Tag Archives: genetics

Your microbiota will be having non-stop sex this Valentine’s Day

Even if you’re alone this Valentine’s Day, there’s no need to worry: some parts of your body will be getting plenty of action. In fact, your body will host a veritable carnival of the sensual in your tummy, as your microbiota will engage in an orgy of sex and swinger’s parties — where they’ll be swapping genes instead of keys.

A medical illustration of drug-resistant, Neisseria gonorrhoeae bacteria. Original image sourced from US Government department: Public Health Image Library, Centers for Disease Control and Prevention. Image in the public domain.

The salacious gene

Imagine you have a severe disease with a very unusual cure: you can treat by making love with someone who then passes on the necessary genes to cure your ailment. It is, as they say, sexual healing. Using sex to protect or heal themselves is precisely what bacteria can do, and it’s a crucial defense mechanism.

In the past, the research community thought bacterial sex (or conjugation, as scientists call it) was a terrible threat for humans, as this ancient process can spread DNA capable of conveying antibiotic resistance to their neighbors. Antibiotic resistance is one of the most pressing health challenges the world is facing, being projected to cause 10 million deaths a year by 2050.

But there’s more to this bacterial sex than meets the eye. Recently, scientists from the University of Illinois at Urbana-Champaign and the University of California Riverside witnessed gut microbes sharing the ability to acquire a life-saving nutrient with one another through bacterial sex. UCR microbiologist and study lead Patrick Degnan says:

“We’re excited about this study because it shows that this process isn’t only for antibiotic resistance. The horizontal gene exchange among microbes is likely used for anything that increases their ability to survive, including sharing vitamin B12.”

For well over 200-years, researchers have known that bacteria reproduce using fission, where one cell halves to produce two genetically identical daughter cells. However, in 1946, Joshua Lederberg and Edward Tatum discovered bacteria could exchange genes through conjugation, an entirely separate act from reproduction.

Conjugation occurs when a donor and a recipient bacteria sidle up to each other, upon which the donor creates a tube, called a pilus that attaches to the recipient and pulls the two cells together. A small parcel of DNA is then passed from the donor to the recipient, providing new genetic information through horizontal transfer.

Ironically, it wasn’t until Lederberg met and fell in love with his wife, Esther Lederberg, that they made progress regarding bacterial sex.

Widely acknowledged as a pioneer of bacterial genetics, Esther still struggled for recognition despite identifying the horizontal transfer of antibiotic resistance and viruses, which kill bacteria known as bacteriophages. She discovered these phages after noticing small objects nibbling at the edges of her bacterial colonies. Going downstream to find out how they got there, she found these viral interlopers hiding dormant amongst bacterial chromosomes after being transferred by microbes during sex.

Later work found that environmental stresses such as illness activated these viruses to replicate within their hosts and kill them. Still, scientists assumed that bacterial sex was purely a defense mechanism.

Esther Ledeberg in her Stanford lab. Image credits: Esther Lederberg.

Promiscuity means longevity

The newly-published study builds on Esther’s work. The study authors felt this bacterial process extended beyond antibiotic resistance. So they started by investigating how vitamin B12 was getting into gut microbial cells, where the cells had previously been unable to extract this vitamin from their environment — which was puzzling as, without vitamin B12, most types of living cells cannot function. Therefore, many questions remained about how these organisms survived without the machinery to extract this resource from the intestine.

The new study in Cell Reports uses the Bacteroidetes species, which comprise up to 80% of the human microbiome in the intestines, where they break down complex carbohydrates for energy.

“The big, long molecules from sweet potatoes, beans, whole grains, and vegetables would pass through our bodies entirely without these bacteria. They break those down so we can get energy from them,” the team explained.

This bacteria was placed in lab dishes mixing those that could extract B12 from the stomach with some that couldn’t. The team then watched in awe while the bacteria formed their sex pilus to transfer genes enabling the extraction of B12. After the experiment, researchers examined the total genetic material of the recipient microbe and found it had incorporated an extra band of DNA from the donor.

Among living mice, something similar happens. When the group-administered two different subgroups of Bacteroidetes to a mouse – one that possessed the genes for transferring B12 and another that didn’t — they found the genes had ‘jumped’ to the receiving donee after five to nine days.

“In a given organism, we can see bands of DNA that are like fingerprints. The recipients of the B12 transporters had an extra band showing the new DNA they got from a donor,” Degnan said.

Remarkably, the team also noted that different species of phages were also transferred during conjugation, exhibiting bacterial subgroup specificity in some cases. These viruses also showed the capacity to alter the genomic sequence of its bacterial host, with the power to promote or demote the life of its microbic vessel when activated.

Sexual activity in our intestines keeps us healthy

Interestingly, the authors note they could not observe conjugation in all subgroups of the Bacteroidetes species, suggesting this could be due to growth factors in the intestine or a possible subgroup barrier within this large species group slowing the process down.

Despite this, Degnan states, “We’re excited about this study because it shows that this process isn’t only for antibiotic resistance.” And that “The horizontal gene exchange among microbes is likely used for anything that increases their ability to survive, including sharing [genes for the transport of] vitamin B12.”

Meaning that bacterial sex doesn’t just occur when microbes are under attack; it happens all the time. And it’s probably part of what keeps the microbiome and, by extension, ourselves fit and healthy.

Pap tests could one day tell women if they have breast or ovarian cancer

Experts have identified changes in a woman’s cervix that can help detect tumors elsewhere in the body. These tests involve scraping cells from the cervix to detect any abnormalities that could cause cervical cancer. But researchers from Innsbruck University and gynecological cancer research charity The Eve Appeal found the cells from this test can also give clues and alerts for other types of cancers. With development, they state that the method used could one day predict the risk of developing ovarian, breast, womb, and cervical cancers from a straightforward smear pap test.

They developed their system using a process known as DNA methylation — epigenetic modifications to DNA that don’t alter the genetic sequence but do determine whether a gene expresses or stifles its function: in this case, forming or preventing cancer in the body. These modifications leave ‘methylation markers or signatures’ on genomic regions that scientists can read to determine what has occurred within a person’s body throughout their lifetime. Akin to the rings of a tree, this method can provide chronological clues as to what has happened in our biological life.

Researchers created the test, dubbed WID (Women’s Risk Identification), to analyze markers left by cancerous activity in the DNA of cervical cells. By calculating a woman’s WID, they hope to identify those with a high risk of developing ovarian, breast, womb, or cervical cancers: providing an early-warning system for medical teams to increase treatment outcomes.

The team was able to spot these modifications because they matched DNA markers found in diseased cervical, breast, ovarian, and womb biopsy tissue (a highly invasive procedure) to those found in the easier to access cells of the cervix — whose similar biological structures undergo the same hormonal changes as the tissues these cancers flourish in.

Finding cancer through the cervix

The first study examined cervical cell samples collected from 242 women with ovarian cancer and 869 healthy controls. To develop the WID risk scale, the scientists measured 14,000 epigenetic changes to identify ovarian cancer’s unique DNA signature to spot the presence of the disease in epithelial tissue scraped from the cervix.

They then validated the signature in an additional cohort of 47 women who had ovarian cancer and 227 healthy subjects. Results identified 71% of women under 50 and roughly 55% of the volunteers older than 50 who had previously tested positive for the disease — giving the tests an overall specificity of 75%. A test’s specificity is its ability to correctly identify people without the disease.

Professor Martin Widschwendter of the University of Innsbruck and UCL, heading up the research, said the findings suggest their WID index is picking up cancer predisposition, adding that the results were similar to a study on women with cancer of the womb. He is adamant their test cannot predict ovarian, with more studies needed.

A possible screening method for an undetectable cancer 

In the second study, the same team analyzed epigenetic changes in cervical cell samples provided by 329 women with breast cancer against those from the same 869 healthy volunteers in the first study. Using the WID index, they were able to identify women with breast cancer based on a unique epigenetic signature. The group once again confirmed these markers in a smaller consort of 113 breast cancer patients and 225 women without this condition.

The researchers also used the patterns to predict whether patients had breast cancer-but they didn’t say exactly how accurate the tests were. Instead, they stressed that further trials are needed-with the hope that clinicians could use their WID as a regular test for women in the future-specifically for those under fifty years of age who do not have access to screening for this disease.

“This research is incredibly exciting,” said Liz O’Riordan, a breast cancer surgeon who was also diagnosed with this disease. “At the moment, there is no screening test for breast cancer in women under the age of 50. If this test can help pick up women with a high risk of developing breast, ovarian, cervical, and uterine cancer at a younger age, it could be a game-changer.”

The team adds that these findings are also crucial for ovarian cancer, whose symptoms can be as benign as a bloated abdomen. The biggest killer of women out of gynecological-based tumors, this disease is diagnosed late by clinicians in an alarming 3 out of four cases.

But for now, Widschwendter says, the findings suggest that the molecular signatures in cervical cells may detect the predisposition to other women-specific cancers rather than providing a solid prediction of the disease.

Because of the pandemic, women have stopped taking pap tests

A pap smear test detects abnormal cells on the cervix, which is the entrance to the uterus from the vagina. Removing these cells can prevent cervical cancer, which most commonly affects sexually-active women aged between 30 and 45. In most cases, the human papillomavirus causes this cancer after being acquired through unprotected sex or skin-to-skin contact. To summarise, the whole point of these tests is to detect women at risk of developing cancer and encourage them to carry further health check-ups, not to find those displaying cancer symptoms.

Around the world, the number of women taking smear tests has dropped substantially during the pandemic. In England, for instance, one of the countries with the highest testing rates, just 7 out of 10 eligible women got a cervical check-up — and conditions are expected to worsen due to a new policy brought in by the UK government at the start of 2022, which saw all eligible women in Wales have their wait times increased from three to five years in between tests. The government expects to roll out the policy in England this year after the pandemic caused the delay of its initial release. Experts insisted the move was safe, but campaigners hit back at the plans, arguing it would cause preventable deaths by delaying the detection of cancer or pre-cancerous issues.

In a statement to the Guardian, the UK’s Secretary for Patient Safety and Primary Care says it’s “great to see how this new research could help alert women who are at higher risk to help prevent breast, ovarian, womb, and cervical cancer before it starts.” Until this time, cancer screening remained vital and urged all women aged 25 and above to attend their appointments when invited. The secretary did not remark on the new government policy.

An ovarian cancer specialist urged caution in interpreting the data: They show a “moderate association” between the methylation signature and ovarian cancer, said Dr. Rebecca Stone, the Kelly Gynecologic Oncology Service director at Johns Hopkins Hospital. “They are not showing that it’s predictive or diagnostic,” Stone stressed. Clarifying that to see whether the cervical cell signature predicts cancer, a study would have to observe a large group of women over a long period.

Filling the gap in screening options for women

In contrast, Athena Lamnisos, CEO of the Eve Appeal, emphasizes the importance of a new screening tool:

“Creating a new screening tool for the four most prevalent cancers that affect women and people with gynae organs, particularly the ones which are currently most difficult to detect at an early stage, from a single test could be revolutionary.”

The Eve Appeal goes on that women could get separate risk scores for each of the four cancers in the future where medical teams could offer those with high scores more active monitoring, regular mammograms, risk-reducing surgery, or therapeutics.

Ultimately, it’s better to prevent than to treat, and this method could offer women worldwide access to proper screening services that could save lives through the application of early intervention and preventative medicine.

Study on mice: Exercising later in life can keep your muscles young

Exercising can not only make you feel younger, but it can also actually keep you younger as well. A study on mice suggests that exercising, even later in life, can do wonders for your muscles. In addition to underscoring the importance of staying active, the study could also help us uncover some of the secrets of rejuvenation.

Even though some diseases are inherited, we can still improve our overall health through lifestyle choices such as diet and exercise. Still, whatever the reason, the genes related to some of these conditions must be expressed for them to develop. So how does this happen?

A new study has brought us closer to an answer by mapping the genetic changes involved in rejuvenating the muscle cells of elderly mice put on an exercise program.

Turning genes on and off

The analysis centers on DNA, the “blueprint” for our bodies. DNA consists of four bases, called cytosine, guanine, adenine, and thymine, and the process used to help manage these massive helixes: a methyl molecule composed of one carbon and three hydrogen atoms. These atoms attach themselves to one of the four bases (cytosine) to form what’s known as a CpG site.

When this occurs, the CpG becomes methylated and the site produces proteins to regulate something in the body — whatever that something may be. In contrast, the region becomes unmethylated when you lose that methyl group, turning that gene off. In this way, a process called DNA methylation can promote or inhibit the expression of specific genes — whether it’s stopping a tumor, preventing cancer, or activating genes responsible for causing wrinkles in old age. This process is constant, occurring billions of times a second in every cell throughout the body, and we’re just starting to understand it.

DNA methylation is one of the many mechanisms of epigenetics, where inborn or acquired changes in DNA don’t touch the actual sequence – meaning a person can potentially reverse things like fat deposits through diet or exercise. More and more studies are starting to suggest that this is an unharnessed and robust process, linked to longevity and the regulation of lifespan in most organisms on earth.

The current study attempts to further this theory using lifestyle interventions such as exercise to roll back genetic aging in skeletal muscle – measuring the animal’s ‘epigenetic clock’ for accuracy. This clock is measured via methylation levels in the blood to reflect exposures and disease risks independent of chronological age, providing an early-warning system and a true representation of a period of existence.

Kevin Murach, an assistant professor at the University of Arkansas, says, “DNA methylation changes in a lifespan tend to happen in a somewhat systematic fashion. To the point, you can look at someone’s DNA from a given tissue sample and with a fair degree of accuracy predict their chronological age.”

Using exercise to turn back the clock

The study design was relatively simple: mice nearing the end of their natural lifespan, at 22 months, were given access to a weighted exercise wheel to ensure they built muscle. They required no coercion to run on the wheel, with older mice running from six to eight kilometers a day, mostly in spurts, and younger mice running up to 10-12 kilometers.

Results from the elderly mice after two months of weighted wheel running suggested they were the epigenetic age of mice eight weeks younger, compared to sedentary mice of the same maturity.

The team also used the epigenetic clock to map a multitude of genes involved in the formation and function of muscles, including those affected by exercise. Blood work indicated that the genes usually over methylated (hypermethylated) in old age resumed normal methylation in the active aged mice, unlike those mapped in their sedentary counterparts.

For instance, the rbm10 gene is usually hypermethylated in old age, disrupting the production of proteins involved in motor neuron survival, muscle weight & function, and the growth of striated muscle. Here it was shown to undergo less methylation in older mice who exercised, improving its performance. Normal methylation levels also resumed across the Timm8a1 gene, keeping mitochondrial function and oxidant defense at workable levels – even where neighboring sites exhibited dysfunctional epigenetic alterations.

More work is needed to harness DNA methylation

Murach notes that when a lifespan is measured incrementally in months, as with this mouse strain, an extra eight weeks — roughly 10 percent of that lifespan — is a noteworthy gain, further commending the importance of exercise in later life.

He adds: that although the connection between methylation and aging is clear, methylation and muscle function are less clear. Despite these sturdy results, Murach will not categorically state that the reversal of methylation with exercise is causative for improved muscle health. “That’s not what the study was set up to do,” he explained. However, he intends to pursue future studies to determine if “changes in methylation result in altered muscle function.”

And, “If so, what are the consequences of this?” he continued. “Do changes on these very specific methylation sites have an actual phenotype that emerges from that? Is it what’s causing aging or is it just associated with it? Is it just something that happens in concert with a variety of other things that are happening during the aging process? So that’s what we don’t know.”

He summarizes that once the medical community has mapped the mechanics of dynamic DNA methylation in muscle, their work could provide modifiable epigenetic markers to improve muscle health in the elderly. 

Scientists identify the specific gene that protects against severe COVID-19

Researchers from Karolinska University have discovered a gene that reduces the severity of Covid infections by 20%. In their paper the scientists state that this explains why the disease’s symptoms are so variable, hitting some harder than others.

Why do some people fall severely ill from COVID-19 while others don’t? In addition to risk factors like age or obesity and plenty of other environmental factors, it also comes down to our varying genetic makeup. Therefore, researchers across the globe have begun the mammoth task of mapping the genes involved in making people more susceptible to catching SARS-CoV-2 (COVID-19) and developing a severe infection.

These large-scale efforts have thrown up more than a dozen genomic regions along the human chromosome containing large clusters of genes associated with severe COVID-19. However, the specific causal genes in these regions are yet to be identified, hampering our ability to understand COVID-19’s often selective pathology.

Now, scientists build on these findings to pinpoint a gene that confers protection from critical illness.

Neanderthal DNA protects against severe COVID-19

The previous studies from 2020 concentrated on the genetic data of people of European ancestry recorded by multi-disciplinary teams all over the world for the 1000 Genomes Project. This monumental collaboration uncovered a specific segment of DNA known as the OAS1/2/3 cluster, which lowers the risk of developing an acute COVID-19 infection by 20%. Inherited from Neanderthals in roughly half of all people outside of Africa, this segment is responsible for encoding genes in the immune system.

The genetic array came about as a result of the migration of an archaic human species out of the African continent about 70,000 years ago who mated and mingled DNA with Neanderthals reproduced in their offspring’s haplotypes, a set of inheritable DNA variations close together along a chromosome. 

However, most human haplotypes outside Africa now include DNA from Neanderthals and Denisovans (an ancient human originating in Asia). Consequently, this ancient region of DNA is heaving with numerous genetic variants, making it challenging to distinguish the exact protective gene that could serve as a target for medical treatment against severe COVID-19 infection.

A possible solution is that people of African descent do not contain these archaic genes in their haplotypes, making them shorter and easier to decipher.

To test this theory, the researchers checked the 1000 Genomes project database for individuals carrying only parts of this DNA segment – focusing on individuals with African ancestry who lack heritage from the Neanderthals. Remarkably, the researchers found that individuals of predominantly African ancestry had the same protective gene cluster as those of European origin.

Genetic studies should be a multi-cultural affair

Once they established this, the researchers collated 2,787 COVID-19 cases with the genetic data of 130,997 individuals of African ancestry to reveal the gene variant rs10774671 G thought to convey protection against COVID-19 hospitalization. Their results correspond to a previous, more extensive study of individuals of European heritage, with analysis suggesting it is likely the only causal variant behind the protective effect.

Surprisingly, this previously ‘useless’ ancient variant was found to be widespread, present in one out of every three people of white European ancestry and eight out of ten individuals of African descent.

In evolutionary terms, the researchers write that the variant exists today in both these gene pools “as a result of their inheritance from the ancestral population common to both modern humans and Neanderthals.” Accordingly, their data adds more weight to the standard held theory that a common ancestor originated in Africa millions of years ago before sharing their DNA across the globe.

And while there’s much more to uncover regarding the newly discovered variant, the researchers can firmly suggest at this stage that the protective gene variant (rs10774671 G) works by determining the length of a protein encoded by the gene OAS1. As the longer version of the protein is more effective at breaking down the virus than the unaltered form, a life-threatening infection is less likely to occur.

Using genetic risk factors to design new COVID-19 drugs

Despite their promising results, the team cautions that the 1000 Genomes Project does not provide a complete picture of this genomic region for different ancestries. Nevertheless, it’s clear that the Neanderthal haplotype is virtually absent among individuals of primarily African ancestry, adding, “How important it is to include individuals of different ancestries” in large-scale genetic studies.

Senior researcher Brent Richards from McGill University says that it is in this way “we are beginning to understand the genetic risk factors in detail is key to developing new drugs against COVID-19.”

If these results are anything to go by, we could be on the cusp of novel treatments that can harness the immune system to fight this disease.

New COVID variant identified in France — but experts say we shouldn’t fear it

Scientists have identified a previously unknown mutant strain in a fully vaccinated person who tested positive after returning from a short three-day trip to Cameroon.

Academics based at the IHU Mediterranee Infection in Marseille, France, discovered the new variant on December 10. So far, the variant doesn’t appear to be spreading rapidly and the World Health Organization has not yet labeled it a variant of concern. Nevertheless, researchers are still describing and keeping an eye on it.

The discovery of the B.1.640.2 mutation, dubbed IHU, was announced in the preprint server medRxiv, in a paper still awaiting peer review. Results show that IHU’s spike protein, the part of the virus responsible for invading host cells, carries the E484K mutation, which increases vaccine resistance. The genomic sequencing also revealed the N501Y mutation — first seen in the Alpha variant — that experts believe can make COVID-19 more transmissible.  

In the paper, the clinicians highlight that it’s important to keep our guard and expect more surprises from the virus: “These observations show once again the unpredictability of the emergence of new SARS-CoV-2 variants and their introduction from abroad,” they write. For comparison Omicron (B.1.1.529) carries around 50 mutations and appears to be better at infecting people who already have a level of immunity. Thankfully, a growing body of research proves it is also less likely to trigger severe symptoms.

Like many countries in Europe, France is experiencing a surge in the number of cases due to the Omicron variant.

Experts insist that IHU, which predates Omicron but has yet to cause widespread harm, should not cause concern – predicting that it may fade into the background. In an interview with the Daily Mail, Dr. Thomas Peacock, a virologist at Imperial College London, said the mutation had “a decent chance to cause trouble but never really materialized. So it is definitely not one worth worrying about too much at the moment.”

The strain was first uploaded to a variant tracking database on November 4, more than two weeks before Omicron was sequenced. For comparison, French authorities are now reporting over 300,000 new cases a day thought to be mostly Omicron, with data suggesting that the researchers have identified only 12 cases of IHU over the same period. 

On the whole, France has good surveillance for COVID-19 variants, meaning health professionals quickly pinpoint any new mutant strains. In contrast to Britain, which only checks three in ten cases for variants. The paper’s authors state that the emergence of the new variant emphasizes the importance of regular “genomic surveillance” on a countrywide scale.

New gene-editing technology creates single-sex mice

A group of researchers at the Francis Crick Institute, working with the University of Kent, have used gene-editing technology to create male-only and female-only mice litters. The technology could avoid the destruction of hundreds of thousands of unwanted mice in the academic world, as either male or female mice are typically required. 

Image credit: Flickr / Nick Harris.

Whether we like it or not, there’s still a great deal of research that requires animal subjects. However, this demand isn’t uniform across genders. For any given task, there’s usually a demand for just male or female animals, not just in scientific research but also in farming.

Laboratory studies sometimes require only animals of the sex being studied, while in farming only female animals are needed for egg production and in dairy herds. That’s why it’s a common practice for animals of the undesired sex to be culled after birth. But that could change soon.

By deactivating a gene involved in the embryo development, the mice can be programmed to only form female embryos at an early stage of development, the researchers explained. This seems to work in experiments (with 100% accuracy), but the next step will be pilot studies, which will hopefully prove the feasibility of the method.

This could end up preventing millions of animals from being culled, having long-reaching implications, researchers say. It could be transformative — but it’s a form of animal eugenics, and we shouldn’t rush into it without discussing the implications at the society level.

“The implications of this work are potentially far-reaching when it comes to improving animal welfare, but should be considered at ethical and regulatory levels,” Peter Ellis, study author, said in a statement. “Before any use in agriculture, there would need to be extensive public conversation and debate, as well as changes to legislation.”

What’s behind this technology 

Sex chromosomes are behind whether a mammal turns out of male or female sex. Males have a Y chromosome from their father and an X chromosome from their mother, while females have two X chromosomes. In the study, the researchers found a way to deactivate a gene and prevent XX and XY mouse embryos from developing.

This is how it works. The team embedded one half of the gene-editing molecule, known as Crispr-Cas9, which deactivates the gene, into the father’s X or Y chromosome (depending on the sex needed) and the other into the mother’s DNA. This only works if both parts of Crispr-Cas9 are linked together, the researchers said.

“This method works as we split the genome editing process in half, between a male and female, and it is only when the two halves meet in an embryo through breeding, that it is activated. Embryos with both halves cannot develop beyond very early cell stages,” Charlotte Douglas, first author and scientist at the Crick, said in a statement. 

Surprisingly, the litter of the mice edited thusly didn’t turn out 2 times smaller (as you may expect with one of the sexes gone). Instead, litter sizes were around 30-40% smaller than the control litters. This happened because mice produce more eggs than needed. This would mean that when one sex is needed, fewer breeding animals would be required to produce the same number of offspring. 

The offspring that do survive only have half of the CRISPR-Cas9 elements within their genome. This prevents sex selection from being inherited by further generations – unless they are bred with an individual of the opposite sex that has the other half. It’s a different approach to “gene-drive” methods, which spread a mutation widely in a population.

It’s not the first time something like this has been proposed. Billions and billions of male chicks are slaughtered each year, as only females are useful for egg-laying, and researchers are developing ways to select the sex of chick embryos. 

The study was published in the journal Nature Communications. 

We’re getting a better idea of how moles turn into melanoma, and environment is key

New research is upending what we knew about the link between skin moles and melanoma.

Image via Pxhere.

Moles and melanomas are both types of skin tumors, and they originate from the same cells — the pigment-producing melanocytes. However, moles are harmless, and melanomas are a type of cancer that can easily become deadly if left untreated. The close relationship between them has been investigated in the past, in a bid to understand the emergence of melanomas.

New research at the Huntsman Cancer Institute (HCI) , the University of Utah, and the University of California San Francisco (UCSF) comes to throw a wrench into our current understanding of that link. According to the findings, our current “oncogene-induced senescence” model of the emergence of melanomas isn’t accurate. The research aligns with other recent findings on this topic, and propose a different mechanism for the emergence of skin cancer.


“A number of studies have challenged this model in recent years,” says Judson-Torres. “These studies have provided excellent data to suggest that the oncogene-induced senescence model does not explain mole formation but what they have all lacked is an alternative explanation — which has remained elusive.”

Melanocytes are tasked with producing the pigments in our skin which protect us from harmful solar radiation. Changes (mutations) in one specific gene in the genome of melanocytes, known as BRAF gene mutations, are heavily associated with moles; such mutations are found in over 75% of skin moles. At the same time, BRAF gene mutations are encountered in 50% of melanoma cases.

Our working theory up to now — the oncogene-induced senescence– was that when melanocytes develop the BRAFV600E mutation, it blocks their ability to divide, which turns them into a mole. However, when other mutations develop alongside BRAFV600E, melanocytes can start dividing uncontrollably, thus developing into cancer.

The team investigated mole- and melanoma tissues donated by patients at the UCSF Dermatology clinic in San Francisco or the HCI Dermatology clinic in Salt Lake City. Their analysis revolved around two methods known as transcriptomic profiling and digital holographic cytometry. The first one allows them to determine molecular differences between the cells in moles and those in melanomas. The second one was used to track changes inside individual cells.

“We discovered a new molecular mechanism that explains how moles form, how melanomas form, and why moles sometimes become melanomas,” says Judson-Torres.

The team reports that melanocytes don’t need to have mutations besides BRAFV600E to morph into melanoma. What does play a part, however, are environmental factors, transmitted to the melanocytes through the skin cells around them. Depending on exactly what signals they’re getting from their environment, melanocytes express different genes, making them either stop dividing or divide uncontrollably.

“Origins of melanoma being dependent on environmental signals gives a new outlook in prevention and treatment,” says Judson-Torres. “It also plays a role in trying to combat melanoma by preventing and targeting genetic mutations. We might also be able to combat melanoma by changing the environment.”

The authors hope that their findings will help researchers get a better idea of the biomarkers that can predict the emergence of melanoma at earlier stages than possible today. Furthermore, the results here today can also pave the way to more effective topical medicine that can prevent melanoma, or delay its progress.

The paper “BRAFV600E induces reversible mitotic arrest in human melanocytes via microrna-mediated suppression of AURKB” has been published in the journal eLife.

We’ve identified the genetic roots of OCD, pointing the way towards new treatments

New research led by the Vagelos College of Physicians and Surgeons, Columbia University, has linked certain patterns of genetic mutation to obsessive-compulsive disorder (OCD) in humans.

Image credits Benjamin Watson / Flickr.

The findings confirm that targeting certain genes can be a valid avenue for treatment against OCD, which affects between 1% to 2% of the population. We’ve known that there is a genetic component to this disorder, as it often runs in the family, but the causes of OCD had remained elusive so far.

Genes made me do it

“Many neurological diseases are influenced by strongly acting mutations which can cause disease by themselves,” says David Goldstein, PhD, director of the Institute for Genomic Medicine at Columbia and a senior author on the new paper.

“These mutations are individually very rare but important to find because they can provide a starting point for the development of therapeutics that target precise underlying causes of disease.”

Previous work on this topic had used a “candidate gene” model, the authors explain, in which researchers focus on particular genes they believe might be involved in a certain pathogenesis — in this case, OCD. While there was some success, such approaches can also miss important genes or lead to errors in statistical interpretation of our data. In other words, it can miss parts of the story and shift our overall understanding of what causes a condition.

However, there has been a recent shift towards genome-wide analyses in this field, the team explains. In short, this approach looks at all genes in a genome at the same time, checking each of them for evidence that they’re increasing the risk of developing OCD.

In collaboration with researchers from the Johns Hopkins University’s psychiatry department, the team used this genome-wide approach to identify relevant genes in the genomes of a cohort of over 1,300 OCD patients. They compared their sequences to a similar group of control participants. Scientists from the University of North Carolina at Chapel Hill, the David Geffen School of Medicine in Los Angeles, Harvard Medical School, and SUNY Downstate Medical Center in Brooklyn were also involved in the study.

They found a strong correlation between OCD and several rare mutations, but one in particular — of a gene called SLITRK5 — seemed to have the strongest association. This gene had also been identified in previous candidate-gene studies for OCD. However, the results of this study are much more reliable and the authors hope they will spur further research and development in drugs targeting the gene.

“When you look at genes that do not tolerate variation in the human population, those are the genes most likely to cause disease, and with OCD, we see an overall increased burden of damaging mutations in those genes compared to controls,” Goldstein says. “That’s telling us that there are more OCD genes to be found and where to find them.”

OCD is a condition that causes patients to have uncontrollable, recurring, and intrusive thought patterns and behaviors. It isn’t what we typically call OCD, such as the minor need to straighten a stack of books. In some, the compulsions are so severe that the person has an impending sense of dread until an action, whatever it may be, is completed. This can lead to a person spending twenty minutes opening and closing a door until they feel it has locked correctly — which is to say, it can heavily interfere with a patient’s daily life. OCD is also relatively common, affecting between 2-3% of US adults, which is twice as much compared to conditions such as schizophrenia.

Currently-available treatment avenues include serotonin reuptake inhibiting drugs and cognitive-behavioral therapy. Both are highly effective when they work, but around half of patients are resistant to either or both. A treatment that targets the genetic roots of OCD would thus be very welcome and useful for patients and doctors both.

The paper “. Exome sequencing in obsessive–compulsive disorder reveals a burden of rare damaging coding variants” has been published in the journal Nature Neuroscience.

We’ve identified a gene variant that seems to make people immune to the effects of COVID — but not to catching the virus

Researchers in the UK are closing in on a possible genetic defense against COVID-19. The findings could help explain why some people can catch the virus without getting sick.

A team of researchers led by members at the Newcastle University, UK, reports that the gene HLA-DRB1*04:01 likely confers its bearers some sort of protection against the coronavirus, or at least, from its more severe symptoms. This conclusion was drawn from the observation that the gene is found, on average, three times as often in asymptomatic patients compared to symptomatic ones.

The study worked with patients from the same communities in the UK in order to limit the influence of other factors such as environment, location, and socioeconomic status.

Genetically insulated

According to the authors, this is the first clear evidence of genetic resistance against COVID-19. While previous research has worked with whole genomes, that approach is far less effective than focusing on individual genes, as the current paper does. A genome-wide view can miss important tidbits of information, quite like watching the forest means you don’t focus on individual trees. The current research focused on comparing symptomatic to asymptomatic members of the same community to make it easier to spot how individual genes or alleles (variations of the same gene) can help protect us from COVID-19.

HLA-DRB1*04:01, a human leukocyte antigen gene, was identified as a prime candidate in this regard. The finding is based on samples taken from 49 patients with severe COVID-19 symptoms — who had been hospitalized with respiratory failure, — 69 hospital workers who had tested positive for the virus but were asymptomatic, and a control group.

These samples were analyzed so that the team could study the different HLA alleles present in the general population of North East England during the first lockdown. The asymptomatic patients, on average, were three times as likely to have the HLA-DRB1*04:01 allele in their genomes than symptomatic patients (16.7% vs. 5.1% after adjustment for age and sex).

From previous research, we know that the incidence of the HLA-DRB1*04:01 allele in the general population is directly correlated to latitude and longitude. People in the North and West of Europe are more likely to have this allele. Sadly, this also means that these areas will have a harder time keeping the virus under control.

“This is an important finding as it may explain why some people catch Covid but don’t get sick,” explains Dr. Carlos Echevarria from the Translational and Clinical Research Institute, Newcastle University, a Respiratory Consultant in the Newcastle Hospitals NHS Foundation Trust, and co-author of the paper. “It could lead us to a genetic test which may indicate who we need to prioritize for future vaccinations.”

“At a population level, this is important for us to know because when we have lots of people who are resistant, so they catch Covid but don’t show symptoms, then they risk spreading the virus while asymptomatic.”

Populations of European descent, the authors add, are most likely to remain asymptomatic but still carry and transmit the disease to individuals that do not enjoy the same levels of genetic protection. The fact that there is a link between gene expression and geolocation is a well-established scientific concept. Genes are selected for by the unique sets of demands placed on different groups by their environment, so people living in different areas will evolve different types of genetic defences. The HLA gene is no different: they develop over generations as a response to pathogens.

“Some of the most interesting findings were the relationships between longitude and latitude and HLA gene frequency,” adds co-author David Langton, whose company ExplantLab helped fund the study. “It has long been known that the incidence of multiple sclerosis increases with increasing latitude. This has been put down in part to reduced UV exposure and therefore lower vitamin D levels. We weren’t aware, however, that one of the main risk genes for MS, that is DRB1*15:01, directly correlates to latitude.”

“This highlights the complex interaction between environment, genetics and disease. We know some HLA genes are vitamin D responsive, and that low vitamin D levels are a risk factor for severe COVID and we are doing further work in this area.”

Still, the team notes that more studies will be needed (both in the UK and other areas) as there may be different copies of the HLA genes providing resistance in other populations.

The paper “The influence of HLA genotype on the severity of COVID‐19 infection” has been published in the journal HLA.

Different cities have their own microbial fingerprint, a global study reports

An international team of researchers says that every city has its own fingerprint — in the shape of pathogens.

Image credits Denis Poltoradnev.

The largest ever genetic study of urban microbiomes (including both surfaces and the air in 60 cities worldwide) reports that each city has its own microbial fingerprint. The project sequenced and analyzed samples from public transit systems and hospitals in cities around the world, identifying thousands of viruses, bacteria, and two archaea not found in reference databases.

Roughly 4,730 different samples, taken from cities on six continents over the course of three years were used as part of this study, the team explains. The analysis also revealed a set of 31 species that were found in 97% of the samples.


“Every city has its own ‘molecular echo’ of the microbes that define it,” says senior author Christopher Mason, a professor at Weill Cornell Medicine (WCM) and the director of the WorldQuant Initiative for Quantitative Prediction.

“If you gave me your shoe, I could tell you with about 90% accuracy the city in the world from which you came.”

This study is the first systematic, worldwide catalog of urban microbial ecosystems, according to the authors. Despite the breadth of the results here, the team is confident that any subsequent sampling of this kind will continue to find new species.

The paper draws its roots in 2013, when Mason started collecting and analyzing microbial samples in the New York City subway system. After publishing his findings, Mason was contacted by other researchers from around the world who wanted to perform similar analyses in their own cities. So he worked out a protocol that they could follow, posting it on YouTube. Samples were to be collected using DNA- and RNA-free swabs and sent to a lab at WCM for analysis along with controls. Most of the analysis part was handled by an Extreme Science and Engineering Discovery Environment (XSEDE) supercomputer in Pittsburgh.

Two years later, in 2015, Mason created the International MetaSUB (Metagenomics and Metadesign of Subways and Urban Biomes) Consortium to better handle all the data people were sending him. Samples from air, water, and sewage were now coming in from across the world in addition to those from hard surfaces.

Such genomic studies can help detect outbreaks of both known and unknown infections and can help us keep tabs on the levels of antibiotic-resistant microbes in different urban environments. It’s also a very useful tool when analyzing the evolution of microbial life.

“There are millions of species on Earth, but we have a complete, solid genome reference for only 100,000 to 200,000 at this point,” Mason says, explaining that the discovery of new species can help with the building of microbial family trees to see how different species are related to one another.

“Based on the sequence data that we’ve collected so far, we’ve already found more than 800,000 new CRISPR arrays,” he says. Additionally, the findings indicate the presence of new antibiotics and small molecules annotated from biosynthetic gene clusters (BGCs) that have promise for drug development.

These samples led to the results published in this paper: 4,246 known species of microorganisms were identified worldwide, 31 of which were present in 97% of all samples from urban areas.

“One of the next steps is to synthesize and validate some of these molecules and predicted  biosynthetic gene clusters (BGCs), and then see what they do medically or therapeutically,” Mason says. “People often think a rainforest is a bounty of biodiversity and new molecules for therapies, but the same is true of a subway railing or bench.”

The paper “”A global metagenomic map of urban microbiomes and antimicrobial resistance” has been published in the journal Cell.

Genetically modified grass saves soils destroyed by military target practice

A common species of prairie grass can help clean soils of dangerous chemicals released by military-grade compounds, a new paper reports. The only catch (at least, in the eyes of some), is that we need to genetically modify it for the task.

A plot of switchgrass. Image credits Great Lakes Bioenergy Research Center / Flickr.

Genetically modified (GM) switchgrass (Panicum virgatum) can be used to purge soils of RDX residues, according to new research. RDX belongs to the nitramide chemical family, is flavorless, odorless, and extremely explosive. Pound for pound, it’s more powerful than dynamite. Given its high stability and ability to explode hard, RDX was in use in military-grade munitions during (and since) WW2. You’ve probably heard of C-4; RDX is its main component, alongside some plasticizing agents.

One downside of using RDX on a wide scale (that, admittedly, wouldn’t factor in very much during an active conflict) is that it can be quite damaging to the environment. In particular, compounds produced by RDX after it detonates (in combat or in firing ranges) spread around the point of impact and accumulate in groundwater, where they can pose a very real threat to any humans or wildlife they come into contact with. RDX stored in munition dumps, buried in minefields, or in rounds discarded improperly will also leech such compounds into their environment.

Genetically modified help

However, one species that’s traditionally employed against soil erosion can be modified to remove these compounds from the soil. The study, led by members at the University of York, has shown that this approach has promise at least when talking about the land on live-fire training ranges, munitions dumps, and minefields. Theoretically, however, it should be applicable wherever switchgrass can grow.

“The removal of the toxic RDX from training ranges is logistically challenging and there is currently a lack of cost-effective and sustainable solutions,” explains Dr. Liz Rylott from the Department of Biology and Director of the Centre for Novel Agricultural Products (CNAP), co-author of the study.

“Our research demonstrates how the expression, in switchgrass, of two bacterial genes that have evolved specifically to degrade RDX gives the plants the ability to remove and metabolize RDX in the field at concentrations relevant to live-fire military ranges. We demonstrated that by inserting these genes into switchgrass, the plant then had the ability to degrade RDX to non-detectable levels in the plant tissue.”

RDX-bearing ammo is still commonly used at firing ranges for training purposes, and has been for several decades already. This has led to high and widespread levels of groundwater contamination around such sites, which is never good news.

The authors explain that their approach involved grafting two genes from bacteria that are known to break down RDX into switchgrass. These plants — essentially GMOs at this point — were then grown on contaminated soil at one US military site. The plants grew well and had degraded the targeted compounds below detectable in their own tissues levels by the end of the experiment.

All in all, the grass degraded RDX at a rate of 27 kgs per hectare, which isn’t bad at all. According to the team, this is the most successful attempt to use plants to clean organic pollutants in the field to date. Processes that use plants for this purpose are collectively known as phytoremediation, and they’re a subset of the greater field of bioremediation, which involves the use of any type of organism or biological process for this task.

The findings here are of particular interest as organic pollutants, in general, tend to interact heavily with their environment (meaning they cause quite a lot of damage) while also being resistant to natural degradation processes (meaning they last for a long time in the wild). RDX in particular is of growing concern in the US. The Environmental Protection Agency (EPA) has it designated as a priority pollutant, with more than 10 million hectares of military land in the US being contaminated with weapons-associated compounds, RDX making up a sizable chunk of that contamination.

“The recalcitrance of RDX to degradation in the environment, combined with its high mobility through soil and groundwater, mean that plumes of toxic RDX continue to spread below these military sites, threatening drinking water supplies,” explains Professor Neil Bruce, also from CNAP, the study’s corresponding author.

One example the paper cites is that plumes of RDX pollution were found in groundwater and aquifers beneath the Massachusetts Military Reservation training range in Cape Cod back in 1997. This aquifer was, in effect, the only source of drinking water for half a million people, and the discovery prompted the EPA to ban the use of all live ammo during training at this site.

The paper “Field trial demonstrating phytoremediation of the military explosive RDX by XplA/XplB-expressing switchgrass” has been published in the journal Nature Biotechnology.

Living fossil fish has 62 copies of a “parasite gene” humans share too — we have no idea how they got there

The capture of a ‘living fossil’ fish off the coast of South Africa in the 1930s is now helping us understand one of the more exotic ways evolution can happen — interspecies genetic hijacking.

A model of Latimeria chalumnae, one of two known species of coelacanths. Image via Wikipedia.

Coelacanths are one of the oldest lineages of fish in existence today. They’re so old, in fact, that they’re more closely related to the ancestors of reptiles and amphibians than modern-day fish. We first encountered them as fossils from the Late Cretaceous (some 66 million years old), and naturally assumed they must’ve died off by now. However, the capture of a live African Coelacanth (Latimeria chalumnae) fish in 1938 showed that it was actually still living in the deep oceans, and had hardly changed compared to its fossilized relatives.

But we should never judge a fish by its scales, as new research explains that the species did in fact gain 62 new genes around 10 million years ago. The most interesting part is how — these didn’t appear spontaneously in their genomes but are ‘parasitic’ DNA gained through encounters with other species.

Genetic stowaways

“Our findings provide a rather striking example of this phenomenon of transposons contributing to the host genome,” says Tim Hughes, senior study author and a professor of molecular genetics in the Donnelly Centre for Cellular and Biomolecular Research at the University of Toronto.

“We don’t know what these 62 genes are doing, but many of them encode DNA binding proteins and probably have a role in gene regulation, where even subtle changes are important in evolution.”

Coelacanths have earned the moniker of “living fossils” because they share so much of their anatomy with the fossilized specimens — in fact, they’re pretty much identical from a physical point of view. But the current findings showcase how gene transfer between species (through elements known as transposons or “jumping genes”) can shape evolution and, perhaps, even alter the genetic trajectory of entire species or lineages.

Transposons are genes that use a self-encoded enzyme to recognize themselves. This enzyme can then cut them out of the genetic strand and paste them in somewhere else. Sometimes, this process can interact with the cell division process and generate new copies of the transposon.

Still, nothing lasts forever, and eventually, the information describing the enzyme degrades. At this point, the transposon can no longer move throughout the code, but it’s still there and acts like any other gene. If it confers some kind of advantage to the host organism, it can be selected for over time through evolutionary processes and become part of their genetic lineage. Coelacanths aren’t by any means the only animals we’ve seen such ‘parasite’ genes in, but they do have a very high number of such genes.

“It was surprising to see coelacanths pop out among vertebrates as having a really large number of these transposon-derived genes because they have an undeserved reputation of being a living fossil,” says graduate student Isaac Yellan who spearheaded the study.

“The Coelacanth may have evolved a bit more slowly but it is certainly not a fossil.”

The team was actually studying counterparts of a human gene, CGGBP1, in other species. We knew that this was a legacy of a particular transposon in the common ancestor of mammals, birds, and reptiles. During their work, the team found CGGBP-like genes in some but not all fish species they studied, and one type of fungus. Worms, molluscs, and most insects had none. But the Coelacanth (whose genome was sequenced in 2013) had 62.

As a common ancestry was out of the question, the team concluded that these transposons entered various lineages at various times in history through horizontal gene transfer. We don’t exactly know where they came from, but one known documented source of such transfers are parasites. This would also explain why the gene was introduced in the fish’s genome several times.

We still don’t know what these genes do. Lab experiments showed that the protein they encode binds to unique sequences of DNA, so they could be involved in gene regulation, like their human counterpart. Their origin however is still a mystery.

Given the extreme rarity of living specimens — the only other living species ever found, Latimeria menadoensis, was discovered in 1998 after being pulled by a fishing boat and winding its way into an Indonesian market. These two species split before the genes were introduced.

The paper “Diverse Eukaryotic CGG Binding Proteins Produced by Independent Domestications of hAT Transposons” has been published in the journal Molecular Biology and Evolution.

PTSD seems to be tied to gene expression changes in the brain

Researchers are shedding new light on the origins of PTSD, post-traumatic stress disorder.

Image via Pixabay.

Post-mortem analysis of the brain tissue of patients who had been diagnosed with PTSD are helping us better understand the condition. There’s still a lot we can’t make sense of with PTSD, including why women seem to be more susceptible to it, and whether an impaired immune system plays a part.

The brain of the matter

The analysis was led by researchers from the Yale University, finding differences in gene expression patterns between patients with PTSD and healthy people in four regions of the prefrontal cortex (PFC). The PFC is associated with higher cognitive functions. These differences affected two types of cells in patients: interneurons, which inhibit neural activity, and microglia, immune system cells in the central nervous system, the researchers report.

“The findings suggest that together these changes might contribute to an impaired ability to respond to traumatic stress,” said Matthew Girgenti, a research scientist in the Yale Department of Psychiatry and lead author of the study.

Some 8% of the world’s population has been diagnosed with PTSD at one point or another, the authors explain. Among those who have experienced severe stress such as combat, natural disasters, assault, roughly 35% will show symptoms of PTSD. These include intrusive, distressing memories of the traumatic event, hyperarousal upon exposure to stimuli related to the traumatic event, or avoidance of others.

Most of the types of cells heavily impacted by PTSD were the same in men as well as women. The genders however differed in where exactly in the brain affected genes were being expressed. This may be the root of why women are almost twice as likely to develop PTSD and other anxiety disorders as men, and why their symptoms tend to be more severe, the authors explain.

Although almost half of the patients studied by the team were also diagnosed with some form of depression, gene expression patterns in their brains were only loosely tied with depression. They were much more closely linked biologically with schizophrenia and bipolar disorder

“This is a new beginning for the PTSD field,” noted John Krystal, a Professor at Yale and co-senior author of the paper. “We need new treatments for PTSD, and studies like this will provide the scientific foundation for a new generation of medication development efforts.”

The paper “Transcriptomic organization of the human brain in post-traumatic stress disorder” has been published in the journal Nature Neuroscience.

Scientists sequence genome of Fleming’s original penicillin-producing fungus

A group of researchers successfully sequenced the genome of the mold that produced penicillin, the world’s first true antibiotic, using samples frozen alive more than fifty years ago. The team compared Alexander Fleming’s original sample of penicillium mold to two strains of mold now used to produce the substance today.

The freeze-dried Fleming strain from which the Penicillium fungus was grown and genome sequenced. Credit CABI.

Back in 1928, biologist Alexander Fleming noticed Penicillium mold growing in a culture of Staphylococcus aureus he was studying. It appeared the experiment was wrecked but Fleming noticed that where the mold grew, the bacteria didn’t. He later identified the chemical compound that was fatal to the bacteria and called it penicillin in honor of the humble mold.

Fleming froze samples of the mold that produced his first isolated samples of pure penicillin. More than 50 years later, a group of researchers at Imperial College London and the University of Oxford decided to look them up. They compared the samples with the genomes of two modern strains of Penicillium mold, now used in the United States.

“We originally set out to use Alexander Fleming’s fungus for some different experiments, but we realized, to our surprise, that no one had sequenced the genome of the original Penicillium, despite its historical significance to the field,” said Timothy Barraclaugh, co-author, in a statement.

The researchers found a subtle difference between the two genomes, which might help us better combat antibacterial resistance. Most antibiotics are based on chemicals that fungi or bacteria produce to defend themselves. If you get a dose of penicillin, it was likely produced by mold cultures, which are descendants of samples taken from moldy cantaloupes.

Over the years, antibiotics manufacturers bred their cantaloupe mold cultures to produce more penicillin. This means the genomes of modern industrial Penicillum mold are probably very different from their cantaloupe-eating ancestors.

The team looked at two sets of genes in particular. The ones that coded for chemicals called enzymes and the ones that control how much of an enzyme to make and when. They found that modern strains had more copies of the genetic instructions for making those enzymes, which meant those cells would make more enzymes and thus more penicillin.

While nature favors the traits that make mold more likely to survive and pass on its genes, artificial selection by humans cares about penicillin production over everything else. But Fleming’s mold and the modern strains used different versions of the enzymes that make penicillin. This could be due to evolution in the lab or because the strains are from different continents and evolved different enzymes.

If that’s the case, those different enzymes might produce different versions of penicillin. Still, there’s not enough data now to say exactly how the different enzymes impact the final product. The difference could lead to more efficient penicillin production, more effective penicillin, or a way to work around at least some of the resistance certain bacteria strains have evolved to the drug, the researchers believe.

“Industrial production of penicillin concentrated on the amount produced, and the steps used to artificially improve production led to changes in numbers of genes,” Ayush Pathak, lead author, said in a statement. “But it is possible that industrial methods might have missed some changes for optimizing penicillin design, and we can learn from natural responses to the evolution of antibiotic resistance.”

The study was published in the journal Scientific Reports.

Millions of genetically-modified mosquitoes will be deployed to save Floridians from bites

Florida will become home to 750 million genetically-modified mosquitoes. Local authorities have approved the release of these insects in a bid to bring down the numbers of local mosquito swarms.

Image via Pixabay.

Mosquitoes suck — more to the point, they suck our blood. Not only is this really annoying and itchy, it can also be dangerous: mosquitoes are carriers of diseases like dengue fever and Zika, which they spread by coming into contact with the blood in our veins.

Engineered to fail

Aedes aegypti, the most common type of mosquito and so the one most likely to be biting you in your sleep, is in fact an invasive species in Florida. They’re typically found near standing pools of water, where they lay their eggs and spend their larval days.

Because nobody has much love for them, we’ve come to rely on pesticides to keep them away or, ideally, very dead. But the insects have developed a resistance to such compounds.

In order to keep their numbers in check, Florida officials have approved the release of around 750 million genetically-modified mosquitoes into the wild. All these mosquitoes, known as OX5034, are males, and carry a special gene that will kill off any female offspring they have. Since only female mosquitoes need to bite for blood (which they use as nutrients for eggs), this would dramatically limit the threat they pose to public health.

This decision comes after the US Environmental Agency granted permission to Oxitec, a British-based company operated in the US, to produce these modified mosquitoes.

The approval of this release was not without its critics. Environmental groups warn that we don’t know enough about how such mosquitoes behave in the wild to know for sure that it’s safe to release them. Their biggest worries are the creation of hybrids between wild and modified mosquitoes, and possible damage to the ecosystems that these insects are part of. An online petition on Change.org that plans to stop the US being “a testing ground for these mutant bugs” has also gathered nearly 240,000 signatures so far.

Oxitec rebuts that the issue has been studied amply and that the release should go without a hitch. Either way, the insects are set to be released in 2021 in the Florida Keys islands.

This isn’t the first time that modified mosquitoes have been used to try and control wild populations. They were previously also used in Brazil to combat Zika, and Oxitec said the results of that experiment were “positive”. It plans to also deploy the mosquitoes in Texas beginning sometime next year — although the company hasn’t gotten state or local approval as yet, it did receive the green light on the federal level.

“We have released over a billion of our mosquitoes over the years. There is no potential for risk to the environment or humans,” an Oxitec scientist told AP news agency.

New study furthers our understanding of how genetics influence heavy drinking

A new study comes to flesh out our understanding of the genetic basis for problematic drinking.

Image via Pixabay.

Previously, we knew of 13 gene variants associated with heavy drinking. Now, this study expands our knowledge to an impressive 29 different gene variants linked to problematic alcohol use. One limitation of the study is that, despite its relatively large sample of 435,000 people, all of them were of European descent.

Bottoms up

“The new data triple the number of known genetic risk loci associated with problematic alcohol use,” said Joel Gelernter at Yale University School of Medicine, the Foundations Fund Professor of Psychiatry and a professor of genetics and neuroscience.

Foundations Fund Professor of Psychiatry and professor of genetics and of neuroscience, who is the senior author of the multi-institutional study.

The study looked at genome-wide records of people of European ancestry contained in four separate biobanks and datasets. The team identified individuals who met criteria for problematic drinking, including alcohol use disorder and alcohol use with medical consequences and then looked for genetic variants they all shared.

They located 19 previously-unknown genes that represent risk factors for such behavior, alongside 10 previously-identified genes.

Furthermore, they looked at genetic risk factors for several psychiatric disorders including anxiety disorder and depression in the genomes. During the study, this step allowed them to analyze the genetic links between such disorders and heavy drinking. Major depressive disorder showed the greatest correlation to problematic drinking; risk-taking behavior, insomnia were also positively correlated with such behavior.

The genes identified in this study are particularly stable from a hereditary point of view in the brain (they’re more stable across generations) and in “evolutionarily conserved regulatory regions of the genome”, which suggests that they perform important functions in our metabolism. Exactly what these functions remain to be determined.

“This gives us ways to understand causal relations between problematic alcohol use traits such as psychiatric states, risk-taking behavior, and cognitive performance,” said Yale’s Hang Zhou, associate research scientist in psychiatry and lead author of the study. “With these results, we are also in a better position to evaluate individual-level risk for problematic alcohol use,” Gelernter said.

Heavy drinking is associated with adverse medical and social outcomes, so understanding which people are at risk for such behavior could help us better protect them.

The paper “Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits” has been published in the journal Nature Neuroscience.

Researchers reprogram cells to build artificial structures

Researchers at Stanford have figured out a way to reprogram cells to build synthetic structures for various uses inside the body using synthetic materials.

Image credits Jia Liu et al., (2020), Biotech.

The research is based on a new technique developed by the team, which they call genetically targeted chemical assembly, or GTCA. Through the use of GTCA, they were able to construct artificial structures in mammalian and C. elegans (a worm used as a model organism) neurons out of two biocompatible materials — an insulator and a conductor.

New build order

“We turned cells into chemical engineers of a sort, that use materials we provide to construct functional polymers that change their behaviors in specific ways,” said Karl Deisseroth, professor of bioengineering and of psychiatry and behavioral sciences, who co-led the work.

“We’ve developed a technology platform that can tap into the biochemical processes of cells throughout the body,” says study co-leader Zhenan Bao.

The team focused on brain cells or neurons, but they are confident that GTCA will work on other types of cells as well.

They began by genetically modifying the cells, using standard bioengineering techniques to insert the genes encoding the enzyme APEX2 into specific neurons. The next step involved submerging the worms and tissues in a solution of diluted hydrogen peroxide and particles of the two materials that the cells would employ.

The hydrogen peroxide was needed as it triggers a series of chemical reactions in cells with the APEX2 gene that polymerizes — ties together — the particles of raw material. The end products were mesh-like weaves wound around the cells that were either conductive or insulating. Depending on the electrical properties of this mesh, the neurons’ activity was amplified (they ‘fired’ signals more often) or dampened (making them fire more slowly). The team ran the experiment with slices of living mouse brain and on cultures of neurons (also harvested from rat brains) and, after testing the properties of the polymer meshes, they also tested to see if the solution was toxic to the cells upon being injected — it wasn’t.

The team doesn’t have medical applications in mind for their research so far, saying instead that it is a “tool for exploration”. However, the findings could have massive implications for the study of multiple sclerosis, a debilitating condition that stems from the breakdown of (myelin) insulation around neurons. Conductive polymer meshes may also help in the treatment of conditions such as epilepsy, but it’s still too early to tell.

In the future, the team plans to expand on the range of materials that can be used with their method and improve the “possibilities [of] this new interface of chemistry and biology,”

The paper “Genetically targeted chemical assembly of functional materials in living cells, tissues, and animals” has been published in the journal Science.

Famous Harvard scientist creates dating app that matches for genetic compatibility

George Church. Credit: Wikimedia Commons.

Harvard biologist George Church, one of the pioneers of the Human Genome Project and gene editing, received quite a bit of bad press after he admitted to receiving funds from Jeffrey Epstein. But, in a recent interview with CBS’ 60 Minutes, Church made another shocking revelation: he’s working on a genetics-based dating app, which many people see as treading on dangerous territory.

Those genes are hot

Church’s research is focused on reversing aging, making humans immune to viruses, and eradicating genetic diseases. Perhaps all of this time in the lab may have clouded Church’s judgment, who’s latest project is a dating app where you can only right swipe on people who match certain genes. The idea is to pair people based on the propensity of their genes, so there would be fewer children suffering from hereditary diseases.

Does that sound sexy? Well, that sounds more like a right swipe on eugenics to me. Historically, eugenicists advocated selective breeding to improve the genetic composition of the human race. Any discussion on eugenics eventually tangents into the WWII Nazi goal of cultivating a master race, which also led to the Holocaust and the extermination of millions.

During Church’s interview, the geneticist spoke about some of his latest projects, such as experiments that use Church’s own DNA to grow organs in the lab.

He also told CBS correspondent Scott Pelley that he regretted accepting money for his research from Jeffrey Epstein, a convicted pedophile, saying that he was sorry for “not knowing more about the donor.”

Epstein, who has long boasted of his scientific philanthropy and association with academics like Stephen Hawking, had some idea about genetics as dubious as his sexual predatory ways. He reportedly wanted to inseminate 20 women at a time inside his 33,000-square-foot Zorro Ranch in Stanley, New Mexico, much like cattle stock, in order to propagate his own genome.

The most shocking segment from the CBS interview was Church’s dating app — which is currently in development but with no other details released to the public.

“You wouldn’t find out who you’re not compatible with. You’ll just find out who you are compatible with,” Church said.

“You’re suggesting that if everyone has their genome sequenced and the correct matches are made, that all of these diseases could be eliminated?” 60 Minutes’ Scott Pelley asked.

“Right. It’s 7,000 diseases. It’s about 5% of the population. It’s about a trillion dollars a year, worldwide,” Church said. 

Ironically, if Church used his own app, he wouldn’t be the most eligible bachelor. The biologist has dyslexia, attention deficit disorder, and narcolepsy, which should render him an incompatible match to many.

“If somebody had sequenced your genome some years ago, you might not have made the grade in some way,” Pelley said.

“I mean, that’s true,” Church replied. “I would hope that society sees the benefit of diversity, not just ancestral diversity, but in our abilities. There’s no perfect person.”

Church was poor with details but there are many things we’d like to know. What kind of genetic diseases will people be screened for and what would an algorithm that ranks people for their genetic superiority look like?

Researchers sequence DNA of coral and their associated organisms

Research from The University of Queensland and James Cook University is looking into which genes allow corals to make friends with algae and bacteria.

Image via Pixabay.

Corals work together with microscopic organisms, establishing symbiotic relationships that benefit both parties. While we’ve been aware of this for some time now, we didn’t understand the biochemical mechanisms that underpin this collaborative predisposition. A new study is shedding light on the subject.

Coral secrets

“Symbiotic relationships are incredibly important for thriving corals,” says Dr. Steven Robbins, the paper’s lead author. “The most striking example of this is coral bleaching, where corals expel their algal symbiotic partners at higher-than-normal water temperatures.”

Corals partner up with algae and bacteria to make ends meet. The coral fishes raw material out of the water and provides housing, and, in return, the algae keeps everyone well fed and plump. Certain stressors, however — especially sustained, excessive heat — can cause a falling out between the two partners, i.e. bleaching. Judging by how well they work together, such a ‘breakup’ is undeniably bad for both, and we know for a fact that coral reefs suffer extensive damage as a result of bleaching episodes.

Dr. Robbins says that the findings further our understanding of these collaborations, and can aid in conserving or perhaps even healing the world’s coral reefs.

“As algae make up the bulk of the coral’s food through photosynthesis, the coral will die if temperatures don’t cool enough to allow symbiosis to re-establish,” he explains. “It’s possible that equally important interactions are happening between corals and their bacteria and single-cell microorganisms (archaea), but we just don’t know.”

The team worked with Porites lutea coral samples retrieved from a reef near Orpheus Island, north of Townsville, Australia. In the lab, they separated the coral itself from its algal symbiotes and associated microbes — then they did genetic sequencing for all the organisms.

After they had a complete picture of the genetic material involved, they used an algorithm to see which genes each actor in the collaboration could draw from.

“This allows us to answer questions like, ‘What nutrients does the coral need, but not make itself?’,” says Dr. Robbins.

Credit: University of Queensland
Associate Professor David Bourne from JCU and the Australian Institute of Marine Science said having high-quality genomes for a coral and its microbial partners was hugely important.

The study’s findings are important as it is the first overall look at the genetic material of corals, their associated organisms, and of the genes that keep them functioning. Associate Professor David Bourne from James Cook University and the Australian Institute of Marine Science calls the findings “truly ground-breaking”, as, in effect, they represent the “blueprint for coral and their symbiotic communities.”

The team hopes that their findings will be put to good use in safeguarding the world’s coral reefs. These beautiful communities have been created by corals over millions of years, but virtually all have experienced bleaching events in recent years as a consequence of man-made climate warming.

“Our coral reefs support incredible diversity and when we lose reefs, we lose far more than corals. There are many threats to coral, but climate change is the most existential [one] for our reefs,” Dr. Robbins said.

“In 2016 and 2017, nearly 50 percent of all corals on the Great Barrier Reef died, and we don’t see this trajectory reversing if carbon emissions remain at current levels.”

On the one hand, research such as this will enable us to better understand corals and to figure out ways of making them more resilient. On the other hand, however, we shouldn’t rest on our laurels. The most straightforward way to safeguard corals and all other life on Earth is to limit our environmental impact by slashing pollution, emissions, and habitat destruction — even kids know this.

The paper “A genomic view of the reef-building coral Porites lutea and its microbial symbionts” has been published in the journal Nature Microbiology.

Scientists extract the oldest DNA data from 1.7-million-year-old rhino tooth

A group of researchers extracted genetic information from a 1.77 million-year-old rhino tooth—the largest genetic data set this old to ever be confidently recorded. They identified an almost complete set of proteins, a proteome, in the dental enamel of the now-extinct rhino.

Credit: Wikipedia Commons

The findings mark a breakthrough in the field of ancient molecular studies and could solve some of the biggest mysteries of ancient animal and human biology by allowing scientists to accurately reconstruct evolution from further back in time than ever before.

The genetic information discovered is one million years older than the oldest DNA sequenced, which came from a 700,000-year-old horse. The findings by scientists from the University of Copenhagen and St John’s College, University of Cambridge, are published in the journal Nature.

“For 20 years, ancient DNA has been used to address questions about the evolution of extinct species, adaptation, and human migration but it has limitations,” said first author Professor Enrico Cappellini. “Now, for the first time, we have retrieved ancient genetic information which allows us to reconstruct molecular evolution way beyond the usual time limit of DNA preservation.”

Human evolution that is tracked by DNA only covers the last 400,000 years. But the lineages that led to modern humans and to the chimpanzee branched apart around six to seven million years ago. This means scientists currently have no genetic information for more than 90% of the evolutionary path that led to modern humans.

Researchers also do not know what the genetic links are between us and extinct species such as Homo erectus – the oldest known species of human to have had modern human-like body proportions. As things stand, everything that is known is based almost exclusively on anatomical and not genetic information.

In this new study, the team used ancient protein sequencing – based on groundbreaking technology called mass spectrometry – to retrieve genetic information from the tooth. They took samples of dental enamel from the ancient fossil, which was discovered in Dmanisi, Georgia.

Mass spectrometry was used to sequence the ancient protein and retrieved genetic information previously unobtainable using DNA testing. Tooth enamel is the hardest material present in mammals, and the set of proteins it contains lasts longer than DNA and is more genetically informative than collagen, scientists said.

“This research is a game-changer that opens up a lot of options for further evolutionary study in terms of humans as well as mammals. It will revolutionize the methods of investigating evolution based on molecular markers and it will open a completely new field of ancient biomolecular studies, said professor Eske Willerslev.