Lifeboat Foundation

A University of Bristol-led study found that life on Earth, stemming from a common ancestor called LUCA, flourished soon after the planet’s formation.

Through genetic analysis and evolutionary modeling, researchers pinpointed LUCA’s existence to about 4.2 billion years ago, revealing it as a complex organism with an early immune system integral to Earth’s earliest ecosystems.

Luca’s genetic blueprint and its descendants.

This is pretty impressive, they can move around individual cells. Video in comments:

Researchers at the HUN-REN Biological Research Centre, Szeged, have developed tiny tools to capture individual cells. According to their study published in the journal Advanced Materials, key innovations of using flexible microrobots is that they do not require any treatment of the cells to grab them and also allow the cells to be released after examination, enabling more efficient investigations than ever before.

Continue reading “HUN-REN BRC researchers develop laser-guided microrobots for cell-capturing” »

In new research, Arizona State University scientists and their colleagues investigated genetic changes occurring in a naturally isolated population of the water flea, Daphnia pulex. This tiny crustacean, barely visible to the naked eye, plays a crucial role in freshwater ecosystems and offers a unique window into natural selection and evolution.

A long-term study since 1929 has revealed significant insights into barley’s evolution, showing its adaptation to different environments and the substantial impact of natural selection. This research underscores the limitations of evolutionary breeding and highlights the need for further exploration to enhance crop yields.

Utilizing one of the world’s oldest biological experiments, which commenced in 1929, researchers have revealed how barley, a major crop, has been influenced by agricultural pressures and its evolving natural environment. These findings highlight the significance of long-term studies in comprehending the dynamics of adaptive evolution.

The survival of cultivated plants after their dispersal across different environments is a classic example of rapid adaptive evolution. For example, barley, an important neolithic crop, spread widely after domestication over 10,000 years ago to become a staple source of nutrition for humans and livestock throughout Europe, Asia, and Northern Africa over just a few thousand generations. Such rapid expansion and cultivation have subjected the plant to strong selective pressures, including artificial selection for desired traits and natural selection by being forced to adapt to diverse new environments.

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LA JOLLA (March 4, 2024)—Charles Darwin described evolution as “descent with modification.” Genetic information in the form of DNA sequences is copied and passed down from one generation to the next. But this process must also be somewhat flexible, allowing slight variations of genes to arise over time and introduce new traits into the population.

But how did all of this begin? In the origins of life, long before cells and proteins and DNA, could a similar sort of evolution have taken place on a simpler scale? Scientists in the 1960s, including Salk Fellow Leslie Orgel, proposed that life began with the “RNA World,” a hypothetical era in which small, stringy RNA molecules ruled the early Earth and established the dynamics of Darwinian evolution.

New research at the Salk Institute now provides fresh insights on the origins of life, presenting compelling evidence supporting the RNA World hypothesis. The study, published in Proceedings of the National Academy of Sciences (PNAS) on March 4, 2024, unveils an RNA enzyme that can make accurate copies of other functional RNA strands, while also allowing new variants of the molecule to emerge over time. These remarkable capabilities suggest the earliest forms of evolution may have occurred on a molecular scale in RNA.

Life’s evolutionary timescale is typically calibrated to the oldest fossil occurrences. However, the veracity of fossil discoveries from the early Archaean period has been contested^11,12. Relaxed Bayesian node-calibrated molecular clock approaches provide a means of integrating the sparse fossil and geochemical record of early life with the information provided by molecular data; however, constraining LUCA’s age is challenging due to limited prokaryote fossil calibrations and the uncertainty in their placement on the phylogeny. Molecular clock estimates of LUCA^13,14,15 have relied on conserved universal single-copy marker genes within phylogenies for which LUCA represented the root. Dating the root of a tree is difficult because errors propagate from the tips to the root of the dated phylogeny and information is not available to estimate the rate of evolution for the branch incident on the root node. Therefore, we analysed genes that duplicated before LUCA with two (or more) copies in LUCA’s genome¹⁶. The root in these gene trees represents this duplication preceding LUCA, whereas LUCA is represented by two descendant nodes. Use of these universal paralogues also has the advantage that the same calibrations can be applied at least twice. After duplication, the same species divergences are represented on both sides of the gene tree^17,18 and thus can be assumed to have the same age. This considerably reduces the uncertainty when genetic distance (branch length) is resolved into absolute time and rate. When a shared node is assigned a fossil calibration, such cross-bracing also serves to double the number of calibrations on the phylogeny, improving divergence time estimates. We calibrated our molecular clock analyses using 13 calibrations (see ‘Fossil calibrations’ in Supplementary Information). The calibration on the root of the tree of life is of particular importance. Some previous studies have placed a younger maximum constraint on the age of LUCA based on the assumption that life could not have survived Late Heavy Bombardment (LHB) (~3.7–3.9 billion years ago (Ga))¹⁹. However, the LHB hypothesis is extrapolated and scaled from the Moon’s impact record, the interpretation of which has been questioned in terms of the intensity, duration and even the veracity of an LHB episode^20,21,22,23. Thus, the LHB hypothesis should not be considered a credible maximum constraint on the age of LUCA. We used soft-uniform bounds, with the maximum-age bound based on the time of the Moon-forming impact (4,510 million years ago (Ma) ± 10 Myr), which would have effectively sterilized Earth’s precursors, Tellus and Theia¹³. Our minimum bound on the age of LUCA is based on low δ⁹⁸ Mo isotope values indicative of Mn oxidation compatible with oxygenic photosynthesis and, therefore, total-group Oxyphotobacteria in the Mozaan Group, Pongola Supergroup, South Africa^24,25, dated minimally to 2,954 Ma ± 9 Myr (ref. ²⁶).

Our estimates for the age of LUCA are inferred with a concatenated and a partitioned dataset, both consisting of five pre-LUCA paralogues: catalytic and non-catalytic subunits from ATP synthases, elongation factor Tu and G, signal recognition protein and signal recognition particle receptor, tyrosyl-tRNA and tryptophanyl-tRNA synthetases, and leucyl-and valyl-tRNA synthetases²⁷. Marginal densities (commonly referred to as effective priors) fall within calibration densities (that is, user-specified priors) when topologically adjacent calibrations do not overlap temporally, but may differ when they overlap, to ensure the relative age relationships between ancestor-descendant nodes. We consider the marginal densities a reasonable interpretation of the calibration evidence given the phylogeny; we are not attempting to test the hypothesis that the fossil record is an accurate temporal archive of evolutionary history because it is not²⁸.

Increased frailty, higher incidence of diseases, and death. As the population grows older, there is a need to reveal mechanisms associated with aging that could spearhead treatments to postpone the onset of age-associated decline, extend both healthspan and lifespan. One possibility is targeting the sirtuin SIRT1, the founding member of the sirtuin family, a highly conserved family of histone deacetylases that have been linked to metabolism, stress response, protein synthesis, genomic instability, neurodegeneration, DNA damage repair, and inflammation. Importantly, sirtuins have also been implicated to promote health and lifespan extension, while their dysregulation has been linked to cancer, neurological processes, and heart disorders. SIRT1 is one of seven members of sirtuin family; each requiring nicotinamide adenine dinucleotide (NAD⁺) as co-substrate for their catalytic activity. Overexpression of yeast, worm, fly, and mice SIRT1 homologs extend lifespan in each animal, respectively. Moreover, lifespan extension due to calorie restriction are associated with increased sirtuin activity. These findings led to the search for a calorie restriction mimetic, which revealed the compound resveratrol; (3, 5, 4′-trihydroxy-trans-stilbene) belonging to the stilbenoids group of polyphenols. Following this finding, resveratrol and other sirtuin-activating compounds have been extensively studied for their ability to affect health and lifespan in a variety of species, including humans via clinical studies.

Aging is associated with a progressive metabolic, physiological decline and can be genetically and environmentally modified (Helfand and Rogina, 2000). The search for the molecular basis of aging led to the identification of several pathways associated with longevity including insulin/IGF-1, target of rapamycin (TOR) and the Sirtuins (Kenyon, 2010; Chen et al., 2022). The sirtuins are a family of nicotinamide adenine dinucleotide (NAD⁺)-dependent histone deacetylases (Haigis and Sinclair, 2010; Hall et al., 2013; Bonkowski and Sinclair, 2016; Dai et al., 2018; Singh et al., 2018). Sirtuins are also categorized as deacetylases because they catalyze the post-translational modification of signaling molecules including decrotonylation, ADP-ribosylation, diacylation, desuccinylation, demalonylation, depropynylation, delipoamidation, and deglutarylation, and other long-chain fatty acid deacylations (Feldman, Baeza, and Denu, 2013; Choudhary et al., 2014; Fiorentino et al., 2022).

In mammals, there are seven members (SIRT1-SIRT7) including SIRT1, SIRT6 and SIRT7, which are localized to the nucleus, and SIRT3, SIRT4, and SIRT5 localized to the mitochondria, SIRT2 localized to the cytosol, and SIRT1 also localized to cytosol in some cell types (Bonkowski and Sinclair, 2016). As histone deacetylases, sirtuins function by removing acetyl groups from the target proteins resulting in either inhibition or activation. SIRT1, SIRT6 and SIRT7 have many functions including: regulators of transcription, control of cellular metabolism, DNA repair, cell survival, tissue regeneration, inflammation, circadian rhythms and neuronal signaling (Haigis and Sinclair, 2010). SIRT3-5 are important for switching to mitochondrial oxidative metabolism during CR and modulate stress tolerance (Verdin et al., 2010).

The genetically modified lymphocytes were then multiplied into the hundreds of millions in the laboratory and infused back into the patients, where they expressed the tumor-specific T-cell receptors and continued to multiply.

“By taking the natural T-cell receptors that are present in a very small number of cells and putting them into normal lymphocytes for which we have enormous numbers—a million in every thimbleful of blood—we can generate as many cancer-fighting cells as we want,” Dr. Rosenberg explained.

As part of a larger phase 2 trial, seven patients with metastatic colon cancer were treated with the experimental personalized cellular immunotherapy. All seven received several doses of the immunotherapy drug pembrolizumab (Keytruda) before the cell therapy and another immunotherapy drug called IL-2 afterward. Three patients had substantial shrinkage of metastatic tumors in the liver, lung, and lymph nodes that lasted for four to seven months. The median time to disease progression was 4.6 months.