Confined to a single deep limestone cave in Nevada’s Mojave Desert, 263 of them live in water that hovers around 93 degrees Fahrenheit year-round, with food resources so scarce that they are always on the edge of starvation, and with oxygen levels so low that most other fish would die immediately. The pupfish, Cyprinodon diabolis, live in the smallest habitat of any known vertebrate.

New research now documents the extreme effect that these harsh and isolated conditions have had on this fish’s genetic diversity.

In a paper published this week in the journal Proceedings of the Royal Society B, University of California, Berkeley, biologists report the first complete genome sequences of eight pupfish species from the American Southwest — 30 individuals in all, including eight Devils Hole pupfish. Astoundingly, the Devils Hole pupfish is so inbred that 58% of the genomes of these eight individuals are identical, on average.

“High levels of inbreeding are associated with a higher risk of extinction, and the inbreeding in the Devils Hole pupfish is equal to or more severe than levels reported so far in other isolated natural populations, such as the Isle Royale wolves in Michigan, mountain gorillas in Africa and Indian tigers,” said lead researcher Christopher Martin, UC Berkeley associate professor of integrative biology and curator of ichthyology in the campus’s Museum of Vertebrate Zoology. “Although we were not able to directly measure fitness, the increased inbreeding in these pupfish likely results in a substantial reduction in fitness.”

Other pupfish species are also inbred, the researchers found, but only between 10% and 30% of their genomes are identical.

Graduate student David Tian, lead author of the study, said that the level of inbreeding in the Devils Hole pupfish is equivalent to what would happen if four to five generations of siblings mated with one another. This tends to burn in or fix, rather than weed out, harmful mutations, potentially dooming a population to extinction by mutational meltdown. The Devils Hole pupfish species is currently doing well in the wild and in captive or “refuge” populations, but such low genetic diversity could spell trouble as the climate changes and human impacts become greater.

In the face of these potential threats, the new genome sequences will help scientists and conservationists assess the health of native pupfish populations and potentially intervene in refuge populations to increase the genetic diversity of these species — the Devils Hole pupfish, in particular.

“With this new genomic data, there’s a lot of potential to look not just at genetic diversity and how these species are related to each other phylogenetically, but also look at inbreeding and mutation load to get an idea of what their current status is, how evolutionary history may have influenced their current genetic variation, and think about where the population is going and what we should do, if anything, to preserve these species,” Tian said.

Population decline and rescue

Pupfish species are scattered around the globe and tend to like isolated lakes and springs, often with extreme conditions that most fish would find unsurvivable. About 30 species inhabit warm, salty desert springs and streams in California and Nevada. Martin has studied various pupfish populations, including several on San Salvador Island in the Bahamas, to understand the genetics behind their adaptation to extreme conditions and unusual ecological niches.

The Devils Hole pupfish, however, is unique in its small range and perilous existence, Martin said, making its fluctuating population in the wild worrisome to conservationists.

“Part of the question about these declines is whether they may be due to the genetic health of the population,” Martin said. “Maybe the declines are because there are harmful mutations that have become fixed because the population is so small.”

The small population is partly a result of human incursions into their habitat, Martin noted. Local ranchers and developers pumped groundwater in the region in the 1960s and ’70s that drastically reduced the water level in Devils Hole, leading to a drop in population levels. A 1976 Supreme Court ruling that allowed the federal government to limit groundwater pumping saved Devils Hole and the resident population, while captive breeding at a nearby 100,000-gallon pool in the Ash Meadows National Wildlife Refuge rescued the species. Nevertheless, a decline in the 1990s led the wild population to its nadir in 2013: 35 individuals. The wild population has since recovered, while the refuge population has ballooned to about 400, twice the wild population.

Humans are not totally to blame for the lack of genetic diversity in the Devils Hole pupfish, however. The UC Berkeley researchers also sequenced the genome of a pupfish collected in 1980 and held at the University of Michigan. It showed inbreeding and a lack of genetic diversity similar to that found in individuals collected recently, most of which died a natural death. This implies that the pupfish has likely seen population bottlenecks frequently over hundreds, if not thousands, of years.

One result of this, Martin and Tian found, is that 15 genes have disappeared entirely from the Devils Hole pupfish genome. Five of them seem to be involved in adaptation to living in low-oxygen or hypoxic environments.

“These deletions are a paradox, because this is a habitat where you’re most exposed to hypoxia,” Martin said. “It could have something to do with the stability of the habitat over time. But it looks to us like the hypoxia pathway is broken. Once you break one gene, it doesn’t really matter if you break additional genes in that regulatory pathway. Our future work is to actually look at what these deletions do. Do they increase tolerance of hypoxia? Do they decrease tolerance of hypoxia? I think those two scenarios are equally plausible at this time.”

Selective breeding within a captive population of Devils Hole pupfish could help increase the diversity and perhaps save the species from eventual extinction, he said. And to restore genes already lost, CRISPR genome editing could add them back.

The fact that the genome of the fish collected in 1980 was about as inbred as today’s fish is “maybe good news,” Martin said, “in that the population has historically been highly inbred with very low genetic diversity, suggesting that the recent decline in the ’90s, with population bottlenecks to only 35 fish in 2013 and 38 fish in 2007, doesn’t seem to have had much of an effect.”

Tian is currently analyzing about 150 complete genome sequences of nine species of American pupfish to get a more complete picture of the deleterious mutations and gene deletions in the various Southwestern populations. He sees the study as an example of what conservation genomics can do for endangered and possibly inbred populations around the world.

“We’re on a really cool cusp when it comes to using genomic data and applying it to conservation, especially at a time where it’s a problem that is likely only going to get worse with climate change and increased habitat fragmentation and just anthropogenic changes,” he said.

Tian is leery of genetic interventions, however, since little is known about how genes influence the physical and behavioral characteristics of a species and how this relates to fitness and adaptation to a specific environment. Conservation should still be a priority.

“The answer is still increased funding for these populations, protecting habitats, legal avenues for protecting these species and figuring out ways for humans and these endangered species to coexist on this planet,” he said.

Co-authors with Martin and Tian are Austin Patton of UC Berkeley and Bruce Turner of Virginia Tech in Blacksburg. The work is funded by the U.S. Fish and Wildlife Service, National Park Service, National Science Foundation (1749764) and National Institutes of Health (5R01DE027052-02).

New findings from a meta-analysis published in Nature Immunology examine the biological mechanisms responsible for why some people’s immune systems respond differently to vaccinations, which could have global implications for the development and administration of vaccines.

As part of a series of studies for The Human Immunology Project Consortium (HIPC), a network of national research institutions studying the range of responses to different infections and vaccinations, Emory researchers analyzed the molecular characteristics of 820 healthy young adults who were immunized with 13 different vaccines to identify specific biomarkers that generate antibody response to vaccines.

The participants were separated into three endotypes, or groups with a common gene expression, based on the level of inflammatory response prior to vaccination — a high inflammatory group, a low inflammatory group, and a mid-inflammatory group. After studying the immunological changes that occurred in participants following vaccination, researchers found the group that had the highest levels of inflammation prior to vaccine had the strongest antibody response.

“We were surprised because inflammation is usually depicted as something that is bad,” says Slim Fourati, PhD, bioinformatic research associate at Emory University and first author on the paper. “These data indicate that some types of inflammation can actually foster a stronger response from a vaccine.”

Fourati, Dr. Rafick-Pierre Sekaly, professor and senior author of the paper, and the HIPC team identified specific biomarkers among this group and cellular features that characterized the pre-vaccination inflammatory signature, information that can be used to predict how well an individual will respond to a vaccine.

“With the knowledge we now have about what characteristics of the immune system enable a more robust response, vaccines can be tailored to induce this response and maximize their effectiveness,” says Fourati. “But we still have more questions to answer.”

More research is needed to determine the cause of this inflammation in otherwise healthy adults. Additionally, Fourati suggests future studies should look at how these biomarkers facilitate vaccine protection in older age groups and among populations who are immunocompromised.

Published simultaneously with three other HIPC studies by researchers at Yale’s School of Medicine, Stanford University, University of Cincinnati, Harvard Medical School, and Columbia University Medical Center, these findings can serve to improve vaccine response across all individuals. Better understanding of how various pre-vaccine immune states impact antibody responses opens the possibility of altering these states in more vulnerable individuals. For example, scientists may give patients predicted to have a weaker immune response an adjuvant with the vaccine to trigger the inflammatory genes associated with greater protection.

This work will help enable improved, more efficient clinical trials for the development of new vaccines.

The HIPC program was established in 2010, renewed in 2015 and 2021, by the NIAID Division of Allergy, Immunology, and Transplantation.

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However, fecal microbial transplants have also been given to alter a recipient’s metabolism to reduce obesity or alter immunity to fight cancer, and in those transplants recipients are not given suppressive antibiotics to eliminate the microbial community prior to the transplant. In these cases, the initial gut community after transplant is a consortium of donor and recipient microbes that have to compete as new microbial strains are introduced into an established community.

University of Alabama at Birmingham researchers now report in the journal PLOS One that there is a lack of predictability for fecal microbial transplants to change the gut microbial community to correspond to that of the donor when there is no preconditioning to reduce the recipient microbe community. This contrasts with the C. difficile fecal microbial transplants after suppressive antibiotic therapy, where stable long-term colonization of donor strains is seen as long as two years post-transplant.

“The practical translation of our analysis suggests the use of pre-fecal microbial transplant treatments to reduce recipient microbial communities to facilitate a donor microbial strain-dominated gut microbial community following fecal microbial transplant,” said UAB researchers Hyunmin Koo, Ph.D., and Casey Morrow, Ph.D. “In addition, longitudinal sampling of individual fecal microbial transplant patients in combination with strain tracking analysis to monitor the status of the post-fecal microbial transplant microbial community would also be important to assess the stability and, ultimately, the success of the fecal microbial transplant.”

Koo and Morrow analyzed metagenomic sequencing published by Davar et al. in Science in 2021, using two established strain tracking methods, the WSS strain-tracking method developed at UAB and the strain-level population genomics tool StrainPhlAn. WSS can detect whether a donor strain or recipient strain of a particular species of gut microbes is dominant after fecal microbial transplants, and StrainPhlAn provides a phylogenetic tree of donor-related microbes or recipient-related microbes.

The Davar group gave fecal microbial transplants from patients who responded to anti-PD-1 immunotherapy for melanoma to recipient patients who were resistant to the immunotherapy, since it had been seen that the composition of the gut microbiota correlates with efficacy of anti-PD-1 therapy in animal models and cancer patients. Six out of 15 patients benefited.

Koo and Morrow analyzed five fecal microbial transplants by the Davar group where the recipient microflora was sampled multiple times for as long as 535 days post-fecal microbial transplant. This published metagenomic data allowed a time-series strain tracking analysis.

The UAB researchers found that three Alistipes bacterial species and one Parabacteroides species all had patterns, post-fecal microbial transplant, of either dominant donor or dominant recipient strains in the feces.

In contrast, Bacteroides uniformis and Bacteroides vulgatus showed inter-individual oscillation over time with the appearance of either donor or recipient fecal strain dominance. Adding further to the complexity, there were some instances of dominant strains of the two Bacteroides species that were unrelated to either the donor or the recipient strains. Also, one Bacteroides vulgatus strain showed a possible genetic recombination event between the donor and recipient strains.

“The complex oscillating patterns of the appearance of fecal dominant donor, recipient or unrelated strains following extended times post-fecal microbial transplant provide new insights into the dynamics of the microbial community interactions with the recipients following fecal microbial transplant,” Morrow said. “The result from our analysis has implications for the use of fecal microbial transplant to predictably change the biological functions of the gut community in metabolism and host immunity.”

Morrow is professor emeritus of the UAB Department of Cell, Developmental and Integrative Biology, and Koo is bioinformatician in the UAB Department of Genetics. Both departments are in the Marnix E. Heersink School of Medicine.

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Materials provided by University of Alabama at Birmingham. Original written by Jeff Hansen. Note: Content may be edited for style and length.

Research from Dr. Stuart Fogel, a cognitive neuroscientist, professor at the University of Ottawa’s School of Psychology, and researcher at the Royal’s Institute for Mental Health Research, is shedding light into how the impact of a person’s daily rhythm and activity levels during both wake and sleep relate to human intelligence. Contrary to the adage “the early bird gets the worm,” previous work suggests that evening types, or “owls,” have superior verbal intelligence.

Yet, “once you account for key factors including bedtime and age, we found the opposite to be true, that morning types tend to have superior verbal ability,” says Stuart Fogel, Director of the University of Ottawa Sleep Research Laboratory. “This outcome was surprising to us and signals this is much more complicated that anyone thought before.”

Fogel’s team identified individual’s chronotype — their evening or morning tendencies — by monitoring biological rhythms and daily preferences. A person’s chronotype is related to when in the day they prefer to do demanding things, from intellectual pursuits to exercise.

Young individuals are typically “evening types” while older individuals and those more regularly entrenched in their daily/nightly activities are likely “morning types.” The juxtaposition here is that morning is critical for young people, especially school aged children and adolescents, who have their schedules set by their morning-type parents and their routines. This might be doing youngsters a disservice.

“A lot of school start times are not determined by our chronotypes but by parents and work-schedules, so school-aged kids pay the price of that because they are evening types forced to work on a morning type schedule,” says Fogel.

“For example, math and science classes are normally scheduled early in the day because whatever morning tendencies they have will serve them well. But the AM is not when they are at their best due to their evening type tendencies. Ultimately, they are disadvantaged because the type of schedule imposed on them is basically fighting against their biological clock every day.”

The study enlisted volunteers from a wide age range, who were rigorously screened to rule out sleep disorders and other confounding factors. They outfitted volunteers with a monitoring device to measure activity levels.

Establishing the strength of a person’s rhythm, which drives intelligence, is key to understanding the results of this nuanced study, says Fogel, with a person’s age and actual bedtime proving important factors.

“Our brain really craves regularity and for us to be optimal in our own rhythms is to stick to that schedule and not be constantly trying to catch up,” adds Fogel.

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Materials provided by University of Ottawa. Original written by Paul Logothetis. Note: Content may be edited for style and length.

The study, published in JAMA Network Open on Wednesday, Nov. 2, examined the relationship between heat exposure and mortality risks in Texas prisons, focusing on how these risks vary between prisons with air conditioning and those without it.

The researchers analyzed data gathered between 2001 and 2019 showing that 271 people died due to extreme heat exposure during that timeframe.

Even a 1 degree increase above 85 degrees Fahrenheit can elevate the daily risk of dying by 0.7%, the researchers found.

The research team — which in addition to Brown also included scholars from Harvard University, Boston University and the organization Texas Prison Community Advocates — combined data from the U.S. Bureau of Justice Statistics on mortality in Texas prisons with temperature data from NASA and used a novel epidemiologic analysis to arrive at its findings. The team reported that approximately 13% of mortality during warm months may be attributable to extreme in Texas prison facilities without air conditioning.

It is important to note that while an average of 14 people died each year from heat-related causes in Texas prisons without air conditioning, not a single heat-related death occurred in climate-controlled prisons, said lead study author Julie Skarha, who received her Ph.D. in epidemiology from Brown in June 2022.

“The majority of Texas prisons do not have universal air conditioning,” Skarha said. “And in these settings, we found a 30-fold increase in heat-related mortality when compared to estimates of heat-related mortality in the general U.S. population.”

Study co-author Dr. David Dosa, an associate professor of medicine, and health services, policy and practice at Brown, pointed out that heat is often a silent killer.

“We have seen similar situations in nursing homes, where heat isn’t reported on the death certificate,” said Dosa, a practicing geriatrician with dual appointments at the Providence V.A. Medical Center and Rhode Island Hospital. “It’s only after we run these analyses that we can determine how much of a role heat played in someone’s death.”

The findings, the researchers said, suggest that an air conditioning policy for Texas prisons may be an important part of protecting the health of people living and working in these facilities.

Other study authors included Dr. Josiah Rich and David Savitz from Brown, Amite Dominick from Texas Prison Community Advocates, Keith Spangler from Boston University and Antonella Zanobetti from Harvard. The study was supported by grants from the National Institute on Minority Health and Health Disparities and from the National Institute of Environmental Health Sciences.

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Materials provided by Brown University. Original written by Carl Dimitri, Senior Writer, School of Public Health. Note: Content may be edited for style and length.