Category Archives: Transhuman News

Patterns arent the only way to inspire coperation. In 2018, Levins team attached a plastic cuff containing progesterone, a hormone that alters the behavior of ion channels, to the stump where a frog had once had a leg. They left the cuff on for twenty-four hours, then observed for about a year. Ordinarily, a frog thats lost a leg will regrow a cartilaginous spike in its place. But the frogs in the experiment grew paddle-like limbs. About nine months later, little toes started to emerge. Levin thinks that, eventually, the same kind of cuff could be used on humans; you might wear one for a few months, long enough to persuade your body to restart its growth. (Ideally, researchers would find a way to speed development, too; otherwise, youd be stuck with a tiny arm for years.)

Levin was wary of showing me any mouse experiments. He has growntired of hearing his work compared to the sinister alchemy described in Frankenstein. That story is about scientific irresponsibility, he said. Although his research is in many ways unusual, it is ordinary in its treatment of animalsby some estimates, American researchers experiment on more than twenty-five million a year. I get two types of e-mails and phone calls, Levin told me. Some of the people call and say, How dare you do these things? for various reasonsanimal rights, playing God, whatever. And then most call and they say, What the fuck is taking you so long? From time to time, Levin receives a call from a would-be volunteer. Im going to come down to your lab, he recalled one of them saying, and Ill be your guinea pig. I want my foot back.

None of the developmental biologists I spoke with expressed any doubt that we would someday be able to regrow human limbs. They disagreed only about how long it would take us to get there, and about how, exactly, regrowth would work. Other projects explore growing body parts in labs for transplantation; 3-D-printing them whole, using tissue cells; flipping genetic switches (master regulators); or injecting stem cells into residual limbs. The solution may eventually involve a medley of techniques.

Levins vision isnt confined to limb regrowth; hes interested in many other forms of morphogenesis, or tissue formation, and in how they can be modelled using computers. He led me down the hall to a room where an elaborate, waist-high machine glowed. The device consisted of twelve petri dishes suspended above an array of lights and cameras, which were hooked up to a cluster of high-powered computers. He explained that the system was designed to measure tadpole and planarian I.Q.

In a study published in 2018, Levins team bathed frog embryos in nicotine. As they expected, the frogs exhibited a range of neural deformities, including missing forebrains. The researchers then used a piece of software called BETSEthe BioElectric Tissue Simulation Enginethat a member of the Allen Center, Alexis Pietak, had built. In this virtual world, they applied various drugs and observed their effects on both bioelectric signalling and brain development, hoping to find an intervention that would reverse the nicotines damage. The software made a prediction that one specific type of ion channel can be exploited for just such an effect, Levin said. The team tried the drug on real embryos that had been damaged by nicotine, and found that their brains rearranged themselves into the proper shape. The software, the researchers wrote, had allowed for a complete rescue of brain morphology.

The I.Q. machine gave them another way to measure the extent of the rescue. Inside it, colored L.E.D.s illuminate petri dishes from below, dividing them into zones of red and blue; when a grown tadpole ventures into the red, it receives a brief shock. Levin found that normal tadpoles uniformly learned to avoid the red zones, while those that had been exposed to nicotine learned to do so only twelve per cent of the time. But those treated with the bioelectricity-recalibrating drug learned eighty-five per cent of the time. Their I.Q.s recovered.

Researchers disagree about the role that bioelectricity plays in morphogenesis. Laura Borodinsky, a biologist who studies development and regeneration at the University of California, Davis, told me that there are many things that we still need to discover about how the process works, including how the genetic program and the bioelectrical signals are intermingled. Tom Kornberg, a biochemist at the University of California, San Francisco, studies another intercellular system that is similar to bioelectricity; it consists of morphogens, special proteins that cells release in order to communicate with one another. Kornbergs lab investigates how morphogens move among cells and tell them what to do. What is the vocabulary? Whats the language? Kornberg said, in reference to morphogenesis. There is probably more than one.

Tabin, Levins former adviser and the chair of genetics at Harvard Medical School, told me that he is agnostic about how bioelectricity should be understood. Levin describes bioelectricity as a code. But, Tabin said, theres a difference between being a trigger to initiate morphogenesis versus storing information in the form of a code. He offered an analogy. Electricity is required to run my vacuum cleaner, he said. It doesnt mean theres necessarily an electric code for vacuuming. The current flowing through the outlet isnt telling the vacuum what to do. Its just turning it on.

Levin thinks that bioelectricity is more complex than that. The right bioelectrical signal can transform a Dustbuster into a Dysonor a tail into a head. Tweaking the signal produces highly specific outcomesa head thats spiky, tubular, or hat-shapedwithout the need to adjust individual genes, ion channels, or cells. You can hack thesystem to make the changes, Levin said. Currently, theres no competing technology that can do these things.

Levins work has philosophical dimensions. Recently, he watched Ex Machinaa sci-fi film, directed by Alex Garland, in which a young programmer is introduced to Ava, a robot created by his tech-mogul boss. Unnerved by how beguilingly realistic Ava is, the hero slices his own arm open in search of wires. Since childhood, Levin, too, has wondered what we are made of; having become a father himself, he enjoys talking about such questions with his sons, who are now teen-agers. Once, when his older son was six or seven, Levin asked him how a person could be sure that he hadnt been created mere seconds ago, and provided with a set of implanted memories. I didnt really think about what the consequences for a kid might be, Levin said, laughing and a little embarrassed. He was upset for about a week.

Our intuitions tell us that it would be bad to be a machine, or a group of machines, but Levins work suggests precisely this reality. In his world, were robots all the way down. A bioelectrical signal may be able to conjure an eye out of a stomach, but eye-making instructions are contained neither in the cells genome nor in the signal. Instead, both collectively and individually, the cells exercise a degree of independence during the construction process.

The philosopher Daniel Dennett, who is Levins colleague at Tufts, has long argued that we shouldnt distinguish too sharply between the sovereign, self-determining mind and the brute body. When we spoke, Dennett, who has become one of Levins collaborators, was in bed at a Maine hospital, where he was recovering from hip surgery. I find it very comforting to reflect on the fact that billions of little agents are working 24/7 to restore my muscles, heal my wounds, strengthen my legs, he said.

In our discussion of Levins work, Dennett asked me to imagine playing chess against a computer. He told me that there were a few ways I could look at my opponent. I could regard it as a metal box filled with circuits; I could see it as a piece of software, and inspect its code; and I could relate to it as a player, analyzing its moves. In reality, of course, a chess computer offers more than three levels of explanation. The body allows more still: genetics, biophysics, biochemistry, bioelectricity, biomechanics, anatomy, psychology, and finer gradations in between, all these levels acting together, each playing an integral role. Levin doesnt claim to understand the entire system, nor does he maintain that bioelectricity is the only important level. Its just one where hes found some leverage. He likens revising an organisms body through bioelectric stimulation to launching software applications. When you want to switch from Photoshop to Microsoft Word, you dont get out your soldering iron, he said.

In modifying the body, Levin is more whisperer than micromanager; he makes suggestions, then lets the cells talk among themselves. Michael has these brilliant examples of how individual cells communicate with each other, Dennett said. But the reverse is also true: when communication breaks down, cells can go haywire. Consider cancer, Levin said. It can be created by genetic damage, but also by disruptions in bioelectric voltage. In an experiment reported in 2016, Levins team injected cancer-causing mRNA into frog embryos, and found that injected areas first lost their electrical polarity, then developed tumor-like growths. When the researchers counteracted the depolarization, some of the tumors disappeared. In Levins terms, the cancer cells had lost the thread of the wider conversation, and begun to reproduce aimlessly, without coperating with their neighbors. Once communications had been restored, they were able to make good decisions again.

Having built radios as a kid, Levin now hopes to assemble bodies from first principles. His ultimate goal is to build what he calls an anatomical compilera biological-design program in which users can draw the limbs or organs they want; the software would tell them where and how to modify an organisms bioelectric gradients. You would say, Well, basically like a frog, but Id like six legsand Id like a propeller over here, he explained. Such a system could fix birth defects, or allow the creation of new biological shapes that havent evolved in nature. With funding from DARPAa federal research agency contained within the Department of Defensehe is exploring a related possibility: building machines made from animal cells. Recently, Josh Bongard, a computer scientist at the University of Vermont, designed a computer model in which small robotic cubes connect, creating microrobots that might someday clean up toxic waste or perform microsurgery. Levin took stem and cardiac cells from frogs and sculpted them into blobs that approximated the robot designs; they began working together, matching the simulations. Bongard likened Levin to a magician pulling rabbits out of a hat. After a while, you start asking not just whats in the hat, he said, but how deep does the inside of that hat go?

On a warm afternoon, Levin and I drove out to Middlesex Fells Reservationa twenty-six-hundred-acre state park with more than a hundred miles of trails. We set out through the woods along Spot Pond, a large reservoir where people sail and kayak in the summer. As we walked, our bodies worked up a light sweat. Occasionally, Levin stopped to wonder at fungi clinging to a tree trunk, or to look under a rock for creepy crawlies. Spotting an ant, he recalled trying to feed ants as a child and being surprised at their stubbornness. He noted that planaria can have different personalitieseven clones of the same worm. He interrupted his comments on neural decoding to study a plant. Look at the colors on these berries, he said. What the hell? Ive never seen that before. It looks almost like candy. Let me get a picture of this.

I jokingly asked Levin if, when looking at nature, he saw computer code raining down, as in The Matrix. Thats a funny question, he said. I do not see the Matrix code, but Im often taking pictures or kayaking or something, and thinking about this stuff. I asked him if he saw squirrels and trees differently from the way others do. Not a squirrel, he said, because everyone recognizes it as a cognitive agenta system with beliefs and desires. But a cell or a plant, for sure.

I look everywhere, and I ask the question Whats the cognitive nature of this system? Whats it like to be a He paused. Whats your sensory world like, what decisions are you making, what memories do you have, if any? What predictions do you make? Do you anticipate future events? Slime molds can anticipate regular stimuli. I look for cognition everywhere. In some places you dont find it, and thats fine, but I think I see it broader than many people.

We stopped to look at a log and found a red splotch that appeared to be a slime mold.

I dont know what it actually is, Levin said. Im not much of a zoologist.

Bending down, he peeled off some bark: a second splotch. Researchers have found that, if a slime mold learns something and then crawls over and touches another mold, it can pass on its memory; in 2016, a pair of French scientists showed how one mold could teach another to find some hard-to-reach food through a gooey mind meld.

That, I think about all the time, Levin said. What does it mean to encode information in a way that, almost like a brain transplant, you can literally give it to another creature?

We left the log and continued on. Lichen spotted the rocks, and chipmunks chattered in the trees. There was electricity all around us.

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Is Bioelectricity the Key to Limb Regeneration? - The New Yorker

IntramuralBy Nicholas Alagna, Victoria Placentra, Prashant Rai, Janelle Weaver, and Qing Xu

Scientists from the Division of the National Toxicology Program (DNTP) uncovered a new strategy that could estimate the safety of chemicals. Using benchmark concentration (BMC) analysis with human liver cells, the team determined that different concentrations of compounds caused changes in detectable metabolites produced by liver cells. The project used metabolomics, which is the large-scale detection and measurement of metabolites the molecules that are intermediates or end products after the body breaks down food, drugs, or chemicals.

The researchers applied concentration-response modeling using BMC analysis to interpret mass spectrometry-based untargeted metabolomics data. Concentration-response modeling assesses how exposure to various concentrations of toxic chemicals and other compounds leads to changes in metabolites. The team exposed cultures of human liver cells to compounds that included relatively toxic drugs such as the cancer drug tamoxifen and the antiretroviral medication ritonavir.

Rising concentrations of drugs known to cause liver injury resulted in sharp increases in metabolic responses that were expected based on past research. By contrast, this effect did not occur for nontoxic compounds, such as sucrose and potassium chloride. According to the authors, the study shows that concentration-response modeling applied to untargeted metabolomics data accurately captures the potential of chemicals to cause liver injury. (JW)

Citation:Crizer DM, Ramaiahgari SC, Ferguson SS, Rice JR, Dunlap PE, Sipes NS, Auerbach SS, Merrick BA, DeVito MJ. 2021. Benchmark concentrations for untargeted metabolomics vs. transcriptomics for liver injury compounds in in vitro liver models. Toxicol Sci; doi: 10.1093/toxsci/kfab036 [Online 22 March 2021].

According to NIEHS researchers and their collaborators, the mosquito protein AEG12 disrupts the lipid envelope that covers some viruses. The study sheds light on the molecular mechanism AEG12 uses to inhibit virus infection, as well as offering potential new strategies to treat dangerous diseases caused by flaviviruses.

Flaviviruses a class that includes dengue, yellow fever, and zika virus are important public health concerns. These viruses are mainly transmitted by mosquitos and typically covered by a protective coating of lipids. Mosquitos produce AEG12 in response to a blood meal or flavivirus infection.

After solving the three-dimensional structure of AEG12 by X-ray crystallography, the researchers identified AEG12 as a lipid-binding protein. They further demonstrated that AEG12 was capable of rupturing membranes of red blood cells and inhibiting the replication of flaviviruses and other enveloped viruses, including human coronaviruses. AEG12 breaks open the cells or virus by swapping the lipid it carries with those in the cell membrane or virus envelop. By doing so, AEG12 contributes to both insect digestion and the antiviral immune response. The study suggests that AEG12, if engineered to target the virus only, may provide a useful tool to treat diseases caused by flaviviruses or coronaviruses. (QX)

Citation:Foo ACY, Thompson PM, Chen SH, Jadi R, Lupo B, DeRose EF, Arora S, Placentra VC, Premkumar L, Perera L, Pedersen LC, Martin N, Mueller GA. 2021. The mosquito protein AEG12 displays both cytolytic and antiviral properties via a common lipid transfer mechanism. Proc Natl Acad Sci U S A 118(11):e2019251118. (Story)

The progesterone receptor isoform B (PGR-B) mediates suppression of uterine contractibility via the Oxtr-Plcl2-Trpc3 pathway, according to NIEHS researchers and their collaborators. In humans, the progesterone receptor is a nuclear receptor with two isoforms: PGR-A and PGR-B. Elevated PGR-B gives rise to longer gestational periods, extended labor time, greater incidence of labor dystocia, or difficult birth, and a reduction in uterine contractility. PGR-A, however, promotes contractility of the uterus, without altering gestation length. To explore the in vivo role of progesterone signaling and progesterone receptor (PGR) isoforms in childbirth, the team employed transgenic mice with an overexpression of PGR-A or PGR-B in their myometrial smooth muscle.

Gene signature analyses demonstrated that PGR-A acts in a proinflammatory fashion, while PGR-B causes uterine muscle relaxation. Transcriptomic investigation revealed that PGR-B mice exhibit repression of both the Oxtr and Trpc3 genes, which both have a positive effect on uterine contractility. Furthermore, PGR-B mice displayed increased expression of the Plcl2 gene, which can reduce uterine contraction. These findings further explain precise molecular mechanisms by which PGR isoforms govern childbirth, while contributing novel insights into the maintenance of uterine dormancy by progesterone during pregnancy. (NA)

Citation:Peavey MC, Wu SP, Li R, Liu J, Emery OM, Wang T, Zhou L, Wetendorf M, Yallampalli C, Gibbons WE, Lydon JP, DeMayo FJ. 2021. Progesterone receptor isoform B regulates the Oxtr-Plcl2-Trpc3 pathway to suppress uterine contractility. Proc Natl Acad Sci U S A 118(11):e2011643118. (Story)

NIEHS scientists and collaborators at the National Cancer Institute and Duke University have uncovered the detailed mechanism by which a metabolic enzyme called PPIP5K can directly regulate tumor cell multiplication. The study helps explain the metabolic reprogramming required for multiplication of tumor cells and reveals potential targets for cancer treatment.

PPIP5K, a type of enzyme called a kinase, produces unique cellular metabolites called inositol pyrophosphates. The authors previously showed that colorectal cancer cells deficient in PPIP5K have reduced growth rate despite enhanced energy production. In this study, using high-resolution mass spectrometry and genetics, the authors demonstrated that in cancer cells, PPIP5K was critical to synthesizing nucleotides, which are universal building blocks of DNA and RNA. Absence of precursor materials to synthesize these fundamental biological units inhibits growth in PPIP5K-deficient cancer cells. Furthermore, PPIP5K kinase activity, which synthesizes inositol pyrophosphates, is critical for nucleotide synthesis and cancer cell growth.

In addition, the authors determined two specific pathways of nucleotide synthesis that are regulated by PPIP5K the serine-glycine one-carbon pathway and the pentose phosphate pathway. These results provide insight on how a single metabolic enzyme can have an overarching impact on multiple metabolic processes during tumor development. (PR)

Citation:Gu C, Liu J, Liu X, Zhang H, Luo J, Wang H, Locasale JW, Shears SB. 2021. Metabolic supervision by PPIP5K, an inositol pyrophosphate kinase-phosphatase, controls proliferation of the HCT116 tumor cell line. Proc Natl Acad Sci U S A 118(10):e2020187118.

A team of NIEHS researchers found that breast cancer relative risk increases for women near the age that an older sister was previously diagnosed with breast cancer. This study was the first to model an age-time-dependent risk for a woman based on her proximity to a siblings age of breast cancer onset.

For this study, researchers used data from the NIEHS Sister Study, which examines familial and environmental risk factors for breast cancer and other diseases in women in the United States and Puerto Rico. The cohort of participants included more than 20,000 women who had one older sister previously diagnosed with breast cancer. Researchers employed several statistical models and methods to assess the pattern of risk over time for these women as they approached and passed their sisters age of diagnosis. The risk increased by 80% when the participant reached the sisters age of diagnosis. This familial clustering indicates there could be important genetic and early environmental factors that contribute to the timing of breast cancer onset. The findings have implications for patient counseling and personalized cancer screening. (VP)

Citation:Von Holle A, O'Brien KM, Sandler DP, Weinberg CR. 2021. Evidence for familial clustering in breast cancer age of onset. Int J Epidemiol 50(1):97104.

(Nicholas Alagna is an Intramural Research Training Award [IRTA] postbaccalaureate fellow in the NIEHS Mechanisms of Mutation Group. Victoria Placentra is an IRTA postbaccalaureate fellow in the NIEHS Mutagenesis and DNA Repair Regulation Group. Prashant Rai, Ph.D., is a visiting fellow in the NIEHS Clinical Investigation of Host Defense Group. Janelle Weaver, Ph.D., is a contract writer for the NIEHS Office of Communications and Public Liaison. Qing Xu is a biologist in the NIEHS Metabolism, Genes, and Environment Group.)

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Environmental Factor - May 2021: Intramural Papers of the Month - Environmental Factor Newsletter

The whales teeth were what had caught molecular ecologist Eline Lorenzens attention. Of the 18 chompers lining the front of the skulls mouth, some were twisted, not unlike a narwhals tusk. But the 30-year-old specimen, hidden away in the basement of the Natural History Museum of Denmark at the University of Copenhagen, didnt have a tusk at all. When Lorenzen became director of the museum in 2015, she decided to examine the skull more closely. Working with a team of collaborators, she extracted genetic material and compared it with DNA from the teeth of narwhal and beluga specimens in the museum. The skull, it turned out, was the first-ever confirmed narluga, the son of a beluga dad and a narwhal mom.

A deeper dive into the history of the skull (it had been found fixed atop a hunters home) revealed that this animal may not have been the only one of its kind. The hunter said hed seen it with two other similar-looking whale creatures, and he, apparently, isnt the only one to have seen a narluga. In fact, they are common enough that natives of western Greenland have a word for the narwhal-beluga hybrid, itorsaq.

Because several narlugas have been spotted before, researchers suspect that the creatures may be fertile, and that some narlugas may be the product of two narluga parents rather than one beluga and one narwhal. That notion challenges naturalists traditional view of hybrids as the result of maladaptive crossings, such as when a female horse mates with a male donkey and gives birth to a sterile mule. If the hybrids cant reproduce, they would seem to be irrelevant evolutionarily, but studies of the narluga and other naturally occurring hybrids have begun to hint that such offspring may not be the biological misfits they were once thought to be. They are not evolutionary dead-ends, and in some cases, may serve as evolutionary accelerators.

Were beginning to realize that hybridization exists in the evolutionary history of many organisms we didnt expect it to, including Homo sapiens, Scott Taylor, an evolutionary ecologist at the University of Colorado Boulder, tells The Scientist.

At some point in the past, black-tailed jackrabbits (Lepus californicus) and snowshoe hares (L. americanus) crossbred, with the hybrids mating again with snowshoe hares. A combination of whole-genome and whole-exome sequencing revealed that the resultant hares retained a variation of the Agouti gene that led to brown, rather than white, coat color in hare populations experiencing mild, less snowy winters, allowing them to better blend into the drab surroundings of dirt and dead leaves.

As far back as the 1930s, botanists realized that hybridization plays a role in the evolution of plant species. In 1938, Edgar Anderson and Leslie Hubricht laid out the idea of introgression to describe the hybridization of species of herbaceous perennial wildflowers of the Tradescantiagenus. The crosses led to offspring with an even split of parental genetic material, and typically those offspring then repeatedly bred with one of the original parent species, while still retaining genetic material from the other parent species. Alternatively, hybrids bred with other hybrids, and, eventually, entirely new plant species would emerge.

Zoologists knew about these and other examples of hybridization in the plant world, but there was a perception, Taylor says, that cross-species breeding was much less common in animals. That idea stemmed from biologist Ernst Mayrs description in the 1940s of the biological characteristics that defined speciesessentially, any animal population that could not or did not breed with other, similar populations. For more than two decades, including in his 1963 book Animal Species and Evolution, Mayr argued that the evolutionary importance of hybridization seems small in the better-known groups of animals. But the idea is not universally accepted, Taylor says. I dont know a lot of evolutionary biologists who study hybridization who adhere strictly to that concept.

Despite the dogma that hybrid animals in nature were rare and therefore not catalysts of evolutionary innovation, some biologists continued to study them, curious to uncover the barriers that prevented them from becoming new species, identify the new gene combinations created by hybridization, and understand how natural selection acted upon them. Focusing on animals in what scientists call hybrid zonesgeographical regions in which two species interbreed to produce offspring of mixed ancestryresearchers in the late 1980s and early 1990s began to show that, contrary to the prevailing viewpoint, hybridization was a valid mechanism of evolutionary changeone that could radically influence an animals ability to adapt to its environment.

A genetic analysis of a rare skull found at the Natural History Museum of Denmark showed that in the past few decades a male beluga (Delphinapterus leucas)and a female narwhal(Monodon monoceros) mated, creating a hybrid called a narluga that looked a bit like both. The animals 18 teeth were small, like a belugas, and twisted, like a narwhals tusk. Those teeth may have changed the way the narluga fed, not hunting on cod, squid, and shrimp in the water column as both of its parents did, but instead feeding off the bottom. Its teeth may have allowed it and others like it to occupy a different ecological niche than its parents.

Evidence for hybrid-driven adaptation is perhaps nowhere more profound than in the warm, tropical waters of Lake Victoria in Africa. There, more than 500 species of bony fishes called cichlids that sport brilliant orange, yellow, and blue hues, roam the lakes 2,400 cubic kilometers. Some species eat only plants, others eat invertebrates, the bigger species eat other fish, and still more feed on Lake Victorias detritus. Theres incredible diversity of species that live together in the same ecosystem, evolutionary ecologist Ole Seehausen of the University of Bern tells The Scientist. This struck me as a beautiful system, the interaction between ecology and evolution . . . to study speciation.

When Seehausen began to study the lakes cichlids roughly 30 years ago, it wasnt clear how the hundreds of species there had evolved. They werent geographically isolated, a common driver of speciation. Rather, the fish were all living in the same lake and could interact, yet there was still incredible cichlid diversity. Something else appeared to be driving their speciation.

With continued observation, Seehausen and others found that the barriers preventing the species in the lakes from mating were rather shallow, with some of the major ones being behavioral in nature. Males, for example, were defending their territories from males of both the same and other species, or females were choosing flashing mates of only their own species. That last barrier, based on color signaling, began to break down, Seehausen says, when the clarity of the water diminished in the 1990s, a result of wastewater from farms and other human activities polluting the lake. It turns out that when you change the visual signaling, and the perception of those signals, then not much more is needed to break down reproductive isolation, so many species then hybridize, Seehausen says.

Something similar appears to have happened thousands of years ago in Lake Victoria. Genetic analyses of the cichlids have revealed that their vast diversity can be traced back to a hybridization of two divergent lineages around 150,000 years ago. And Lake Victoria wasnt the only body of water in the region where hybridization appeared to play an important role in speciation. Further investigation revealed that cross-species mating had happened and continued to occur in nearby lakes, where it was driving cichlid diversity. This was replicated in several different lakes across Africa, Seehausen says.

As scientists began to look for other examples of hybridization in the wild, both past and present, they were not disappointed. Genetic analyses have revealed crosses between coyotes and gray wolves, polar bears and brown bears, chimpanzees and bonobos, finches in the Galapagos Islands, fish called sculpin, and even modern humans and Neanderthals.

Researchers suspect that hybridization events are perhaps becoming more common, as human disturbances shift species ranges in ways that promote breeding across similar species. In Colorado, for example, two varieties of small, nonmigratory birdsblack-capped chickadees and mountain chickadeeshave recently hybridized in areas being heavily developed by humans. If you look at the map and squint, the places theyre hybridizing seems to correlate nicely with places that humans have modified, whether thats the front range of the Rocky Mountains or Albuquerque, New Mexico, he says. His team hypothesizes that the species, which split some 1.5 million years ago, breed with each other in modified habitats because a resource needed by both, either breeding grounds or certain food sources, is bringing the birds together.

On occasion, a mountain chickadee (above) may mate with a black-capped chickadee.

Robert Taylor

Climate change may also be driving hybridization between species. Evolutionary biologists have seen pulses of cross-breeding as species shift where they live to higher or lower latitudes or altitudes to find cooler temperatures. When they move into those regions, the barriers to hybridization, such as differences in mate choice or other factors, might disappear. There are definitely compelling examples of climate change or environmental shifts influencing hybridization, says Molly Schumer, an evolutionary biologist at Stanford University, and my suspicion is its pretty widespread.

Obviously not all cases of hybridization involved the equal swapping of genes to form a completely new creature, as appeared to often happen with the cichlids, but in just the last few years, the consensus has been that hybridization in animals in particular is hugely widespread and much more common than was appreciated, Schumer says. The question in the field now, she says, is if this gene swapping is common, what is it doing?

When the waters in Lake Victoria in Africa became increasingly murky in the 1990s after mineral and farm runoff levels increased, two species of cichlids(Haplochromis nyererei and Neochromis sp. Bihiru scraper) no longer selectively mated with conspecifics, whom they had previously identified based on color. They hybridized readily, and others in the lake did too, creating new species, some of which have pervaded the altered ecological niches and adapted to them better than their parent species have.

In the case of cichlid hybrids, Seehausen found that not only did the hybrids have similar developmental and reproductive rates to non-hybrids, in some ways individuals with a genetic mishmash of two distinct species created were actually more suited to a particular environment or food source than their parents were.

A few years ago, Joana Meier, an evolutionary genomicist at the University of Cambridge who did her graduate work and a postdoctoral stint with Seehausen, delved into the genetics of the cichlids and spotted one type of hybrid that caught her attention: dwarf species that combine the body shape of a plant-eating species with the predatory habits of a bigger species that dines on other fish. Genetically, theyre like a mix of both, she says. In some cases, they have higher fitness [than either parent species] in different ecological niches. Seehausen has also shown this in the lab, creating hybrids that dont thrive on the food the parent species ate, but gobble down a new type of food and begin to flourish.

Schumer is seeing something similar in the hybridization of two related species of swordtail fish, Xiphophorus malinche and X. birchmanni. The fish live in the rivers of the Mexican state of Hidalgo and have begun hybridizing within the last 50 to 100 generations, probably as a result of some human disturbance to the river, she explains. The fish rely on their sense of smell and the signals in those scents to choose mates, but the contaminants in the rivers appear to be blocking the fish from picking out their own species, Schumer says, so theyve ended up mating across species boundaries. It turns out, that the mix-up could be helping both species survive by boosting genetic diversity.

Different species of swordtail fish, including Xiphophorus birchmanni (left) and X. malinche (top), can interbreed to form hybrid offspring (bottom).

DAN POWELL

Swordtail cross-breeding is really, really recent and gives us a good snapshot to [see] whats happening right after hybridization, Schumer says. Her genetic studies, along with those from other researchers investigating recent hybridization events, seem to show that right after these crosses occur, the genome of the hybrid undergoes incredible reorganization. Theres a lot of purging of deleterious alleles and rapid evolution happening right after you collide these two divergent genomes. The original swordtail parent species are closely related, differing by only 0.5 percent in their genetic makeup, Schumers studies show. Still, that small bit of genetic variation leads to substantial shifts in the species tolerances to cold, adaptation to elevation, and even an extra-long fin extension, called the sword, seen on X. birchmannibut not onX. malinche.

On the flip side, mushing together the two swordtail species genomes can cause issues in the offspring, with many not being able to reproduce. The combination of genes can even cause the hybrids to develop tumorous melanoma, which the parents dont. One of the biggest questions in the field, Schumer says, is: In this really rapid genome evolution happening after hybridization, how are all of these mechanismspositive effects of hybridization, negative effects of hybridization, interactions with the environment, social interactionsplaying out?

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Hybrid Animals Are Not Natures Misfits - The Scientist