Biology subjects

Tao, Q.

Publications and source records attributed to Tao, Q..

28 records · Page 2Linked to original sources

bioRxiv2021

Ciliary control of meiotic chromosomal pairing mechanics and germ cell morphogenesis

The hallmark of meiosis is chromosomal pairing and synapsis via synaptonemal complexes, but chromosomal pairing also depends on cytoplasmic counterparts that tether and rotate telomeres on the nuclear envelope. Telomeres slide on perinuclear microtubules, shuffling chromosomes and mechanically driving their homology searches. Pull of telomeres towards the centrosome drives formation of the "zygotene chromosomal bouquet". These telomere dynamics are essential for pairing and fertility, and the bouquet, discovered in 1900, is universally conserved. Nevertheless, how cytoplasmic counterparts of bouquet formation are mechanically regulated has remained enigmatic. Here, we report the "zygotene cilium" - a previously unrecognized cilium, in oocytes. We show in zebrafish that this cilium specifically connects to the bouquet centrosome, constituting a cable system of the cytoplasmic bouquet machinery. Furthermore, zygotene cilia extend throughout the germline cyst, a conserved germ cell organization. Using multiple ciliary mutants and laser-induced excision, we demonstrate that the zygotene cilium is essential for chromosomal bouquet and synaptonemal complex formation, germ cell morphogenesis, ovarian development and fertility. Mechanistically, we provide evidence that the cilium functions at least partly via anchoring the bouquet centrosome in order to counterbalance telomere rotation and pulling. We also show that the zygotene cilium is conserved in both male and female meiosis in zebrafish, as well as in mammals. Our work uncovers the novel concept of a cilium as a critical player in meiosis and sheds new light on reproduction phenotypes in ciliopathies. We propose a cellular paradigm that cilia can control chromosomal dynamics.

cell biology↗

bioRxiv2020

An evolutionary portrait of the progenitor SARS-CoV-2 and its dominant offshoots in COVID-19 pandemic

We report the likely most recent common ancestor of SARS-CoV-2 - the coronavirus that causes COVID-19. This progenitor SARS-CoV-2 genome was recovered through a novel application and advancement of computational methods initially developed to reconstruct the mutational history of tumor cells in a patient. The progenitor differs from the earliest coronaviruses sampled in China by three variants, implying that none of the earliest patients represent the index case or gave rise to all the human infections. However, multiple coronavirus infections in China and the USA harbored the progenitor genetic fingerprint in January 2020 and later, suggesting that the progenitor was spreading worldwide as soon as weeks after the first reported cases of COVID-19. Mutations of the progenitor and its offshoots have produced many dominant coronavirus strains, which have spread episodically over time. Fingerprinting based on common mutations reveals that the same coronavirus lineage has dominated North America for most of the pandemic. There have been multiple replacements of predominant coronavirus strains in Europe and Asia and the continued presence of multiple high-frequency strains in Asia and North America. We provide a continually updating dashboard of global evolution and spatiotemporal trends of SARS-CoV-2 spread (http://sars2evo.datamonkey.org/).

evolutionary biology↗

bioRxiv2020

Molecular architecture of the luminal ring of the Xenopus laevis nuclear pore complex

Nuclear pore complex (NPC) mediates the flow of substances between the nucleus and cytoplasm in eukaryotic cells. Here we report the cryo-electron tomography (cryo-ET) structure of the luminal ring (LR) of the NPC from Xenopus laevis oocyte. The observed key structural features of the LR are independently confirmed by single-particle cryo-electron microscopy (cryo-EM) analysis. The LR comprises eight butterfly-shaped subunits, each containing two symmetric wings. Each wing consists of four elongated, tubular protomers. Within the LR subunit, the eight protomers form a Finger domain, which directly contacts the fusion between the inner and outer nuclear membranes, and a Grid domain, which serves as a rigid base for the Finger domain. Two neighbouring LR subunits interact with each other through the lateral edges of their wings to constitute a Bumper domain, which displays two major conformations and appears to cushion neighbouring NPCs. Our study reveals previously unknown features of the LR and potentially explains the elastic property of the NPC.

biophysics↗

bioRxiv2020

Structure of the Cytoplasmic Ring of the Xenopus laevis Nuclear Pore Complex

Nuclear pore complex (NPC) exhibits structural plasticity and has only been characterized at local resolutions of up to 15 [A] for the cytoplasmic ring (CR). Here we present a single-particle cryo-electron microscopy (cryo-EM) structure of the CR from Xenopus laevis NPC at average resolutions of 5.5-7.9 [A], with local resolutions reaching 4.5 [A]. Improved resolutions allow identification and placement of secondary structural elements in the majority of the CR components. The two Y complexes in each CR subunit interact with each other and associate with those from flanking subunits, forming a circular scaffold. Within each CR subunit, the Nup358-containing region wraps around the stems of both Y complexes, likely stabilizing the scaffold. Nup205 connects the short arms of the two Y complexes and associates with the stem of a neighbouring Y complex. The Nup214-containing region uses an extended coiled-coil to link Nup85 of the two Y complexes and protrudes into the axial pore of the NPC. These previously uncharacterized structural features reveal insights into NPC assembly.

biophysics↗

bioRxiv2020

Relative efficiencies of simple and complex substitution models in estimating divergence times in phylogenomics

The conventional wisdom in molecular evolution is to apply parameter-rich models of nucleotide and amino acid substitutions for estimating divergence times. However, the actual extent of the difference between time estimates produced by highly complex models compared to those from simple models is yet to be quantified for contemporary datasets that frequently contain sequences from many species and genes. In a reanalysis of many large multispecies alignments from diverse groups of taxa using the same tree topologies and calibrations, we found that the use of the simplest models can produce divergence time estimates and credibility intervals similar to those obtained from the complex models applied in the original studies. This result is surprising because the use of simple models underestimates sequence divergence for all the datasets analyzed. We find three fundamental reasons for the observed robustness of time estimates to model complexity in many practical datasets. First, the estimates of branch lengths and node-to-tip distances under the simplest model show an approximately linear relationship with those produced by using the most complex models applied, especially for datasets with many sequences. Second, relaxed clock methods automatically adjust rates on branches that experience considerable underestimation of sequence divergences, resulting in time estimates that are similar to those from complex models. And, third, the inclusion of even a few good calibrations in an analysis can reduce the difference in time estimates from simple and complex models. The robustness of time estimates to models complexity in these empirical data analyses is encouraging, because all phylogenomics studies use statistical models that are oversimplified descriptions of actual evolutionary substitution processes.

evolutionary biology↗

bioRxiv2019

Reliable confidence intervals for RelTime estimates of evolutionary divergence times

Confidence intervals (CIs) depict the statistical uncertainty surrounding evolutionary divergence time estimates. They capture variance contributed by the finite number of sequences and sites used in the alignment, deviations of evolutionary rates from a strict molecular clock in a phylogeny, and uncertainty associated with clock calibrations. Reliable tests of biological hypotheses demand reliable CIs. However, current non-Bayesian methods may produce unreliable CIs because they do not incorporate rate variation among lineages and interactions among clock calibrations properly. Here, we present a new analytical method to calculate CIs of divergence times estimated using the RelTime method, along with an approach to utilize multiple calibration uncertainty densities in these analyses. Empirical data analyses showed that the new methods produce CIs that overlap with Bayesian highest posterior density (HPD) intervals. In the analysis of computer-simulated data, we found that RelTime CIs show excellent average coverage probabilities, i.e., the true time is contained within the CIs with a 95% probability. These developments will encourage broader use of computationally-efficient RelTime approach in molecular dating analyses and biological hypothesis testing.

evolutionary biology↗

bioRxiv2019

Molecular dating for phylogenies containing a mix of populations and species

Concurrent molecular dating of population and species divergences is essential in many biological investigations, including phylogeography, phylodynamics, and species delimitation studies. Multiple sequence alignments used in these investigations frequently consist of both intra- and inter-species samples (mixed samples). As a result, the phylogenetic trees contain inter-species, inter-population, and within population divergences. To date these sequence divergences, Bayesian relaxed clock methods are often employed, but they assume the same tree prior for both inter- and intra-species branching processes and require specification of a clock model for branch rates (independent vs. autocorrelated rates models). We evaluated the impact of using the same tree prior on the Bayesian divergence time estimates by analyzing computer-simulated datasets. We also examined the effect of the assumption of independence of evolutionary rate variation among branches when the branch rates are autocorrelated. Bayesian approach with Skyline-coalescent tree priors generally produced excellent molecular dates, with some tree priors (e.g., Yule) performing the best when evolutionary rates were autocorrelated, and lineage sorting was incomplete. We compared the performance of the Bayesian approach with a non-Bayesian, the RelTime method, which does not require specification of a tree prior or selection of a clock model. We found that RelTime performed as well as the Bayesian approach, and when the clock model was mis-specified, RelTime performed slightly better. These results suggest that the computationally efficient RelTime approach is also suitable to analyze datasets containing both populations and species variation.

ecology↗

bioRxiv2018

Pervasive correlation of molecular evolutionary rates in the tree of life

New species arise from pre-existing species and inherit similar genomes and environments. This predicts greater similarity of mutation rates and the tempo of molecular evolution between direct ancestors and descendants, resulting in autocorrelation of evolutionary rates within lineages in the tree of life. Surprisingly, molecular sequence data have not confirmed this expectation, possibly because available methods lack power to detect autocorrelated rates. Here we present a machine learning method to detect the presence evolutionary rate autocorrelation in large phylogenies. The new method is computationally efficient and performs better than the available state-of-the-art methods. Application of the new method reveals extensive rate autocorrelation in DNA and amino acid sequence evolution of mammals, birds, insects, metazoans, plants, fungi, and prokaryotes. Therefore, rate autocorrelation is a common phenomenon throughout the tree of life. These findings suggest concordance between molecular and non-molecular evolutionary patterns and will foster unbiased and precise dating of the tree of life.

evolutionary biology↗

bioRxiv2017

RelTime relaxes the strict molecular clock throughout the phylogeny

The RelTime method estimates divergence times when evolutionary rates vary among lineages. Theoretical analyses show that RelTime relaxes the strict molecular clock throughout a molecular phylogeny, and it performs well in the analysis of empirical and computer simulated datasets in which evolutionary rates are variable. Lozano-Fernandez et al. (2017) found that the application of RelTime to one metazoan dataset (Erwin et al. 2011) produced equal rates for several ancient lineages, which led them to speculate that RelTime imposes a strict molecular clock for deep animal divergences. RelTime does not impose a strict molecular clock. The pattern observed by Lozano-Fernandez et al. (2017) was a result of the use of an option to assign the same rate to lineages in RelTime when the rates are not statistically significantly different. The median rate difference was 5% for many deep metazoan lineages for Erwin et al. (2011) dataset, so the rate equality was not rejected. In fact, RelTime analysis with and without the option to test rate differences produced very similar time estimates. We found that the Bayesian time estimates vary widely depending on the root priors assigned, and that the use of less restrictive priors produce Bayesian divergence times that are concordant with those from RelTime for Erwin et al. (2011) dataset. Therefore, it is prudent to discuss Bayesian estimates obtained under a range of priors in any discourse about molecular dating, including method comparisons.

evolutionary biology↗

bioRxiv2017

Theoretical foundation of the RelTime method for estimating divergence times from variable evolutionary rates

RelTime estimates divergence times by relaxing the assumption of a strict molecular clock in a phylogeny. It showed excellent performance in estimating divergence times for both simulated and empirical molecular sequence datasets in which evolutionary rates varied extensively throughout the tree. RelTime is computationally efficient and scales well with increasing size of datasets. Until now, however, RelTime has not had a formal mathematical foundation. Here, we show that the basis of the RelTime approach is a relative rate framework (RRF) that combines comparisons of evolutionary rates in sister lineages with the principle of minimum rate change between an evolutionary lineage and its descendants. We present analytical solutions for estimating relative lineage rates and divergence times under RRF. We also discuss the relationship of RRF with other approaches, including the Bayesian framework. We conclude that RelTime will be also useful for phylogenies with branch lengths derived not only from molecular data, but also morphological and biochemical traits.

evolutionary biology↗