Proceedings of the National Academy of Sciences of the United States of America最新文献

The Asteraceae (Compositae) is the largest flowering plant family, ubiquitous in most terrestrial communities, and morphologically diverse. A two-step, ancient whole genome triplication (paleohexaploidization) occurred at approximately the same time as the evolutionary innovation and adaptive radiation of the family during the middle Eocene. Despite its importance, the consequences of this triplication have yet to be tracked in context of the Asteraceae genome evolution. To do so, we applied a synteny oriented phylogenomic analysis of 23 Asterales genomes. We identified 16 genomic groups that date back to the common diploid ancestor of all Asteraceae. Each group underwent triplication, resulting in 48 genomic blocks (16 × 3) that collectively represent the ancestral Asteraceae genome, excluding the early-diverging lineages which do not share the second step. We then analyzed the evolutionary dynamics of the 48 genomic blocks across the Asteraceae phylogeny. We found that modern Asteraceae genomes are genetic mosaics of three progenitor genomes, shaped by genomic exchanges, chromosomal rearrangements, and gene fractionation. One hundred fifty-seven genes retained three paleohexaploid-derived syntenic paralogs across most Asteraceae species. Transcription factors and auxin-related genes are significantly overrepresented in these triplets, and expression of the paleohexaploidy paralogs is spatiotemporally differentiated. These genes are involved in the development of floral capitula, a remarkable morphological innovation of the family. The discovery of the 157 triplicated genes can direct further study to understand the evolutionary innovation, and the synteny-phylogenomic framework provides a comparative framework to characterize newly sequenced Asteraceae genomes.

How thousands of microtubules (MTs) and molecular motors self-organize into spindles remains poorly understood. By combining static, nanometer-resolution, large-scale electron tomography reconstructions and dynamic, optical-resolution, polarized light microscopy, we test an active liquid crystal continuum theory of mitotic spindles in human tissue culture cells. At micron length scales, probed by optical microscopy, the continuum theory accurately captures spindle morphology and fluctuation spectra, indicating that local interactions-polymerization, alignment, diffusion, and polar transport-govern the collective behaviors of MTs in human mitotic spindles. Electron tomography data enables tests of the continuum theory at submicron scales, revealing that chromosome-attached kinetochore microtubules (KMTs) show distinctive lateral organization not explained by the coarse-grained theory, while the non-KMTs that make up the bulk of the spindle follow the theory down to ∼300 nm length scales. At length scales below ∼300 nm, fluctuations arising from the intrinsic discreteness of the microtubule ensemble dominate over the collective correlations predicted from the continuum theory. Taken together, these findings show that an active liquid-crystal theory can quantitatively capture the self-organization of human mitotic spindles on long length scales and provides a means to measure the spindle's material properties, while also pointing to the existence of additional processes contributing to the behaviors of KMTs.

TMEM16A channels conduct Ca²⁺-activated Cl^- currents that underlie essential physiological processes including epithelial secretion, smooth muscle contraction, and sensory transduction. Channel activation requires both intracellular Ca²⁺ and the signaling phospholipid phosphatidylinositol 4,5-bisphosphate (PIP₂), yet the molecular basis of this dual regulation has remained unclear. Using gating molecular-dynamics simulations and structure-guided electrophysiology, we show that PIP₂ and Ca²⁺ cooperatively gate TMEM16A through an allosterically coupled electrostatic network centered on the α4 helix. Specific PIP₂ headgroup phosphate interactions are essential for coupling Ca²⁺ binding to channel opening, while the PIP₂ acyl chains engage hydrophobic surfaces of the helix to stabilize the open conformation. Disrupting either component of this lipid-protein interface reduces apparent PIP₂ affinity and impairs activation, whereas long-chain PIP₂ fully restores wild-type activity. These interactions act in concert with Ca²⁺-dependent structural rearrangements that widen the conduction pathway and enable Cl^- permeation. Our findings establish that both the headgroup phosphates and acyl chains of PIP₂ play indispensable and complementary roles in TMEM16A gating. This mechanism defines a cooperative lipid-ion activation process that provides a general framework for understanding phosphoinositide regulation of ion channels and offers opportunities for structure-based design of TMEM16A modulators.

More than 100 historically, archaeologically and ethnographically attested numerical notations have been used over the past 5,000 y; however, because most of those systems are no longer used, experimental investigation is challenging. Prior research often assumes, rather than demonstrates, the inferiority of notations like Roman numerals. Gradience is a principle whereby the length of numeral phrases correlates with the magnitude of the numbers being represented. In general, but inconsistently, larger numbers require more signs, just as larger sets of abstract dot patterns occupy more space. This study compares the gradience of 13 numerical notations varying in phylogenetic family, linguistic family, and structural properties, using two indices, inversion (how often N + 1 requires fewer signs than N) and jitter (the mean length difference between successive numbers). Place value systems are highly gradient; i.e., their length indexes numerical magnitude more accurately than other systems. The relationship between the structural properties of notations and the two indices of jitter and inversion is complex. Next, a cultural-evolutionary analysis compares the older additive Roman numerals to the eventually predominant subtractive variant (e.g., XIX = 19). Subtractive Roman numerals are more concise and have a lower jitter than additive ones, but at the cost of a significantly higher inversion ratio. This analysis permits the evaluation of cultural-evolutionary hypotheses grounded in the representational properties of attested notations, even when cognitive tests are not feasible. Several avenues for future experimental investigation using attested or constructed notations of varying properties are proposed.