Skip to main content

Genes to cope with Infections

The bacteria that write new genes to cope with infections



Amid the unprecedented challenges presented by the COVID-19 pandemic, a once obscure enzyme found itself in the spotlight: reverse transcriptase. As laboratories worldwide rushed to develop reliable diagnostic tests, techniques using the enzyme became the gold standard to detect the SARS-2 virus, and a cornerstone of molecular diagnostics. This remarkable enzyme didn’t only facilitate rapid and accurate testing; along with another powerful approach — genome-sequencing — it also helped track the virus’s spread, paving the way for surveillance, better public healthcare, and vaccine development.

The discovery of reverse transcriptase is a story unto itself. Researchers in the labs of Howard Temin and David Baltimore independently discovered it and published their findings in back-to-back articles in the journal Nature in 1970. In his paper, Dr. Baltimore suggested that in the vesicular stomatitis virus, a protein called RNA polymerase was involved in reverse-translating RNA to DNA.

A molecular biology revolution

The discovery was transformative. The prevailing belief at the time was that in all living beings, hereditary information flowed only from DNA to RNA and from RNA to protein (a.k.a. the ‘Central Dogma’). The discoveries of Drs. Temin and Baltimore et al. showed information could flow the other way, too, with RNA giving ‘rise’ to DNA. The name “reverse transcriptase” was however coined by the editor of Nature, in an article discussing the significant advance in an accompanying column.

The discovery’s impact was also immediate. The ability of cells to create DNA copies from RNA revolutionised research methods in molecular biology, where researchers could reverse-transcribe messenger RNAs to pieces of DNA, clone that DNA into bacterial vectors, and study the function of the corresponding genes. In diagnostics, clinicians used reverse transcriptase to convert RNA to DNA and thus estimate the amount of viral material in a given sample. This technique quickly found wide application and use in the study of RNA viruses, including hepatitis B and the human immunodeficiency virus (HIV).

Indeed, the discovery of reverse transcriptase had a significant effect on the management and treatment of HIV infections, including Acquired Immunodeficiency Syndrome (AIDS), in the 1980s. A generation of antiviral agents that specifically targeted the reverse transcriptase enzyme helped convert an otherwise deadly disease to one that could be managed, translating to improving the long-term outcomes and survival of people living with AIDS.

Subsequent studies of the reverse transcriptase enzyme since the 1970s led to mechanistic insights into how viruses use this enzyme to replicate, as well.

Retroelements in the human genome

Reverse transcriptases also had a significant role in shaping the human genome.

The human genome is interspersed in many places with sequences, called elements, that appear to have originated from retroviruses. Thus researchers call them retroelements. Evolutionary biologists believe these retroelements to have been transferred horizontally during the course of millions of years of evolution. (Horizontal gene transfer refers to genes ‘jumping’ between organisms rather than from parent to offspring.) And until recently, researchers also considered them to be “junk” elements: they were repeated through the genome and they seemingly did not confer any function to the human organism.

However, recent evidence has suggested that these retroelements could really have had a profound impact on human biology and evolution, and that they play important roles in a variety of physiological processes.

In a recent paper in the journal Nature Communications, researchers extensively studied the expression of genes in different parts of the human brain from post-mortem brain samples. They reported that the expression of more than a thousand human endogenous retroviruses — a major class of retroelements in the human genome — could be associated with a risk of neuropsychiatric diseases in humans.

Retroelements in the human genome and bacterial reverse transcriptases have a common evolutionary history as well as share functional mechanisms. Bacterial reverse transcriptases — believed to be the precursors of their eukaryotic counterparts — exhibit analogous mechanisms.

The discovery of reverse transcriptase activity across the different domains of life underscores the enzyme’s fundamental role in both prokaryotic and eukaryotic systems as well as a remarkable evolutionary continuity and functional versatility.

Writing genes using reverse transcriptase

Researchers widely believed that bacterial reverse transcriptases were the precursors of their eukaryotic counterparts. They discovered the first reverse transcriptase in bacteria in 1989, with papers published back to back in the journals Science and Cell. In bacteria, as in the case of humans, retroelements are categorised as belonging to three broad groups: the Group II introns, the retrons, and the diversity generating retroelements.

In a preprint paper uploaded to the bioRxiv preprint server on May 8, researchers at Columbia University in New York, led by Stephen Tang and Samuel Sternberg, suggested that when the bacteria Klebsiella pneumoniae is infected by bacteriophages — viruses that infect bacteria — they use a non-coding RNA with specific motifs (or structures) that could bind to reverse transcriptase and instruct cells to create DNA. This DNA copy has multiple copies of a gene that can create a specific protein.

The researchers dubbed this protein ‘Neo’ for “never-ending open-reading frame”. It could place the bacterial cell in a state of suspended animation, blocking its replication, and thus stalling the replication of the invading bacteriophage as well. Thus, the infection is stopped in its tracks.

Recent discoveries — including the role of reverse transcriptase in bacterial defence against bacteriophages — hint at the potential of innovative applications in biotechnology and medicine, especially in the context of emerging antimicrobial resistance, the ability of disease-causing microbes to resist the effects of substances designed to incapacitate or kill them. Further exploring reverse transcriptases could also reveal novel mechanisms of genetic evolution and viral resistance, potentially leading to new therapeutic strategies and biotechnological tools.

International Conference on Genetics and Genomics of Diseases 




For Enquiries: genetics@healthcarek.com 

Get Connected Here 
--------------------------------- 
--------------------------------- 
facebook.com/profile.php?id=61555903296992 
tumblr.com/blog/dorita0211 

Comments

Post a Comment

Popular posts from this blog

Genetics role in ovarian cancer

The Medical Minute: Genetics play big role in ovarian cancer In 2024, about 19,680 women in the United States will receive a new diagnosis of ovarian cancer and 12,740 women will die from the disease, said Dr. Shaina Bruce , a gynecologic oncologist at Penn State Cancer Institute . The median age of all patients who develop ovarian cancer is 63. Historically, women at increased risk for ovarian cancer are recommended to have their fallopian tubes and ovaries removed when they have completed having children. Taking that step to protect themselves comes at a heavy price ― surgical menopause. But Bruce said medical science is catching up with ovarian cancer. Studies could lead to new methods for preventative care and the surgery needed to lower risk may be easier than it once was. Below, during Gynecologic Cancer Awareness Month, Bruce discusses the disease and why acting to reduce your risk is worth it. What’s the connection between heredity and ovarian cancer? About 25% of all cases of ...
Post a Comment
Read more

Multifactorial Genetic Conditions

Multifactorial Genetic Conditions Multifactorial genetic conditions are disorders caused by the combined effects of multiple genes and environmental factors , rather than a single gene mutation . These conditions do not follow classic Mendelian inheritance patterns and instead result from complex gene–environment interactions . Factors such as lifestyle, nutrition, infections, stress, and exposure to toxins can significantly influence disease onset and severity in genetically susceptible individuals. Common examples include diabetes, cardiovascular diseases , neural tube defects, asthma, and many neuropsychiatric disorders. Understanding multifactorial inheritance is essential for risk prediction, preventive medicine, and personalized healthcare strategies. Multifactorial inheritance, polygenic traits, gene–environment interaction, complex diseases, genetic susceptibility, environmental risk factors, non-Mendelian inheritance, disease predisposition, polygenic risk score, precision ...
Post a Comment
Read more

X chromosome

Gene on the X chromosome may help explain high multiple sclerosis rates in women Brain inflammation may be fueled by a gene on the X chromosome, a new study in mice suggests. And in female mice, who carry two X chromosomes, a diabetes drug called metformin may work to counteract that inflammation. If these findings bear out in later studies, they could help to unravel the long-standing mystery of why women, who have two copies of this inflammation-driving gene, are more prone to certain autoimmune diseases, particularly after menopause. A disparity between the sexes Our bodies are patrolled by immune cells that provide protection against bacteria and viruses, but sometimes, these defenses turn on us. In the autoimmune disorder multiple sclerosis (MS), for instance, the immune system attacks myelin, the fatty insulation surrounding the nerve fibers in the brain and spinal cord. This leads to symptoms such as muscle weakness and difficulty walking, as well issues with memory and thinking...
Post a Comment
Read more