Evo 2, the largest AI model in biology to date, can accurately predict the effects of all types of genetic mutations
Category: genetics – Page 20
Strategic gene placement in bacteria offers insights into evolutionary success
Bioinformaticians from Heinrich Heine University Düsseldorf (HHU) and the university in Linköping (Sweden) have established that the genes in bacterial genomes are arranged in a meaningful order. In the journal Science, they explain that the genes are arranged by function: If they become increasingly important for faster growth, they are located near the origin of DNA replication. Accordingly, their position influences how their activity changes with the growth rate.
Are genes distributed randomly along the bacterial chromosome, as if scattered from a salt shaker? This opinion, which is held by a majority of researchers, has now been disputed by a team of bioinformaticians led by Professor Dr. Martin Lercher, head of the research group for Computational Cell Biology at HHU.
When bacteria replicate their genetic material in preparation for cell division, the process starts at a specific point on the bacterial chromosome and continues along the chromosome in both directions.
Cell biologists discover two proteins are key to proper transfer of genetic material
The biological research of UC Santa Cruz’s Needhi Bhalla to determine the molecular motions at the heart of heredity has yielded a new discovery: The proper transfer of genetic materials depends on two key proteins that choreograph the delicate dance between chromosomes when sexual-reproduction cells divide.
When cells split to create eggs and sperm, they must undergo a crucial process called “meiotic crossover recombination.” This mechanism ensures that genetic material is properly shuffled between chromosomes, preventing errors that could lead to disorders such as miscarriages, infertility, birth defects, and even cancer.
This process also results in the endearing transfer of traits that parents see in their children. And beyond contributing to parental pride, Bhalla says meiotic crossover recombination is fundamental for human evolution by promoting genetic diversity. That’s why the identification of two specific proteins that play central roles in controlling how and where these crossovers happen is so significant.
Which Biomarkers Are Associated With Cancer Cachexia?
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Cancer cells mimic Sherpa genes to survive low oxygen
Results of a study show convergent genetic adaptation under hypoxia (lack of oxygen) between populations living at high-altitude in the Himalayan region such as Tibetans and Sherpas, and the development of oxygen-starved cancer cells. The study was directed by Rodrigo Toledo, Head of the Vall d’Hebron Institute of Oncology’s (VHIO) Biomarkers and Clonal Dynamics Group and published in the journal Cancer Discovery.
Patients with cyanotic congenital heart disease (CCHD) are chronically hypoxic and have an estimated six-fold higher risk of developing pheochromocytoma and paraganglioma (PPGL), which are associated with neuroendocrine tumors (NETs) of the adrenal glands and/or paraganglia, respectively. These cancers can continue to grow and proliferate under chronic hypoxia.
“With this study, we aimed to achieve deeper insights into how tumors can survive, grow, and even metastasize under low oxygen conditions, known as hypoxia. Our findings reveal a broad convergence in genetic adaptation in tumors that continue to develop and grow under hypoxia, and in high-altitude populations who thrive in such a challenging environment,” said Toledo, corresponding author of this present article.
Smart delivery tech boosts CRISPR efficiency, restores vision in mice
A research team from Helmholtz Munich and the Technical University of Munich has developed an advanced delivery system that transports gene-editing tools based on the CRISPR/Cas9 gene-editing system into living cells with significantly greater efficiency than before. Their technology, ENVLPE, uses engineered non-infectious virus-like particles to precisely correct defective genes—demonstrated successfully in living mouse models that are blind due to a mutation.
This system also holds promise for advancing cancer therapy by enabling precise genetic manipulation of engineered immune cells, making them more universally compatible and thus more accessible for a larger group of cancer patients.
The work is published in the journal Cell.
Scientists discover that fruit fly larvae can sense electric fields
While it may be an unfamiliar sensation to humans, electroreception is relatively commonplace in the animal kingdom. Sharks, bees and even the platypus all share this ability to detect electric fields in their environment.
Scientists at UC Santa Barbara have just added fruit flies to that list. A team of researchers led by Matthieu Louis found that fruit fly larvae can sense electric fields and navigate toward the negative electric potential using a small set of sensory neurons in their head.
The findings, published in Current Biology, present an immense opportunity. Fruit flies are arguably the most commonly used experimental animals, the basis for studies in fields as disparate as genetics, neurobiology and aging. Uncovering electroreception in fruit flies opens new avenues of research into the basis of this sense and could even lead to new techniques in bioengineering.
A geological timescale for bacterial evolution and oxygen adaptation
Microbial life has dominated Earth’s history but left a sparse fossil record, greatly hindering our understanding of evolution in deep time. However, bacterial metabolism has left signatures in the geochemical record, most conspicuously the Great Oxidation Event (GOE). We combine machine learning and phylogenetic reconciliation to infer ancestral bacterial transitions to aerobic lifestyles, linking them to the GOE to calibrate the bacterial time tree. Extant bacterial phyla trace their diversity to the Archaean and Proterozoic, and bacterial families prior to the Phanerozoic. We infer that most bacterial phyla were ancestrally anaerobic and adopted aerobic lifestyles after the GOE. However, in the cyanobacterial ancestor, aerobic metabolism likely predated the GOE, which may have facilitated the evolution of oxygenic photosynthesis.
Cellular regulator of mRNA vaccine revealed!
First, the team discovered that heparan sulfate (HSPG), a sulfated glycoprotein on the cell surface, plays a crucial role in attracting LNPs and facilitating mRNA entry into the cell.
- Second, they identified V-ATPase, a proton pump at the endosome, which acidifies the vesicle and causes LNPs to become positively charged, enabling them to temporarily disrupt the endosomal membrane and release the mRNA into the cytoplasm to be expressed.
- Lastly, the study uncovered the role of TRIM25, a protein involved in the cellular defense mechanism. TRIM25 binds to and induces the rapid degradation of exogenous mRNAs, preventing their function.
So how do the mRNA vaccines evade this cellular defense? A key finding of the study was that mRNA molecules containing a special modification called N1-methylpseudouridine (m1Ψ)—which was awarded the 2023 Nobel Prize in Physiology or Medicine—can evade TRIM25 detection. This modification prevents TRIM25 from binding to mRNA, enhancing the stability and effectiveness of mRNA vaccines. This discovery not only explains how mRNA vaccines evade cellular surveillance mechanisms but also emphasizes the importance of this modification in enhancing the therapeutic potential of mRNA-based treatments.
Additionally, the research highlighted the critical role of proton ions in this process. When the LNPs rupture the endosomal membrane, proton ions are released into the cytoplasm, which activates TRIM25. These proton ions act as a signal that alerts the cell to the invading foreign RNA, which in turn triggers a defense response. This is the first study to demonstrate that proton ions serve as immune signaling molecules, providing new insights into how cells protect themselves from foreign RNA.
A team of researchers has uncovered a key cellular mechanism that affects the function of mRNA vaccines and therapeutics. Their study, recently published in Science, provides the first comprehensive understanding of how mRNA vaccines are delivered, processed, and degraded within cells—a breakthrough that could pave the way for more effective vaccines and RNA-based treatments.