon (404-894-6986) (email@example.com) or Brett Israel (404-385-1933) (firstname.lastname@example.org).
Writer: John Toon