It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Friday, October 13, 2023
CRYPTOZOOLOGY
Officially extinct fish is alive and well, according to DNA analyses
"Extinct" houting from the collection of the Natural History Museum London. Credit: Ymke Winkel
The houting, a fish species that lived in North Sea estuaries and is officially extinct, turns out to be alive and well. Researchers from the University of Amsterdam and the Natural History Museum London extracted DNA from multiple houtings conserved in the museum, up to 250+ years old. Next they compared the DNA of these museum fish with DNA from various currently occurring sibling species. The biologists found hardly any genetic difference between houting and a species called European whitefish. Since this species is still common, houting therefore isn't extinct.
In a recent publication in the journal BMC Ecology and Evolution, the researchers describe how they isolated mitochondrial DNA from the fish. They even managed to obtain a small piece of DNA from a dried North Sea houting from 1754 that was used by Linnaeus for the official species description. Next they used the DNA to create a phylogenetic tree, in which all examined houting (Coregonus oxyrinchus) ended up in the same group as the European whitefish (Coregonus lavaretus).
Not extinct
According to the researchers, houting is therefore not a separate species. First author Rob Kroes of the University of Amsterdam says, "The European whitefish is fairly widespread in Western and Northern Europe, both in freshwater rivers and lakes, estuaries and the sea. Because we found no species difference between houting of the past and today's European whitefish, we do not consider the houting to be extinct."
So how is it possible that the houting was officially declared extinct in 2008? Kroes says, "It often happens that there is confusion as to whether animals are one species or not. Especially when fish are involved. They often have a lot of variation in morphological traits within a species. In this case, biologists long thought that houting is a different species from the European whitefish due to the length of the snout and the number of gill rakers. But these traits are simply not suitable to say that houting is a different species. Our DNA research now clearly shows that it isn't."
Name change
A change of the official Latin species name seems to be in order. However, a definitive adjustment of the name requires a bit of additional research on the DNA of the dried fish from 1754. According to the researchers, this will be difficult to do.
Kroes states, "The DNA is old and damaged, but I think we should try. At the moment, the protected status of various coregonids is a mess. According to the IUCN, North Sea houting is extinct; at the same time, there are various European nature laws that state that both houting and European whitefish must be protected. So we are actually protecting an extinct species that is just swimming around at the moment."
More information: R. Kroes et al, Phylogenetic analysis of museum specimens of houting Coregonus oxyrinchus shows the need for a revision of its extinct status, BMC Ecology and Evolution (2023). DOI: 10.1186/s12862-023-02161-7
The Læborg Runestone, one of the Ravnunge-Tue Stones. Credit: Roberto Fortuna / CC BY-SA 4.0
Archaeologists have used 3D scanning to investigate inscriptions carved on two groups of Danish runestones, revealing that four stones were likely made in dedication to a powerful Viking Queen.
The first group, the Jelling Stones, were raised by Harald Bluetooth, the king who is credited with founding the Danish state, in commemoration of his parents Gorm and Thyra. The second group, the Ravnunge-Tue Stones, also mention a woman called Thyra.
The team theorized that these two groups of stones referred to the same person. If correct, then Thyra would be the most-mentioned person on Viking-Age Danish runestones.
"We wanted to see if we could find the same rune carver on some of these stones, so that we could connect the Ravnunge-Tue stones with the Jelling stones," says lead author of the research, Dr. Lisbeth M. Imer from the National Museum of Denmark. "If there was a connection, it would be highly likely that all the stones referred to the same woman, Thyra, mother of Harald Bluetooth."
To test the validity of this theory, Dr. Imer and a team of investigators from several Scandinavian institutions made 3D models of the runestones and analyzed the shape and carving techniques used to cut the runes and the language used. Their results are published in the journal Antiquity.
3D model of the Jelling 2 Stone, highlighting the runes analyzed. Credit: Antiquity (2023). DOI: 10.15184/aqy.2023.108
The authors compared carved grooves of well-preserved runestones in order to identify the distinctive marks made by different carvers. Similarities between the runes of the Læborg Stone (one of the Ravnunge-Tue Stones) and the Jelling 2 Stone suggest that they were engraved by the same person.
Therefore, the references to Thyra on both groups of stones likely refer to the same person—the Danish Queen and mother of Harald Bluetooth. This indicates that she was a particularly powerful and celebrated individual. It is likely that she held land and authority in her own right, not only through her husband.
"No other Viking man or woman in Denmark has been mentioned on that many runestones," says Dr. Imer, "and it underlines her undeniable importance for the assembling of the realm under the rule of her son, Harald Bluetooth."
Importantly, this means that women likely had more influence in Viking-Age Denmark than previously believed. It indicates that Viking women may have been able to hold power in their own right and rule on behalf of their husbands or under-age sons.
It also has important implications for our knowledge on the formation of the Danish state.
"The combination of the present analyses and the geographical distribution of the runestones indicates that Thyra was one of the key figures—or even the key figure—for the assembling of the Danish realm," state the authors.
More information: Lisbeth M. Imer et al, A lady of leadership: 3D-scanning of runestones in search of Queen Thyra and the Jelling Dynasty, Antiquity (2023). DOI: 10.15184/aqy.2023.108
ASV change, sea surface temperature, and mixed layer depth. a Mixed layer depth (MLD) difference (percent) between GW-ASVCTL and GW (GW-ASVCTL minus GW). The ASV kinetic energy (KE) difference is represented in black contour. The average GW MLD (m) is represented in red contour. b Sea surface temperature (SST) difference (°C) between GW-ASVCTL and GW. The ASV kinetic energy difference is represented in black contour. The average SST (°C) is represented in red contour. c Mixed layer depth (MLD) difference (percent) between GW-ASVCTL-FLX and GW. The MLD difference (percent) between GW-ASVCTL and GW is represented in contour. d Average SST difference (°C) between GW-ASVCTL-FLX and GW. The SST difference (°C) between GW-ASVCTL and GW is represented in contour. e, f The region 10°N–10°S (e) and 20°S–40°S (f) are considered. The mean MLD (m; abscissa) vs. KE ASV (m2 s−2; ordinate) vs. SST anomaly compared to GW-ASVCTL (color) for each experiment are represented. The black circle represents the experiment CTL, the black square GW, the green circle GW-ASVCTL, the green square GW-ASVCTL-FLX (the ASV value corresponding to GW-ASVCTL is plotted here), the blue triangle GW-ASVM10, the blue hexagon GW-ASVM20, the red triangle GW-ASVP10, and the red hexagon GW-ASVP20. Credit: npj Climate and Atmospheric Science (2023). DOI: 10.1038/s41612-023-00459-3
The strength of the wind has an important influence on ocean circulation. This is particularly true for extreme events such as storm fronts, tropical storms and cyclones. These weather patterns, which last from a few days to a few weeks, will change in the future due to climate change. In particular, the average energy input into the ocean from mid-latitude storms is expected to decrease, while equatorial regions will become more active. Scientists call these different weather patterns "Atmospheric Synoptic Variability" (ASV).
Two climate researchers—Dr. Olaf Duteil from the GEOMAR Helmholtz Center for Ocean Research Kiel and Professor Dr. Wonsun Park from the IBS Center for Climate Physics and Pusan National University, Korea—have now for the first time investigated the integrated effects of long-term changes in these weather patterns on the Pacific basin in a modeling study. The results show how important it is to take these changes into account in climate models. They have now published their findings in the journal npj Climate and Atmospheric Science.
From a climate point of view, the weather is usually considered as "noise" and is not systematically analyzed in long-term climate projections, say the two researchers. "However, it is not enough to look at average atmospheric properties, such as mean wind speeds, to understand the influence of climate change on the ocean," says Duteil, "it is crucial to consider the cumulative effect of short-term changes in weather patterns to get a complete picture."
The researchers expect that future changes in Atmospheric Synoptic Variability will affect the mixing of the ocean's layers, as a smaller or larger input of kinetic energy into the ocean due to weather phenomena will lead to less or more mixing, respectively. The researchers predict that the reduction in ASV in subtropical regions will lead to a shallowing of the mixing layer in the ocean, while it will become deeper at the equator as ASV increases
They also show that a future reduction in ASV decreases the strength of oceanic circulation systems—the so-called subtropical and tropical cells—and the large-scale ocean circulation. These systems connect mid-latitudes and equatorial latitudes via upper ocean pathways. They are driven by the trade winds north and south of the equator, regulate the upwelling of equatorial waters and play a fundamental role in determining the surface temperature of the oceans and thus primary productivity in the tropics.
This study highlights the need to better quantify ASV and weather patterns in climate models, as changes in ASV have a large impact on future upper ocean circulation and mean properties. Duteil states, "This quantification should be used to improve our confidence in projections of future climate, especially when analyzing large ensembles of climate models."
More information: Olaf Duteil et al, Future changes in atmospheric synoptic variability slow down ocean circulation and decrease primary productivity in the tropical Pacific Ocean, npj Climate and Atmospheric Science (2023).
Researchers prepare a rosette sampler for deployment as part of the GEOTRACES program to study cobalt and other trace elements in the ocean. Credit: Bill Schmoker, PolarTREC.
As the climate warms, there is major concern that Earth's ocean will lose oxygen. A study published in Geophysical Research Letters by oceanographers at the University of Hawai'i at Mānoa revealed that locked in ancient deep-sea sediments is evidence for oxygen loss in the world's ocean during past glacial periods, indicating that widespread oxygen loss with current climate change may not be permanent.
Scientists first measured oxygen in the oceans in the 1960s. Since then, they have observed decreasing levels in the mid-depths of the ocean—a phenomenon that can be explained in part by the fact that warmer waters hold less oxygen. Less oxygen in the water can lead to habitat loss for fish and other marine species that need oxygen to breathe. If the naturally-occurring low-oxygen regions in the Eastern Pacific expand in a warmer climate, Pacific Island fisheries could be significantly impacted.
Cobalt holds the clues in deep-sea sediments
"Ultimately, it would be helpful if we knew how low-oxygen regions of the ocean changed with past climate changes," said Nick Hawco, lead author of the study and assistant professor of oceanography, in the UH Mānoa School of Ocean and Earth Science and Technology (SOEST).
"However, the problem is that oxygen is a gas, so we don't have any reservoirs of past oceans to test the oxygen content. Our new study builds off of prior work where we discovered that low oxygen water bodies in the Pacific are enriched in the metal cobalt."
"One of the biggest sources of cobalt to the oceans is where oxygen deficient zones intersect with the continental shelf, leach cobalt from the shelf, and then transport it across the ocean in a plume of low oxygen water," said Rhea Foreman, study co-author and oceanography researcher in SOEST. "The cobalt is subsequently incorporated into minerals that are deposited onto the seafloor and preserved in the sedimentary record."
Deep sea sediments revealed ocean conditions from the past 145,000 years. Credit: Rhea Foreman/ UHM—SOEST
The researchers analyzed seafloor sediments from the past 145,000 years, a timeframe that includes the last major ice age. They found more cobalt in sediments from the past ice ages, compared to more recent sediments.
"This means that there was a build up of cobalt in the Pacific during the last ice age," said Hawco. "Because high cobalt is a proxy, or a stand-in, for low oxygen, this indicates there were probably larger regions of low oxygen waters in the Pacific during that time."
Time to adapt
One suggested explanation for low-oxygen waters being more common in cold climates is the change in ocean circulation that accompanies climate change. Today, complex currents flowing from west to east help add oxygen to the mid-depth waters of the tropical Pacific.
"If these currents weaken, the oxygen in the Pacific would decline," said Hawco. "This is what we think happened during the last glacial period. But we don't know how strongly—or how fast—these currents will respond to ocean warming."
This could mean that fish and other species are able to adapt to changing oxygen as long as these changes are slow enough, as appears to have happened in the past.
"We need to reduce emissions as soon as possible to buy time for these ecosystems to adapt to the climate change we are already locked into based on the last 150 years of carbon emissions," added Hawco.
More information: Nicholas J. Hawco et al, Expansion of Ocean Anoxia During Glacial Periods Recorded in the Cobalt Flux to Pelagic Sediments, Geophysical Research Letters (2023). DOI: 10.1029/2023GL105135
Neanderthal reconnstruction made by brother Kennis for Neanderthal Museum. Credit: Neanderthal Museum
The fact that Neanderthals were able to make a fire and use it, among other things, for cooking, demonstrates their intelligence. "This confirms our observations and theories from previous studies," explains Diego Angelucci, archaeologist at the University of Trento and co-author of the study.
"Neanderthals were capable of symbolic thought, could create artistic objects, knew how to decorate their bodies using personal ornaments and had an extremely varied diet. Add to that that, based on our findings, we can say with certainty that they habitually ate cooked food. This ability confirms that they were as skilled as the Homo sapiens who lived millennia later."
But how did we learn that Neanderthals knew how to use fire? "There is a general agreement among archaeologists that they knew how to use fire. However, one thing is to use fire started by natural processes, such as lightning, another is to make it, feed it with wood and use it for cooking, heating and defense. In this study we demonstrate that there is no doubt that Neanderthals could make a fire and that fire was a central element in their daily life."
The article "Formation processes, fire use, and patterns of human occupation across the Middle Paleolithic of Gruta da Oliveira" was published October 11 in PLOS ONE.
Excavation in the Gruta de Oliveira. Credit: João Zilhão
Twenty years of excavations
The article documents and compares the remains of structured fires found in the same location: The Gruta de Oliveira in central Portugal, one of the most important European archaeological sites for the Middle Paleolithic. What is so exceptional about this cave is that excavations were conducted systematically and with great accuracy for more than 20 years between 1989 and 2012.
The works were led by an international group of archaeologists supervised by João Zilhão (University of Lisbon), who authored the study together with Diego Angelucci (UniTrento) and Mariana Nabais (IPHES, Catalan Institute for Human Paleoecology and Social Evolution, Tarragona).
Gruta de Oliveira. Credit: João Zilhão
The cave is part of the Almonda karst system, a vast network of caves placed at different elevations above a large spring that have been inhabited in different periods during Prehistory. The oldest layers of the Gruta de Oliveira, which includes a number of passages, date back to about 120,000 years ago, the most recent to about 40,000: It is believed that Neanderthals inhabited this place between 100,000 and 70,000 years ago.
"For us, Almonda is a gift that keeps on giving for the variety and quantity of artifacts and remains that we have found over the years: from the remains dating back to the Lower Paleolithic to the chipped stones of the Mousterian culture, there is really everything," Angelucci comments.
Hearths and food remains
In this case however, what caught the attention of archaeologists were the traces of hearths intentionally built and used in the cave. The archaeologists found about a dozen hearths at various stratigraphic levels in an excavation area of about 30 square meters and six meters deep. The unmistakable basin-like, circular structures were filled with remains.
Findings from inside and near the hearths demonstrate that the inhabitants of the caves used to cook their food. "We found burnt bones, burnt wood and ash remains. And the rock underneath—continues Angelucci—has been reddened by the heat: This is a crucial detail because it tells us that the structure is in a primary position. And it has always been there. Fire is a fundamental element in their daily lives. It makes the place comfortable and helps socialization. It gives back that basic idea of 'home' that perhaps could also apply to them."
Excavation in the Gruta de Oliveira. Credit: João Zilhão
A varied diet
What did Neanderthals eat? "We were able to find out what they ate and even the cooking techniques they used. We found the remains and burnt bones of cooked goats, deer, horses, aurochs (extinct bulls), rhinos, turtles, which were probably laid on their carapace and stewed on hot stones."
"Meat was on the menu in this inland cave, but in other excavations in caves overlooking the western Mediterranean Sea near Cartagena (Spain), remains of fish, mussels and mollusks, even roasted pine nuts, were found. We had already demonstrated in 2020 in another paper that appeared in Science that Neanderthals had a varied diet, but the Portuguese excavations have further confirmed that they used fire to cook food."
Despite the excavations, the archaeologists were not able to determine how the Neanderthals started a fire.
"Perhaps they did as in Neolithic times, striking flint rocks against another rock to throw sparks on a tinder, such as a dry nest for example. This is a prehistoric technique that was discovered by studying Ötzi, the Ice man. So far however, we have found no evidence of this."
Excavating a series of layers that cover 30,000 years, however, gave archaeologists the opportunity to compare the data with other sites in the same area that date back to Upper Paleolithic and involve a more recent period, where Homo sapiens were confirmed in the area. "We found no difference: they lived in the caves in similar ways. Their skills are also a sign of intelligence. They did not belong to different species, I would say that they were different human forms."
The study
This article represents the end of a long data analysis work that examined 30 years of findings. The Portuguese team of João Zilhão studied the stone tools, while Mariana Nabais analyzed the bone remains and conducted spatial analyses to examine the position of the finds in the cave and the location of the fires.
The research group of the University of Trento (Department of Humanities) focused on stratigraphy and microscopic studies. "We relied on the techniques of interdisciplinary archaeology: preliminary on site studies, meticulous excavation, accurate positioning of all the finds, systematic sieving, the precise method of collecting data in the field, the collection of samples for subsequent analysis under the microscope or in the laboratory: this type of archaeology is carried out with the most advanced methodologies. They require time and resources and this is what we teach our students."
More information: Diego E. Angelucci et al, Formation processes, fire use, and patterns of human occupation across the Middle Palaeolithic (MIS 5a-5b) of Gruta da Oliveira (Almonda karst system, Torres Novas, Portugal), PLOS ONE (2023). DOI: 10.1371/journal.pone.0292075
Reexamination of ancient jawbone found in Ethiopia concludes it came from Homo erectus infant
by Bob Yirka , Phys.org
The GAR IVE mandible. Credit: Science (2023). DOI: 10.1126/science.add9115
An international team of geoscientists, archaeologists and anthropologists has found evidence that strongly suggests an infant jawbone found in the Ethiopian highlands came from a Homo erectus child. In their study, reported in the journal Science, the group conducted multiple tests to learn the true nature of the fossil.
The jawbone was first uncovered back in 1981 at the Garba IV dig site in the Ethiopian highlands by a different team of researchers—it was subsequently nicknamed Little Garba. Over the years, several groups have tested the fossil to learn the species of the individual. No clear consensus was established, but it was found to be a member of the genus Homo.
To pinpoint the species, the researchers on this new effort applied synchrotron imaging to the teeth and compared those images with those of other hominin species. This showed the closest match to be Homo erectus.
Prior research had shown that the layers of sediment in which the jawbone was found were approximately 2 million years old, suggesting that Little Garba lived approximately 2 million years ago, making the jawbone one of the oldest known Homo erectus fossils ever found.
The research team then turned their attention to the stone tools found at the same level at the dig site. They found what they describe as a transition from Oldowan tools to Acheulean tools, which were more advanced. Prior research had shown that such tools were developed approximately 2 million years ago, coinciding with the age of Little Garba.
The researchers conclude that the evidence found at the Garba IV site suggests that once Homo erectus populations arrived in the highlands, they had to adapt to both the thinner air (Garba IV sits at 2,000 meters above sea level) and geographical conditions. That included improving their tools and weapons, which would allow them not only to take down prey found in the area, but to process it for use as food and materials for keeping warm in the cooler highlands.
More information: Margherita Mussi et al, Early Homo erectus lived at high altitudes and produced both Oldowan and Acheulean tools, Science (2023). DOI: 10.1126/science.add9115
Canadian cannabis legalization linked to increased and decreased hospitalization, depending on the province
by Justin Jackson , Medical Xpress
Age and sex standardized rate of hospitalizations due to cannabis per 100 000 individuals and per 1000 all-cause hospital admissions between January 2015 and March 2021. Shaded regions indicate 95% CIs. Credit: JAMA Network Open(2023). DOI: 10.1001/jamanetworkopen.2023.36113
Research led by the Bruyère Research Institute, Canada, has looked into cannabis-related hospitalization rates before and after cannabis legalization in Canada.
In a paper, "Changes in Cannabis-Attributable Hospitalizations Following Nonmedical Cannabis Legalization in Canada," published in JAMA Network Open, the team finds links between rapid commercialization and the COVID-19 pandemic.
The study found 105,203 hospitalizations due to cannabis in Canada's four most populous provinces of Ontario, Quebec, Alberta, and British Columbia, covering the period from January 2015 to March 2021. The most significant relative increase in hospitalizations was for cannabis-induced psychosis.
Legalization with restrictions was associated with a gradual decrease in hospitalizations due to cannabis. The later rise of stores, cannabis products and the COVID-19 pandemic were associated with a sharp increase in cannabis-related hospitalization, with the exception of British Columbia, where rates dropped.
British Columbia, which comprised 25% of study participants, experienced a 10% reduction in hospitalization events after complete legalization and commercialization compared to pre-legalization rates.
Quebec, on the other hand, at 44% of study participants, was the slowest to allow commercialization and maintained stricter limitations on the types of products that could be sold, yet showed a 37% increase in hospitalization after complete legalization and commercialization compared to pre-legalization rates. Alberta showed an 18% increase, and Ontario was at 20%.
The findings suggest that the initial period following legalization in Canada, with tightly controlled products and limited store access, was not associated with increased hospitalizations due to cannabis. Hospitalizations increased sharply following widespread commercialization in some provinces and decreased in other areas.
Associations were seen between expanded access and increased cannabis hospitalizations, particularly for cannabis-induced psychosis. The unfortunate overlap of store and product expansion and the COVID-19 pandemic challenge the explicit attribution of increases to cannabis access alone.
Canada legalized the sale of cannabis in October 2018, with each province and territory creating its own regulations regarding how cannabis would be sold and the types of products that could be allowed. Initially, all provinces in Canada were only allowed to sell dried cannabis.
In October 2019, cannabis producers were allowed to apply to begin selling new high-potency cannabis products, including edibles, vape pens, and concentrates. Most provinces, other than Quebec, allowed these products to come to market starting in early 2020.
Provinces also took differing approaches to cannabis retail store access. Alberta had a rapid expansion of stores and legal sales immediately following legalization. In contrast, Ontario and British Columbia initially had very low cannabis sales and store access, followed by rapid growth beginning in early 2020. Quebec had the lowest per capita stores and sales throughout the study despite having the highest hospitalization increase from start to finish.
The different approaches to legalization allowed the researchers an opportunity to explore how different regulatory approaches to cannabis markets impact the overall burden on public health. Unfortunately, a study related to hospitalization rates that has a pandemic walk through the middle of the critical data collection period has an unavoidable confounding bias.
COVID-19 pandemic aside, other limitations exist in finding associations between legalization stages and hospital visits. One is that the three-year pre-legalization period (2015–2018) already showed a significantly increased trend in cannabis-related hospitalization rates. That trend, provided in the study, appears to have been slowed by legalization.
Another factor is that patients may simply be more likely to seek medical help and disclose cannabis use after legalization when there is less stigma and no fear of criminal prosecution.
More information: Daniel T. Myran et al, Changes in Cannabis-Attributable Hospitalizations Following Nonmedical Cannabis Legalization in Canada, JAMA Network Open (2023). DOI: 10.1001/jamanetworkopen.2023.36113
A diverse set of species, from snails to algae to amoebas, make programmable DNA-cutting enzymes called Fanzors—and a new study from scientists at MIT's McGovern Institute for Brain Research has identified thousands of them. Fanzors are RNA-guided enzymes that can be programmed to cut DNA at specific sites, much like the bacterial enzymes that power the widely used gene-editing system known as CRISPR. The newly recognized diversity of natural Fanzor enzymes, reported Sept. 27 in the journal Science Advances, gives scientists an extensive set of programmable enzymes that might be adapted into new tools for research or medicine.
"RNA-guided biology is what lets you make programmable tools that are really easy to use. So the more we can find, the better," says McGovern Fellow Omar Abudayyeh, who led the research with McGovern Fellow Jonathan Gootenberg.
CRISPR, an ancient bacterial defense system, has made it clear how useful RNA-guided enzymes can be when they are adapted for use in the lab. CRISPR-based genome editing tools developed by MIT professor and McGovern investigator Feng Zhang, Abudayyeh, Gootenberg, and others have changed the way scientists modify DNA, accelerating research and enabling the development of many experimental gene therapies.
Researchers have since uncovered other RNA-guide enzymes throughout the bacterial world, many with features that make them valuable in the lab. The discovery of Fanzors, whose ability to cut DNA in an RNA-guided manner was reported by Zhang's group earlier this year, opens a new frontier of RNA-guided biology. Fanzors were the first such enzymes to be found in eukaryotic organisms—a wide group of lifeforms, including plants, animals, and fungi, defined by the membrane-bound nucleus that holds each cell's genetic material. (Bacteria, which lack nuclei, belong to a group known as prokaryotes.)
"People have been searching for interesting tools in prokaryotic systems for a long time, and I think that that has been incredibly fruitful," says Gootenberg. "Eukaryotic systems are really just a whole new kind of playground to work in."
One hope, Abudayyeh and Gootenberg say, is that enzymes that naturally evolved in eukaryotic organisms might be better suited to function safely and efficiently in the cells of other eukaryotic organisms, including humans. Zhang's group has shown that Fanzor enzymes can be engineered to precisely cut specific DNA sequences in human cells. In the new work, Abudayyeh and Gootenberg discovered that some Fanzors can target DNA sequences in human cells even without optimization. "The fact that they work quite efficiently in mammalian cells was really fantastic to see," Gootenberg says.
Prior to the current study, hundreds of Fanzors had been found among eukaryotic organisms. Through an extensive search of genetic databases led by lab member Justin Lim, Gootenberg and Abudayyeh's team has now expanded the known diversity of these enzymes by an order of magnitude.
Among the more than 3,600 Fanzors that the team found in eukaryotes and the viruses that infect them, the researchers were able to identify five different families of the enzymes. By comparing these enzymes' precise makeup, they found evidence of a long evolutionary history.
Fanzors likely evolved from RNA-guided DNA-cutting bacterial enzymes called TnpBs. In fact, it was Fanzors' genetic similarities to these bacterial enzymes that first caught the attention of both Zhang's group and Gootenberg and Abudayyeh's team.
The evolutionary connections that Gootenberg and Abudayyeh traced suggest that these bacterial predecessors of Fanzors probably entered eukaryotic cells, initiating their evolution, more than once. Some were likely transmitted by viruses, while others may have been introduced by symbiotic bacteria. The research also suggests that after they were taken up by eukaryotes, the enzymes evolved features suited to their new environment, such as a signal that allows them to enter a cell nucleus, where they have access to DNA.
Through genetic and biochemical experiments led by biological engineering graduate student Kaiyi Jiang, the team determined that Fanzors have evolved a DNA-cutting active site that is distinct from that of their bacterial predecessors. This seems to allow the enzyme to cut its target sequence more precisely the ancestors of TnpB, when targeted to a sequence of DNA in a test tube, become activated and cut other sequences in the tube; Fanzors lack this promiscuous activity. When they used an RNA guide to direct the enzymes to cut specific sites in the genome of human cells, they found that certain Fanzors were able to cut these target sequences with about 10 to 20 percent efficiency.
With further research, Abudayyeh and Gootenberg hope that a variety of sophisticated genome editing tools can be developed from Fanzors. "It's a new platform, and they have many capabilities," says Gootenberg.
"Opening up the whole eukaryotic world to these types of RNA-guided systems is going to give us a lot to work on," Abudayyeh adds.
More information: Kaiyi Jiang et al, Programmable RNA-guided DNA endonucleases are widespread in eukaryotes and their viruses, Science Advances (2023). DOI: 10.1126/sciadv.adk0171
