Researchers at the Big Data Institute and colleagues have developed a new method for understanding the relationships between different DNA sequences and where they come from.

This information has widespread applications, from understanding the development of viruses, such as SARS-CoV-2, the strain of coronavirus that causes COVID-19, to precision medicine, an approach to disease treatment and prevention that takes into account individual genetic information. The study is published in GENETICS and is the featured paper in the September 2024 edition.  

Genetics is rapidly becoming part of our everyday lives. Nearly every week sees another newspaper headline about genetics and human ancestry, with huge datasets of DNA sequences routinely generated and used for medical study.

We can make sense of this genomic big data by working out the historical process that created it ‒ in other words, where the DNA sequences came from. If we take a small section of someone’s DNA we know it must have come from one of their two parents in the last generation, and previously from one of their four grandparents in the generation before that, and so on. This means we can represent the history of different sections of DNA by tracing them backwards through time.

If we do this for a large set of DNA sequences from different people, we can build up a set of genetic “family trees,” a genealogy of DNA sequences. This grand network of inheritance is sometimes called an ancestral recombination graph (ARG). Previous work by the same research group has shown that such networks can be used not only to illuminate the history of our genome, but also to compress DNA data and speed up genetic analyses.

Lead author and evolutionary geneticist at the Big Data Institute, Dr Yan Wong said, “There has been surprisingly little consensus on exactly how to represent such an ancestral recombination graph on a computer. In this study, we outline a simple and efficient encoding of genetic genealogies in which each ancestor can be thought of as a fragmentary length of DNA, or ‘ancestral genome’ at some point in the past. The history of today’s genetic sequences is traced back through those ancestral genomes, keeping track of which chunks of DNA were inherited from which ancestors.”

By using this simple scheme, recording genome-to-genome transmission of information, the study shows that the same genetic ancestry can be stored to different degrees of precision. This means relationships between different DNA sequences can be represented without having to know or guess the precise timing of joins and splits that underlie the true history of inheritance. The researchers also show that their description of genetic inheritance is flexible enough to deal with the wide variety of different methods that researchers currently use to reconstruct genetic history.

The approach allows scientists to store and analyze large amounts of genetic data on a standard laptop, and it generalizes to any species of life on earth. For example, it forms the basis of a “unified genealogy” of over 7,000 publicly available whole human genome sequences that the researchers released previously. They are currently creating a genetic genealogy of millions of SARS-CoV-2 genomes, collected over the span of the coronavirus pandemic, which will allow analysis of the recent history of the virus, pinpointing the emergence of novel mixed (or “recombinant”) strains. Dr Wong added, “We hope that this formal standard for how to represent genetic genealogies can help to unify the field of genetic history and make it easier for scientists to analyze, share and compare results. This will be crucial as we move into an era of genomic medicine, where genetic data will be used to diagnose and treat diseases, and where understanding the history of our genomes will be key to understanding our health and ancestry.”

Look at any list of the top 10 most aggressive animals, and you will undoubtedly find a mugshot of the North American wolverine. Although much smaller than most of the other animals accompanying it on such lists—such as the hippopotamus and the wild boar—this feisty member of the weasel family has been a protagonist in popular myths, even serving as inspiration for superhero characters and as mascots of sports teams. A wide range of cultural, social, economic, and psychological factors influence human-wolverine relations. In many Indigenous societies, the wolverine is a respected cultural keystone species and is often viewed as a trickster. Unfortunately, these solitary carnivores rely on cold temperatures and snowy environments for their reproduction and survival, so their future remains uncertain in a warming world.

A new study published in the August issue of G3: Genes|Genomes|Genetics provides geneticists and conservation biologists with a high-quality, chromosome-level genome assembly of the wolverine, including extensive annotation of genes involved in behavior and immune responses to pathogens. The authors’ goal goes far beyond the wolverine: they seek to provide similar high-quality assemblies for other species predicted to be impacted by increasing global temperatures. This means setting the benchmark for a workflow that offers the best compromise possible when balancing cost, time, simplicity, accuracy, and completeness for long-read assembly and genome annotation. 

“Our goal is to replace the existing short-read assemblies and increase the quality standards for new reference genomes in light of current sequencing technologies,” says lead author Si Lok.

Improving the standards of genome assembly in the current era

The DNA sequenced in the report comes from a 30-year-old tissue sample of a male wolverine specimen from the Kugluktak (Coppermine) region of Nunavut. Lok and colleagues use PacBio contiguous long-reads (CLR) mode, which typically provides maximal read length at a reasonable cost; however, it is prone to 15-20% pseudo-random errors. To mitigate such inaccuracies while maintaining the numerous benefits of this approach, the authors used a two-step workflow for genome assembly: 1) the uncorrected CLRs are assembled using Flye assembler, followed by a polishing regimen with high-quality Illumina short reads, and 2) the subsequent scaffolding of the assembly against assemblies of related family members.

“It took us nearly two years to optimize a workflow that produces a final genome assembly comprising well less than 1000 contigs—about 10–100 times better than those found in most genome reports—at a cost of under $10,000,” says Lok. The cost is going down all the time.

This new workflow leads to striking completeness and accuracy: 99.98% of the current BUSCO set of 9,226 genes used to assess assembly quality are complete at exon-level in the wolverine assembly, placing it in the top tier of assemblies produced from long-reads. Lok hopes that their report shows how cost-effective, accurate, and complete sequencing and assembly can be nowadays. “No future genome reports should be less than chromosome-level, given the current technologies.”

Conservation genomics meets wolverine behavior

The new article also provides the first full-length mitochondrial genome assembly for the North American wolverine, as well as a tabulation of potential microsatellite markers for the wolverine. Since monitoring population size and distribution, reproductive success, and gene flow in wild populations often relies on analyses of mitochondrial DNA and microsatellites, the authors hope to provide a resource for developing these and other species-specific genomic markers.

In addition, Lok and colleagues annotated genes whose orthologs have been associated with aggressive traits in other organisms—an adaptation to drive competition for food and mates— and the key components of innate immune responses. “Environmental disruptions from climate change will increase vulnerabilities to new pathogens,” says Lok.

“We are in the process of reporting genomes for other species predicted to be heavily affected by climate change in efforts to support their conservation and ecological relationships, such as that of the Canada lynx and the snowshoe hare,” says Lok. He wishes this report to set a minimum standard of quality for future genome reports and resources for conservation biologists.

Scientists generated a karyotype, chromosome-scale genome assembly, and manual genome annotation for a common ctenophore.

Ctenophores—beautiful marine invertebrates also known as “comb jellies”—have long fascinated and perplexed biologists. Phylogeneticists believe that either ctenophores or sponges were the first organisms to branch off from the tree of life, making them the “sister clade” to all other animals. However, debate is ongoing about which group can claim this title.

A study published in G3: Genes|Genomes|Genetics provides researchers with new tools to address these questions. The paper describes the first-ever published ctenophore karyotype and the first full annotated genome assembly for Hormiphora californensis, a small, globular ctenophore that is found off the shores of California and elsewhere in the Pacific Ocean.

The chromosome-scale H. californensis genome will allow whole-genome comparisons that weren’t possible with previous assemblies, says lead author Darrin Schultz. “The applications go beyond studying ctenophores—we can compare this genome to that of any other species to look for differences and understand more about the history of evolution.”

Going Over the Genome with a Fine-Toothed Comb

Schultz and his fellow researchers started with karyotyping, using a simple DNA staining protocol on ctenophore embryos to determine that H. californensis has 13 chromosomes. Then, after successfully isolating DNA samples suitable for long-read sequencing—a feat in and of itself—the team used PacBio Iso-Seq and Illumina RNA-seq technologies to sequence and annotate the full 110-Mb genome, manually determining at high resolution how genes were arranged on each chromosome.

“We spent hundreds of hours going through the entire genome by hand and making sure that every single gene annotation was correct,” says Schultz. “We did this because we saw evidence that previous ctenophore genome assemblies contained incorrect fusions or splits in genes. We wanted it to be right this time.”

As the researchers sifted through the genome, they found that H. californensis has an unusually high degree of heterozygosity—up to eight or nine percent in some areas of the genome. This presented bioinformatic challenges.

“The copies of the genome from the maternal side and the paternal side are so different from each other that it was like I had to assemble two separate genomes and try to come up with one assembly to represent both of those unions at the same time,” says Schultz.

As they got further into the annotation process, the team realized that two to three percent of the protein-coding genes occur completely within the bounds of another gene—not just one inside another, but multiple genes nested like Russian dolls. This architectural quirk has been observed in other species, especially eukaryotes with smaller genomes, but scientists are not yet sure whether the transposition processes that likely cause this “nesting” have any implications for the overall biology of an organism.

Comparative and Evolutionary Studies in Store

The new annotated ctenophore genome assembly will likely be used for comparative studies to address the phylogenetic “sister clade” debate between ctenophores and sponges in the coming years. Other applications of this study include addressing even broader questions about life on Earth. Some researchers are studying the genetic underpinnings of symbiosis using marine models like corals, ctenophores, and other cnidarians that have symbiotic algae. Others are interested in using comparative genomic studies to examine the evolution of specific traits that separate animals from all other organisms.

“This genome is just another step toward understanding how neurons and muscle cells—these things that made all of us uniquely animals—evolved over 600 million years ago,” says Schultz.

Schultz also notes that H. californensis may eventually be able to become a model species. It has a short life cycle, clear embryos ideal for developmental observation, and is more easily maintained in culture than many other related organisms. And now, it has a complete annotated genome available for study.

CITATION:

A chromosome-scale genome assembly and karyotype of the ctenophore Hormiphora californensis
Darrin T Schultz, Warren R Francis, Jakob D McBroome, Lynne M Christianson, Steven H D Haddock, Richard E Green
G3 Genes|Genomes|Genetics 2021: jkab302
https://doi.org/10.1093/g3journal/jkab302

Improved duplex sequencing identifies spontaneous mutations in bacteria without long-term culturing.

Spontaneous mutations are the driving force of evolution, yet, our ability to detect and study them can be limited to mutations that accumulate clonally. Sequencing technology often cannot identify very rare variants or discriminate between bona fide mutations and errors introduced during sample preparation. In GENETICS, Zhang et al. created an improved sequencing method to study low-abundance spontaneous mutations in the bacterium Escherichia coli.

To develop their method, the authors began with duplex sequencing, in which fragmented DNA molecules are tagged with an adaptor sequence for sequencing. This method is powerful, but at high read depths, it can erroneously call true mutations as PCR duplicates, making it ill-suited for finding rare mutations.

The authors first determined the error rate of the PCR step of duplex sequencing, where most experimental artifacts would be expected to occur. Because duplex sequencing can identify reads that came from the same parental DNA molecules (based on the adaptor sequences), the authors assumed that any such reads that had mismatches must have come from base changes during the PCR. By identifying these discrepancies, they determined the rates of different kinds of errors in the sequencing process.

The authors then sequenced E. coli genomes using a new method, which they termed improved duplex sequencing (IDS). IDS is similar to duplex sequencing, but it uses adaptor sequences of multiple different lengths. The use of more and different adaptor sequences minimizes the chance that two different DNA molecules that happen to break at the same place will be erroneously called as PCR replicates. By employing this method and accounting for the error rate of the PCRs, which they had already determined, the authors were able to confidently identify rare, random mutations in E. coli.

Having identified such mutations, the authors looked for patterns. They found that clusters of mutations occurred in regions of the genome that are known to be replication fork stopping regions. This is suggestive of transcriptional errors, as would be expected for spontaneous mutations. Interestingly, mutations in these hotspots were almost entirely in relatively unimportant regions of the genome—for instance, in the non-functional parts of tRNA genes. These vulnerable areas of the genome hint at mechanisms in E. coli that may protect more critical regions from damage.

CITATION:

Spatial Vulnerabilities of the Escherichia coli Genome to Spontaneous Mutations Revealed with Improved Duplex Sequencing

Xiaolong Zhang, Xuehong Zhang, Xia Zhang, Yuwei Liao, Luyao Song, Qingzheng Zhang, Peiying Li, Jichao Tian, Yanyan Shao, Aisha Mohammed AI-Dherasi, Yulong Li, Ruimei Liu, Tao Chen, Xiaodi Deng, Yu Zhang, Dekang Lv, Jie Zhao, Jun Chen, Zhiguang Li

Genetics October 2018 210: 547-558; https://doi.org/10.1534/genetics.118.301345

https://www.genetics.org/content/210/2/547

An opportunistic human pathogen makes itself at home on old oaks.

At one point or another, most people have played host to the common yeast Candida albicans. Around 40-60% of healthy adults carry around it in their mouth or guts; in immunocompromised people, however, this normally harmless cohabitant becomes a deadly pathogen. Generally thought to only grow in warm-blooded animals, C. albicans has occasionally been isolated from plants—from blades of grass in a New Zealand pasture to gorse and myrtle plants on a sheep-grazed hill in Portugal to an African tulip tree in the Cook Islands. Are these just cases of misplaced yeast, or can C. albicans really thrive outside a warm body? In a report in GENETICS, Bensasson et al. describe the genomes of three C. albicans strains isolated from the barks of oak trees in an ancient wood pasture, providing genetic evidence that this yeast can live on plants for extended periods of time.  

A survey of budding yeast on oaks in Europe turned up three new strains of C. albicans; they were found only on some of the oldest trees. After ensuring that the new strains were indeed new tree-based isolates (and not merely laboratory contaminants), the authors conducted a phenotypic investigation. All three strains showed most of the standard traits of C. albicans, including the ability to grow at the elevated temperatures expected in a mammal; however, they were not identical. One of the strains was not as salt tolerant as the others, would not grow on soluble starch, and switched to a different growth form under particular nutritional conditions.

The authors next sequenced the genomes of the new strains; this was the first time C. albicans from a non-animal source have been sequenced. Genomic analysis showed that the three strains were relatively distantly diverged from each other, and the new sequences were compared with over 200 yeast sequences previously isolated from humans and other animals to create a phylogenetic tree. Interestingly, all three of the tree strains showed more similarity with clinical strains than with each other.

The authors also analyzed the levels of heterozygosity—a measure of genetic variation—within the tree strains and found that these strains are more heterozygous than typical clinically isolated strains, which suggests that life on trees subjects the yeast to different selection or mutation pressures than life in humans. Higher heterozygosity could be a result of yeast evolving in conditions where they have to reproduce asexually, which would make mutations more likely to accumulate, thus increasing allelic variation. This difference also supports the idea that these yeast grow in the wild, rather than being recent emigrants from a warm-blooded host.

These findings may have implications beyond the shady groves of the New Forest; understanding the wild life of C. albicans could shed light on the evolution and lifestyle of the yeast found in humans and help us better understand how virulent strains emerge and damage human health.

CITATION:

Diverse Lineages of Candida albicans Live on Old Oaks

Douda Bensasson, Jo Dicks, John M. Ludwig, Christopher J. Bond, Adam Elliston, Ian N. Roberts, Stephen A. James

Genetics January 2019 211: 277-288; https://doi.org/10.1534/genetics.118.301482

http://www.genetics.org/content/211/1/277

A new collection of inbred flies provides a tool for studying genetic control of sleep.

Sleep is vital for a healthy life, but some of us seem to get by with less snoozing than others. This individual variation isn’t unique to humans; fruit flies also show a variety of sleep patterns. These differences could potentially reveal more than just which flies are consistent cat-nappers—understanding the genetic basis of sleep variation could help pinpoint some of the molecular mechanisms that govern this essential and evolutionarily conserved process. In G3: Genes|Genomes|Genetics, Serrano Negron et al. describe a collection of inbred fly lines with extreme sleep behaviors that will serve as a useful tool for exploring such questions.

In a previous study, the authors had worked with flies from the Drosophila Genetic Reference Panel (DGRP), which is a large panel of inbred lines derived from a natural population. They chose the five longest-sleeping and five shortest-sleeping DGRP lines and allowed them to cross at random for 21 generations to produce an outbred population. They then used artificial selection to produce two long-sleeping and two short-sleeping populations.

In the new report, the authors created inbred lines from these long-sleeping and short-sleeping populations. Creating inbred lines is useful for gene editing studies because it reduces experimental noise caused by background genetic variation. To create lines of flies that sleep for either a very long or very short time, they mated one male and one female from one of the selected populations and then selected one male and one female from the progeny to propagate the line. They repeated this for 20 generations, eventually creating 39 inbred lines (19 long-sleeping lines and 20 short-sleeping lines), which were termed the Sleep Inbred Panel.

The duration of night sleep in the inbred lines ranged from just over an hour to nearly 11.5 hours, confirming that the extremes of the phenotypes had been maintained in the lines. The phenotypes were comparable to the selected parental populations, showing that the inbreeding process reduced genetic variability without drastically altering the sleep patterns. Interestingly, most of the variation between the new panel and the parental populations was due to short-sleeping inbred flies sleeping a little more than parental flies, which is likely because short sleep times made the flies less fit. Individual short-sleeping flies also showed more variation in how much they slept, likely for similar reasons.

By sequencing the genomes of flies in the panel, the authors identified a number of SNPs and other genomic variations associated with the sleep phenotypes, and they traced many of these variations back to the original DGRP lines. This resource can now be used to study the genetic underpinnings of sleep and may one day help shed light not only on ordinary differences between night owls and early birds but also on the causes of devastating sleep disorders.

Citation:

The Sleep Inbred Panel, a Collection of Inbred Drosophila melanogaster with Extreme Long and Short Sleep Duration

Yazmin L. Serrano Negron, Nancy F. Hansen, Susan T. Harbison

G3: Genes, Genomes, Genetics September 2018 8: 2865-2873;

https://doi.org/10.1534/g3.118.200503

http://www.g3journal.org/content/8/9/2865

Low-cost sequencing closes gaps in fly genomes.

Genetic sequencing technologies have revolutionized biological science, and regular advances in these tools continue to deliver better genomic data—more accurate and more useful—at a lower cost. In G3: Genes|Genomes|Genetics, Miller et al. report the genomes of 15 Drosophila species sequenced using Oxford Nanopore technology. Their work improves on prior assemblies and describes how this technology can be feasibly applied in other labs.

Nanopore sequencing is an example of “third-generation” or “long-read” sequencing technology. In contrast to “next-generation” sequencing, which typically generates reads of a few hundred base pairs in length, the Nanopore approach can produce reads of several kilobases. This allows for better coverage and deeper sequencing, but it can also make the sequencing process more error-prone.

The authors used the Oxford Nanopore MinION to sequence 15 Drosophila species, all but one of which had been previously sequenced. They also resequenced the genome of Drosophila melanogaster and published their results in a separate report. When compared against reference sequences, their sequences captured a respectable amount of the published genomes (about 83% of the total sequences, on average). To correct for sequencing errors, they employed the polishing algorithms Racon and Pilon, which correct the genome sequences using reference Nanopore reads or Illumina reads, respectively. The polishing algorithms significantly increased assembly quality without altering other assembly statistics.

Because Nanopore sequencing produces longer reads, the authors wondered whether their data might be able to close gaps in existing reference sequences that were generated by short-read technology. By aligning short contigs from the reference genomes to their assemblies, they were able to fill ~61% of gaps in the reference genomes, demonstrating how the combination of newer and older technologies can increase the accuracy of genome builds.

The authors also describe how Nanopore technology can be readily applied in a variety of labs. They offer advice for sequencing and bioinformatics protocols. They found that using 1-10 µg of input DNA yielded better results than the factory-recommended 400 ng and that the de novo assembler miniasm used fewer computational resources than alternatives but produced comparable products. Excitingly, the material cost of sequencing of the reported Drosophila genomes was about $1000 USD, meaning that genome sequencing via Oxford Nanopore is likely feasible for labs of all sizes.

CITATION:

Highly Contiguous Genome Assemblies of 15 Drosophila Species Generated Using Nanopore Sequencing

Danny E. Miller, Cynthia Staber, Julia Zeitlinger, R. Scott Hawley

G3: Genes, Genomes, Genetics October 2018 8: 3131-3141; https://doi.org/10.1534/g3.118.200160

http://www.g3journal.org/content/8/10/3131

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A strain of Staphylococcus epidermidis isolated from a hotel room may provide insight into how resistance develops outside of medical settings.

Although intense research and media interest has focused on drug-resistant bacteria in hospital settings, resistance can and does evolve outside the clinic. Methicillin-resistant Staphylococcus epidermidis is often isolated from infections of medical devices, but in a report in G3: Genes|Genomes|Genetics, Xu et al. studied drug resistance in a strain that was isolated from a public setting: a hotel room in London.

Although S. epidermidis isn’t as virulent as its infamous relative S. aureus, it can still cause infection and serve as an important reservoir for resistance genes, which can be transferred to more deadly bacteria. The authors sequenced the genome of their strain and tested its susceptibility to a panel of antibiotics.

After sequencing the new strain’s genome, the authors found that its chromosome and six plasmids contained a number of resistance genes, including the fosfomycin resistance gene fosB, the multidrug resistance gene msrA, and several others. A comparison between the hotel strain and other sequenced S. epidermidis genomes revealed that some of these genes were unique to the new isolate, such as the tetracycline resistance gene tet(K). They also tested the strain’s susceptibility to a panel of thirteen antibiotics and found that it was resistant to eleven of them.

This is the first genomic analysis of an S. epidermidis strain isolated from a general public setting,  and it demonstrates how antibiotic resistance can occur even outside of the specific evolutionary pressures of a sterile healthcare setting. More studies like this may help us to further understand—and combat—the spread of antibiotic-resistance among our ever-present bacterial guests.

CITATION:

Whole Genome Sequence and Comparative Genomics Analysis of Multi-drug Resistant Environmental Staphylococcus epidermidis ST59

Zhen Xu, Raju Misra, Dorota Jamrozy, Gavin K. Paterson, Ronald R. Cutler, Mark A. Holmes, Saheer Gharbia, Hermine V. Mkrtchyan

G3: Genes, Genomes, Genetics July 2018 8: 2225-2230; https://doi.org/10.1534/g3.118.200314

http://www.g3journal.org/content/8/7/2225

Sequencing a genome is not as simple as reading a book. All those neatly lined up letters are the final product of a complex process made up of many intricate steps that can—and do—go wrong. In a report published in G3: Genes|Genomes|Genetics, Peccoud et al. put their painful sequencing experiences to good use providing new insights into a common sequencing problem: artificial chimeras.

Sequencing typically requires cutting up genetic material into fragments. These fragments are then amplified by PCR, and these amplified fragments are then sequenced. The end result is millions of short sequences, called reads. These reads can then be aligned to a reference sequence to identify changes like recombination and mutations.

The authors of the G3 study originally set out to identify recombination events between dengue virus and its host mosquito. They sequenced RNA from virus-infected mosquito cells, and they added pillbug RNA to a separate batch to serve as a control. Unexpectedly, the authors found virus-mosquito and virus-pillbug recombinant reads at similar frequencies. Since the virus RNA had never been in contact with the pillbug RNA before the sequencing procedure, they concluded that most, if not all, of these recombination events must have happened during the amplification or sequencing steps.

False-positives are always disappointing, but instead of giving up, the authors used their data and data from previous studies to better understand how the artificial reads occurred, as well as to learn how to better filter them.

This investigation revealed certain characteristics that are shared by both real and fake recombinant reads, including microhomology around the recombination junction. Crucially, they found that biologically-generated recombination almost always joins sequences in the same orientation, whereas artificial recombinant reads are often joined in opposite directions. The authors explain that this is likely due to template switching during the PCR step of sequencing.

Knowing the traits of false-positive reads may allow researchers to more carefully filter their data in future studies, ensuring they get the most accurate information possible—and knowing that what appears to be a dead end can still yield useful insights may help graduate students sleep better at night.

CITATION

A Survey of Virus Recombination Uncovers Canonical Features of Artificial Chimeras Generated During Deep Sequencing Library Preparation

Rhinocladiella mackenziei is a fungus that infects the human brain. It is the most common cause of neurological fungal infections in arid regions of the Middle East, and it is fatal in 70% of cases. However, little is understood about this lethal pathogen—not even its natural habitat.

To learn more about the biology of R. mackenziei, Moreno et al. turned to its genome. They resequenced the genome of two strains isolated from patients and compared them to known sequences from R. mackenziei, as well as other related fungi.

These comparisons gave clues about the natural lifestyle of the fungus. For example, R. mackenziei carries genes similar to fungi from habitats polluted by aromatic hydrocarbons, such as those found in gasoline. This suggests that R. mackenziei might flourish in oil-contaminated desert soil, where these genes would give it a competitive advantage over organisms that are unable to thrive in such a harsh environment.

The authors also identified a number of secreted virulence factors which could permit R. mackenziei to more easily establish itself in the brains of infected humans. The genomes harbor a wide array of genes involved in metabolism of diverse substrates, as well as nitrogen and iron uptake. This metabolic adaptability means that R. mackenziei probably isn’t a true pathogen; a pathogen would have lost some of these pathways because it could rely on its host for nutrients. Rather, this desert fungus is equipped to survive a number of harsh conditions, so its ability to infect human brains is most likely opportunistic.

CITATION

Genomic Understanding of an Infectious Brain Disease from the Desert