The research findings have been published in the academic journal Molecular Biology and Evolution.

Due to the general lack of photosynthesis-derived organic matter, the deep-sea was once considered a vast “desert” with very little biomass. Yet, clams often form large populations in the high-temperature hydrothermal vents and freezing cold seeps in the deep oceans around the globe where sunlight cannot penetrate but toxic molecules, such as hydrogen sulfide, are available below the seabed. The clams are known to have a reduced gut and digestive system, and they rely on endosymbiotic bacteria to generate energy in a process called chemosynthesis. However, when this symbiotic relationship developed, and how the clams and chemoautotrophic bacteria interact, remain largely unclear.

Horizontal gene transfer between bacteria and clams discovered for the first time

A research team led by Professor Qiu Jianwen, Associate Head and Professor of the Department of Biology at HKBU, collected the clam specimens at 1,360 metres below sea level from a cold seep in the South China Sea. The genomes of the clam and its symbiotic bacteria were then sequenced to shed light on the genomic signatures of their successful symbiotic relationship.

The team found that the ancestor of the clam split with its shallow-water relatives 128 million years ago when dinosaurs roamed the earth. The study revealed that 28 genes have been transferred from the ancestral chemoautotrophic bacteria to the clam, the first discovery of horizontal gene transfer — a process that transmits genetic material between distantly-related organisms — from bacteria to a bivalve mollusc.

The following genomic features of the clam were discovered, and combined, they have enabled it to adapt to the extreme deep-sea environment:

(1) Adaptions for chemosynthesis

The clam relies on its symbiotic chemoautotrophic bacteria to produce the biological materials essential for its survival. In their symbiotic relationship, the clam absorbs hydrogen sulfide from the sediment, and oxygen and carbon dioxide from seawater, and it transfers them to the bacteria living in its gill epithelium cells to produce the energy and nutrients in a process called chemosynthesis. The process is illustrated in Figure 1.

The research team also discovered that the clam’s genome exhibits gene family expansion in cellular processes such as respiration and diffusion that likely facilitate chemoautotrophy, including gas delivery to support energy and carbon production, the transfer of small molecules and proteins within the symbiont, and the regulation of the endosymbiont population. It helps the host to obtain sufficient nutrients from the symbiotic bacteria.

(2) Shift from phytoplankton-based food

Cellulase is an enzyme that facilitates the decomposition of the cellulose found in phytoplankton, a major primary food source in the marine food chain. It was discovered that the clam’s cellulase genes have undergone significant contraction, which is likely an adaptation to the shift from phytoplankton-derived to bacteria-based food.

(3) Adaptation to sulfur metabolic pathways

The genome of the symbiont also holds the secrets of this mutually beneficial relationship. The team discovered that the clam has a reduced genome, as it is only about 40% of the size of its free-living relatives. Nevertheless, the symbiont genome encodes complete and flexible sulfur metabolic pathways, and it retains the ability to synthesise 20 common amino acids and other essential nutrients, highlighting the importance of the symbiont in generating energy and providing nutrients to support the symbiotic relationship.

(4) Improvement in oxygen-binding capacity

Unlike in vertebrates, haemoglobin, a metalloprotein found in the blood and tissues of many organisms, is not commonly used as an oxygen carrier in molluscs. However, the team discovered several kinds of highly expressed haemoglobin genes in the clam, suggesting an improvement in its oxygen-binding capacity, which can enhance the ability of the clam to survive in deep-sea low-oxygen habitats.

Professor Qiu said: “Most of the previous studies on deep-sea symbiosis have focused only on the bacteria. This first coupled clam-symbiont genome assembly will facilitate comparative studies that aim to elucidate the diversity and evolutionary mechanisms of symbiosis, which allows many invertebrates to thrive in ‘extreme’ deep-sea ecosystems.”

The research was jointly conducted by scientists from HKBU and the HKBU Institute for Research and Continuing Education, the Hong Kong Branch of the Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), The Hong Kong University of Science and Technology, City University of Hong Kong, the Japan Agency for Marine-Earth Science and Technology, the Sanya Institute of Deep-Sea Science and Engineering, and the Guangzhou Marine Geological Survey.

The review study, published in Nature Reviews Earth & Environment, examined the effects climate change will have on hail in the future.

It shows a global summary of hail trends from past observations and projected future trends from simulations and models.

The review led to the general expectation that hailstorm frequency will decrease in East Asia and North America, while increasing in Australia and Europe, and that hailstorm severity will increase in most regions.

Researchers from University of Bern, Central Michigan University, Karlsruhe Institute of Technology, University of Illinois, Colorado State University and Peking University took part in the study.

“We came to the conclusion that on balance, the hail threat is likely to increase in Australia, especially in Australia’s south-east including the Sydney area,” lead author and postdoctoral researcher at UNSW Sydney’s Climate Change Research Centre, Tim Raupach said.

But the researchers say current and future climate change effects on hailstorms remain highly uncertain, in part due to a lack of long-term observations and limited modelling studies.

“There’s very high uncertainty when it comes to these predictions and Australia is particularly of high uncertainty because there are very few studies that have actually looked at Australia.

“We need to do further study to find out exactly what we expect to happen, not only in Australia but across the world.”

Changing atmospheric conditions

The study examined the general expectation that atmospheric ingredients that affect hail ¬- an unstable atmosphere, the amount of melting of falling hailstones, and wind shear or differences in wind by height — would change with a warming climate and lead to less frequent but more intense hailstorms.

“We know with climate change that we are going to have more moisture in the atmosphere and that leads to more instability in the atmosphere, so we expect there will be more tendency for thunderstorms to occur because of this unstable atmosphere,” Dr Raupach said.

Because the atmosphere will be warmer, the melting level ¬¬- which is the height in the atmosphere below which ice begins to melt ¬- will get higher, he said.

“So as a melting level gets higher, hail that forms high in the atmosphere and falls towards the ground has more time to melt and may indeed melt entirely before it gets to the ground, and you end up with no hail at the surface.”

Overall wind shear — a process that “organises” storms and makes them more severe — is expected to decrease, he said, but hail storms will be more affected by the other two factors.

“The changes you can expect of these three properties of the atmosphere lead us to expect that hail will be less frequent, because there’s more melting essentially in the future,” Dr Raupach said.

“But the hail will be more severe when it does occur, because there will be more instability in the atmosphere which can lead to the formation of much larger hailstones.

“So when the hail does survive this extra melting, it will be larger and more severe when it does actually hit the surface.”

The review showed, however, that this general expectation was not applicable everywhere, with reported hail changes differing in different parts of the world.

“Regional variability in the atmospheric changes leads to varying hail responses, which is why studies show increasing hail frequency in Europe but decreasing hail frequency in East Asia, for example,” said Dr Raupach.

Hail is difficult to measure

The study looked at trends in hailstorms from past observations, such as from meteorological stations, hail pads (sheets that record hail impacts), and crowdsourced or media reports.

Dr Raupach said there was high uncertainty in these trends because hailstorms are very difficult to measure due to their small scale and rarity.

“If you put out an instrument to capture [or] measure hail, even in a place where you might expect a lot of hail, you might only get one or two hits on that instrument in a year,” he said.

“If you are trying to look at climate change and long-term trends where you want decades of information, it’s very difficult to collect that kind of information about hail.”

The review also summarised results from simulations and model studies that project what the effects of climate change will be on hail in the future.

“You can see whether the model actually produces more hailstorms or less hailstorms in the future when you change the properties of the model, such as making the temperature higher or increasing the melting level height,” Dr Raupach said.

Because hailstorms are a small-scale phenomenon, they are difficult to model with regular weather models.

“You need to have a very high-resolution model to actually be able to resolve the size of the hailstorm,” Dr Raupach said.

“There have been a few of these studies but they are relatively rare and we need more of them to be able to understand how hail will change in the future with climate change.”

Recommendations ‘to reduce uncertainty’

To reduce the uncertainty about hailstorms and climate change, the researchers recommended recording long term observations with instruments such as hail pads in uncovered hail hotspots.

They also recommended improving so-called proxy relationships, which scientists use to try to statistically relate large-scale hailstorm “ingredients” in the atmosphere to the formation of hail that hits the surface.

“The problem we have with [these] proxy relationship[s] is that even when the atmosphere is thought to be prone to hail forming, it’s still relatively rare that hail actually forms,” Dr Raupach said.

Process-oriented studies which look at the details of how hail forms in clouds and then grows into large hail were also recommended to close current knowledge gaps.

“For example, a topic of current research is whether an increase of aerosols leads to an increase in hail formation or a decrease in hail formation,” Dr Raupach said.

The changing economic impacts of hail should also be studied, since changes to building materials, population growth, and crop cycles also change hail exposure.

“We expect the damages that can be caused by hail to also change in the future,” Dr Raupach said.

More high-resolution computer models, run at high-performance facilities such as the National Computational Infrastructure in Canberra, should be used in further research.

“As these systems come online, we are able to do high resolution studies that were previously too computationally expensive to actually run,” he said. “These models are going to be extremely useful for understanding how hail will change in a warming climate.”

In Barrett’s Esophagus (BE), chronic acid reflux from the stomach damages the cells lining the lower esophagus, causing them to become more like cells of the lower digestive system. Cells in the lower esophagus progress through several precancerous stages before sometimes developing into esophageal adenocarcinoma, a cancer with a five-year survival rate below 20 percent. BE is the only known precursor to esophageal adenocarcinoma.

Clinicians can detect these progressive states in BE by looking for chromosomal alterations known as aneuploidy — a common feature in most cancer cells — but until now the process has involved multiple biopsies.

A single esophageal brushing paired with the sequencing technique called RealSeqS is sensitive and specific enough to identify aneuploidy at several stages of BE progression, and can even match specific types of aneuploidy with specific stages of the disease, the researchers say.

“Aneuploidy has long been implicated in the development, initiation or progression of esophageal cancer but the assays or experimental methods to detect this have not been as easily achieved or as high throughput as we would have wanted to allow for clinical implementation,” says senior study author Chetan Bettegowda, M.D., Ph.D., Jennison and Novak Families Professor of Neurosurgery at the Kimmel Cancer Center.

The method could help clinicians identify people at higher risk of having BE progress to esophageal adenocarcinoma, “instituting more intensive follow-up for those patients or instituting treatments at earlier stages of the disease,” Bettegowda says.

Results were published online Jan. 21 in the journal Gastroenterology.

Esophageal brushing uses a soft brush attachment for an endoscope to collect cells from the esophageal lining. The method can sample cells from a larger surface area of the esophagus than a usual biopsy. Endoscopy, often with brushing, “is part of the standard of care for people who have Barrett’s,” Bettegowda says, so incorporating the aneuploidy detection method would not change substantially change clinical practice.

Only a few cells out of hundreds sampled through brushing may demonstrate aneuploidy, however, so combining brushing with massively parallel sequencing is key to finding these cells. The researchers used a technique called RealSeqS to look across more than 350,000 regions of the genome to identify specific chromosome arm alterations. RealSeqS can typically detect aneuploidy at the level of about 1 in 200 cells, which is necessary when large portions of the esophageal brushing are derived from normal cells, says study lead author Christopher Douville, the Kimmel Center researcher who designed RealSeqS.

“The method is quick and can process hundreds of samples cost effectively, making it an ideal choice for the BE research,” says Douville.

The researchers obtained esophageal brushings from patients without BE, with BE and no abnormal cells, with BE and either low or high-grade cell abnormalities, and patients with esophageal adenocarcinoma. They trained their identification system to distinguish brushings from BE patients without cell abnormalities from those with adenocarcinoma using samples from 79 patients. The research team then looked at samples from 268 patients to test whether the method could distinguish different stages of BE progression.

Bettegowda, Douville and their colleagues identified a threshold of aneuploidy that distinguished patients with high-grade cell abnormalities and adenocarcinoma from BE patients with no cell abnormalities. At this threshold, the method identified high-risk patients in 232 or 86.7% of cases.

The method also identified specific chromosomal arm changes at each stage of BE progression toward adenocarcinoma. Some of these specific changes have already been linked to disease stages by previous research, “but they were not comprehensive enough to be used in some diagnostic or prognostic way,” says Douville.

The researchers used these changes to develop an assessment tool they called BAD (Barrett’s Aneuploidy Decision), for distinguishing stages of BE progression. The tool could be especially useful for identifying high-risk individuals when cell biopsies look benign, because the BAD tool points out molecular changes that are linked to more aggressive disease, Bettegowda says.

“Aneuploidy is as universal a biomarker as we can find at the moment for cancer, so we are excited to see how we can employ this technology for a multitude of cancers,” he says. “We are optimistic that given the versatility of the RealSeqS assay that we could study other disease processes, other cancer types and potentially find other ways to intervene earlier.”

The work was supported by grants CA150964, CA163060, CA152756, and UH3 CA205105-03 from the National Institutes of Health; grants RA37 CA230400-01, U01CA230691, Oncology Core CA 06973, from Burroughs Wellcome Career Award for Medical Scientists; Earlier Detection of Cancers Using Non-Plasma Liquid Biopsies; The Virginia and D.K. Ludwig Fund for Cancer Research; The Sol Goldman Sequencing Facility at Johns Hopkins; and The Conrad R. Hilton Foundation.

Other contributors to the work were from Case Western Reserve University; University of North Carolina; and Mayo Clinic.

Co-authors Kenneth Kinzler, Nickolas Papadopoulos, and Bert Vogelstein are founders of and hold equity in Thrive and Personal Genome Diagnostics. Kinzler and Papadopoulos are consultants to and are on the Board of Directors of Thrive. Kinzler and Vogelstein are consultants to Personal Genome Diagnostics, Sysmex, Eisai, and CAGE Pharma. Vogelstein is also a consultant to Catalio and is compensated with equity. Kinzler, Papadopoulos, and Vogelstein are consultants to Neophore. Bettegowda is a consultant to Depuy-Synthes and Bionaut Labs. Douville is a consultant to Thrive and is compensated with income and equity. The companies named above as well as other companies have licensed previously described technologies related to the work described in this paper from Johns Hopkins University. Douville, Bettegowda, Kinzler, Papadopoulos and Vogelstein are inventors on some of these technologies. Licenses to these technologies are or will be associated with equity or royalty payments to the inventors as well as to Johns Hopkins University. The terms of all of these arrangements are being managed by Johns Hopkins University in accordance with its conflict of interest policies.