Slow motion waves of jumping genes in the human genome

Claudia Lutz, Institute for Genomic Biology
11/14/2016 1:08 PM

New Illinois study makes detailed predictions about an intriguing mechanism of genomic evolution

Swanlund Professor of Physics Nigel Goldenfeld and graduate research assistant Chi Xue, Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign
Swanlund Professor of Physics Nigel Goldenfeld and graduate research assistant Chi Xue, Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign
Nature is full of parasites—organisms that flourish and proliferate at the expense of another species. Surprisingly, these same competing roles of parasite and host can be found in the microscopic molecular world of the cell. A new study by two Illinois researchers has demonstrated that dynamic elements within the human genome interact with each other in a way that strongly resembles the patterns seen in populations of predators and prey.

The findings, published in Physical Review Letters by physicists Chi Xue and Nigel Goldenfeld, (DOI: 10.1103/PhysRevLett.117.208101) are an important step toward understanding the complex ways that genomes change over the lifetime of individual organisms, and how they evolve over generations.

“These are genes that are active and are doing genome editing in real time in living cells, and this is a start of trying to really understand them in much more detail than has been done before,” said Goldenfeld, who leads the Biocomplexity research theme at the Carl R. Woese Institute for Universal Biology (IGB). “This is helping us understand the evolution of complexity and the evolution of genomes.”

The study was supported by Center for the Physics of Living Cells, a Physics Frontiers Center at Illinois supported by the National Science Foundation, and the NASA Astrobiology Institute for Universal Biology at Illinois, which Goldenfeld directs.

Goldenfeld and Xue embarked on this work because of their interest in transposons, small regions of DNA that can move themselves from one part of the genome to another during the lifetime of a cell—a capability that has earned them the name “jumping genes.” Collectively, various types of transposons make up almost half of the human genome. When they move around, they may create mutations in or alter the activity of a functional gene; transposons can therefore create new genetic profiles in a population for natural selection to act on, in either a positive or negative way.

The Illinois researchers wanted to learn more about how evolution works on this level, the level of whole organisms, by looking at the metaphorical ecosystem of the human genome. In this view, the physical structure of the DNA that makes up the genome acts like an environment, in which two types of transposons, long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), have a competitive relationship with one another. In order to replicate, SINEs steal the molecular machinery that LINEs use to copy themselves, somewhat like a cuckoo bird tricks other birds into raising her chicks for her while abandoning their own.

With help from Oleg Simakov, a researcher at the Okinawa Institute of Science and Technology, Xue and Goldenfeld focused on the biology of L1 elements and Alu elements, respectively common types of LINEs and SINEs in the human genome.

The researchers adopted methods from modern statistical physics and modeled the interaction between Alu and L1 elements mathematically as a stochastic process—a process created from chance interactions. This method has been successfully applied in ecology to describe predator-prey interactions; Xue and Goldenfeld simulated the movements of transposons within the human genome with the same mathematical method. Their models included a detailed accounting for how Alu elements steal the molecular machinery L1 elements use to copy themselves.

Xue and Goldenfeld’s results predicted that populations of LINE and SINE elements in the genome are expected to oscillate the way those of, for example, wolves and rabbits might.

“We realized that the transposons’ interaction actually was pretty much like the predator-prey interaction in ecology,” said Xue. “We came up with the idea, why don’t we apply the same idea of predator-prey dynamics . . .we expected to see the oscillations we see in the predator-prey model. So we first did the simulation and we saw the oscillations we expected, and we got really excited.”

In other words, too many SINEs and the LINEs start to suffer, and soon there are not enough for all the SINEs to exploit.  SINEs start to suffer, and the LINEs make a come-back. Xue and Goldenfeld’s model made the surprising prediction that these oscillations occur over a timescale that is longer than the human lifespan—waves of Alu elements and L1 elements pushing and pulling at each other in slow motion across generations of the human genomes that carry them.

“The most enlightening aspect of the study for me was the fact that we could really compute the timescales, and see that it is possible that we could observe these things,” said Goldenfeld. “We have a prediction for what happens in single cells, and we may be able to actually do an experiment to observe these things, though the period is longer than the lifetime of a single cell.”

In a related study, Goldenfeld’s laboratory has collaborated with the laboratory of fellow physicist and IGB Biocomplexity research theme member Thomas Kuhlman to visualize the movements of transposons within the genomes of living cells (link: Using this type of innovative technology, and by studying the history of molecular evolution in other species, Goldenfeld and Xue hope to test some of the predictions made by their model and continue to gain insight into the dynamic world of the genome.


Recent News

It took two years on a supercomputer to simulate 1.2 microseconds in the life of the HIV capsid, a protein cage that shuttles the HIV virus to the nucleus of a human cell. The 64-million-atom simulation offers new insights into how the virus senses its environment and completes its infective cycle.

The findings are reported in the journal Nature Communications.

  • Accolades

The Center for Advanced Study has appointed seven new members to its permanent faculty – one of the highest forms of academic recognition the University of Illinois campus makes for outstanding scholarship. The new CAS Professors are Antoinette Burton, history; Gary Dell, psychology; Eduardo Fradkin, physics; Martin Gruebele, chemistry; Sharon Hammes-Schiffer, chemistry; Harry Liebersohn, history; and Catherine Murphy, chemistry. They join 21 other CAS Professors with permanent appointments, and they will remain full members of their home departments while also serving on the annual selection committee for the CAS Associates and Fellows program.

  • In the Media
  • Biological Physics

A common bacteria is furthering evidence that evolution is not entirely a blind process, subject to random changes in the genes, but that environmental stressors can also play a role. A NASA-funded team is the first group to design a method demonstrating how transposongs-DNA sequences that move positions within a genome-jump from place to place. The researchers saw that the jumping rate of these transposons, aptly-named "jumping genes" increases or decreases depending on factors in the environment, such as food supply.

  • Research
  • Condensed Matter Physics
  • Condensed Matter Theory
  • ICMT
  • Institute for Condensed Matter Theory

Researchers at the University of Illinois at Urbana-Champaign and Princeton University have theoretically predicted a new class of insulating phases of matter in crystalline materials, pinpointed where they might be found in nature, and in the process generalized the fundamental quantum theory of Berry phases in solid state systems. What’s more, these insulators generate electric quadrupole or octupole moments—which can be thought of roughly as very specific electric fields—that are quantized. Quantized observables are a gold standard in condensed matter research, because experimental results that measure these observables have to, in principle, exactly match theoretical predictions—leaving no wiggle room for doubt, even in highly complex systems.

The research, which is the combined effort of graduate student Wladimir Benalcazar and Associate Professor of Physics Taylor Hughes of the Institute for Condensed Matter Theory at the U. of I., and Professor of Physics B. Andrei Bernevig of Princeton, is published in the July 7, 2017 issue of the journal Science.