Lifeboat Foundation: Safeguarding Humanity
Toggle light / dark theme

Blog

Category: evolution – Page 4

Analysis of genomic heterogeneity and the mutational landscape in cutaneous squamous cell carcinoma through multi-patient-targeted single-cell DNA sequencing

Cutaneous squamous cell carcinoma (CSCC) is a prevalent skin cancer with aggressive progression that poses significant challenges, especially in metastatic cases. Single-cell DNA sequencing (scDNA-seq) has become an advanced technology for elucidating tumor heterogeneity and clonal evolution. However, comprehensive scDNA-seq studies and tailored mutation panels for CSCC are lacking.

We analyzed the genomic landscape of Chinese CSCC patients via a Multi-Patient-Targeted (MPT) scDNA-seq approach. This method combined bulk exome sequencing with Tapestri scDNA-seq. Mutations identified through bulk sequencing were used to design a targeted panel for scDNA-seq. Comparative analysis was conducted to explore the associations between specific gene mutations and clinical characteristics such as tumor stage and patient sex. Clonal evolution analysis was performed to understand the evolutionary trajectories of the tumors.

Bulk sequencing revealed a diverse spectrum of somatic mutations in CSCC tumors, with missense mutations being predominant. The top tumor mutations, such as those in NOTCH1, TP53, NOTCH2, TTN, MUC16, RYR2, PRUNE2, DMD, HRAS, and CDKN2A, presented similar frequencies to those reported in studies in Korean and Caucasian populations. However, the mutation frequencies of HRAS, TTN, MUC16 and MUC4 were significantly different from the Korean and Caucasian populations. Comparative analysis revealed associations between specific gene mutations and clinical characteristics such as tumor stage and patient sex. Clonal evolution analysis via scDNA-seq revealed distinct evolutionary trajectories and their potential correlation with tumor development and patient prognosis. Furthermore, scDNA-seq identified two low-frequency mutation clones, NLRP5 and HMMR, which play important roles in the clonal evolution of CSCC.

P53 in the DNA-Damage-Repair Process

The cells in the human body are continuously challenged by a variety of genotoxic attacks. Erroneous repair of the DNA can lead to mutations and chromosomal aberrations that can alter the functions of tumor suppressor genes or oncogenes, thus causing cancer development. As a central tumor suppressor, p53 guards the genome by orchestrating a variety of DNA-damage-response (DDR) mechanisms. Already early in metazoan evolution, p53 started controlling the apoptotic demise of genomically compromised cells. p53 plays a prominent role as a facilitator of DNA repair by halting the cell cycle to allow time for the repair machineries to restore genome stability. In addition, p53 took on diverse roles to also directly impact the activity of various DNA-repair systems. It thus appears as if p53 is multitasking in providing protection from cancer development by maintaining genome stability.

A cGAS-mediated mechanism in naked mole-rats potentiates DNA repair and delays aging

Efficient DNA repair might make possible the longevity of naked mole-rats. However, whether they have distinctive mechanisms to optimize functions of DNA repair suppressors is unclear. We find that naked mole-rat cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS) lacks the suppressive function of human or mouse homologs in homologous recombination repair through the alteration of four amino acids during evolution. The changes enable cGAS to retain chromatin longer upon DNA damage by weakening TRIM41-mediated ubiquitination and interaction with the segregase P97. Prolonged chromatin binding of cGAS enhanced the interaction between repair factors FANCI and RAD50 to facilitate RAD50 recruitment to damage sites, thereby potentiating homologous recombination repair.

300,000-year-old genomes: History of the Schöningen horses deciphered

For the first time, a research team from the Senckenberg Center for Human Evolution and Paleoenvironment at the University of Tübingen and the Schöningen Research Center have reconstructed the genomes of an extinct horse species, Equus mosbachensis, from the archaeological site of Schöningen in Lower Saxony, which is approximately 300,000 years old.

Thanks to exceptionally favorable preservation conditions, the researchers were able to identify the oldest DNA yet discovered from an open-air site. Their analyses show that the Schöningen horses belong to a lineage that is considered to be the origin of all modern horses. The study is published in the journal Nature Ecology & Evolution.

Domestic and , donkeys and zebras all belong to the sole genus of the family Equidae still in existence today. But a look into the shows that more than 35 different genera and hundreds of now extinct equine species occurred throughout the past.

Long-term radio observations track the evolution of a tidal disruption event

Astronomers from Curtin University in Australia and elsewhere have performed radio observations of a tidal disruption event known as AT2019azh. Results of the new study, published September 22 on the arXiv preprint server, provide crucial information regarding the evolution of this event.

Tidal events (TDEs) are phenomena that occur when a star passes close enough to a (SMBH) and is destroyed by the black hole’s tidal forces. As a result, around half of the stellar debris is unbound from the system, while the rest of the material remains bound, producing a luminous flare as it accretes onto the SMBH.

AT2019azh is a TDE at a redshift of 0.022, detected in 2019 in the galaxy KUG 0180+227. It showcases persistent blue colors, has a high blackbody temperature, and previous observations have reported a lack of spectroscopic features associated with a supernova or an (AGN), which confirmed its TDE nature.

Human genome rearrangement with programmable bridge recombinases

Bridge recombinases were discovered from parasitic mobile genetic elements that hijack bacterial genomes for their own survival. Presented last year in the journal Nature, the same team found these elements encode both a new class of structured guide RNA, which they named a “bridge RNA”, and a recombinase enzyme that rearranges DNA. The researchers repurposed this natural system by reprogramming the bridge RNA to target new DNA sequences, creating the foundation for a new type of precise gene editing tool they called bridge recombinases.

Starting with 72 different natural bridge recombinase systems isolated from bacteria, the team found that about 25% showed some activity in human cells, but most were barely detectable. Only one system, called ISCro4, showed enough measurable activity to enable further optimization. They then systematically improved both the protein and its RNA guide components, testing thousands of variations until they achieved 20% efficiency for DNA insertions and 82% specificity for hitting intended targets in the human genome.

While CRISPR uses a single guide RNA to target one DNA location, bridge RNAs are unique because they can simultaneously recognize two different DNA targets through distinct binding loops. This dual recognition enables the system to perform coordinated rearrangements such as bringing together distant chromosomal regions to excise genetic material or flipping existing sequences in reverse orientation. The system acts as molecular scaffolding that holds two DNA sites together while the recombinase enzyme performs the rearrangement reaction.

As a proof-of-concept, the researchers created artificial DNA constructs containing the same toxic repeat sequences that cause progressive neuromuscular decline in Friedreich’s ataxia patients. While healthy individuals carry fewer than 10 sequential copies of a three-letter DNA sequence, people with the disorder can harbor up to 1,700 copies, which interferes with normal gene function. The engineered ISCro4 successfully removed these repeats from the artificial constructs, in some cases eliminating over 80% of the expanded sequences.

The team also demonstrated that bridge recombinases could replicate existing therapeutic approaches by successfully removing the BCL11A enhancer, the same target disrupted in an FDA-approved sickle cell anemia treatment. And because bridge recombinases can move massive amounts of DNA, the technology could also help model the large-scale genomic rearrangements associated with cancers.

For decades, gene-editing science has been limited to making small, precise edits to human DNA, akin to correcting typos in the genetic code. The researchers are changing that paradigm with a universal gene editing system that allows for cutting and pasting of entire genomic paragraphs, rearranging whole chapters, and even restructuring entire passages of the genomic manuscript.

Continue reading “Human genome rearrangement with programmable bridge recombinases” | >

Shining a light on dark valleytronics: First direct observation of dark excitons in atomically thin materials

In a world-first, researchers from the Femtosecond Spectroscopy Unit at the Okinawa Institute of Science and Technology (OIST) have directly observed the evolution of the elusive dark excitons in atomically thin materials, laying the foundation for new breakthroughs in both classical and quantum information technologies.

Their findings have been published in Nature Communications.

Professor Keshav Dani, head of the unit, says, Dark excitons have great potential as information carriers, because they are inherently less likely to interact with light, and hence less prone to degradation of their quantum properties. However, this invisibility also makes them very challenging to study and manipulate.

Autism’s High Prevalence Could Be an Evolutionary Trade-Off

Autism-linked genes evolved rapidly in humans. They may have aided brain growth and language. A recent study published in Molecular Biology and Evolution by Oxford University Press suggests that the relatively high prevalence of Autism Spectrum Disorders in humans may be rooted in evolutionary hi

/* */