Biology subjects

Zhou, Q.

Publications and source records attributed to Zhou, Q..

At least 289 records · Page 16Linked to original sources

bioRxiv2019

Female-specific and dosage selections restore genes through transpositions onto the degenerated songbird W chromosomes

Sex chromosomes are usually suppressed for homologous recombination, which leads to the loss of functional genes on the Y or W chromosomes. It remains unclear how species like birds with a ZW sex system cope with the consequential gene expression imbalance, usually in the absence of global dosage compensation mechanism. Here we tackle this conundrum by reporting 14 genes recently transposed from the Z to the W chromosomes of three songbird lineages, after analyzing a total of 12 songbird species genomes. These transpositions are estimated to have occurred within 9 million years. Besides the expected signatures of functional degeneration in some genes on the non-recombining W chromosomes, the other retained genes after transposition are enriched for haploinsufficient genes or housekeeping genes. Several genes show biased expression in ovaries of birds or lizard, or function in female germ cells. These results, together with the reported X-to-Y transpositions provide direct evidence that sex-specific and dosage selections may have recurrently driven the restoration of genes on the Y or W chromosomes, and suggest their evolutionary processes are more dynamic than simply becoming completely degenerated.

evolutionary biology↗

bioRxiv2019

The NALCN regulator UNC-80 functions in a subset of interneurons to affect C. elegans avoidance response to the plant hormone methyl salicylate.

NALCN (Na+ leak channel, non-selective), UNC80 and UNC79 form a non-selective, voltage-independent cation channel complex that affects a broad array of neuronal activities. The molecular and neuronal mechanisms underlying the functions of the NALCN complex remain unclear. In a screen for Caenorhabditis elegans mutants with defective avoidance response to the plant hormone methyl salicylate (MeSa), we isolated novel loss-of-function (lf) mutations in unc-80 and unc-79. unc-80 and unc-79 lf mutants exhibited defective MeSa avoidance but wild type-like responses to other odorants. Lf mutants of C. elegans nca/NALCN exhibited similar MeSa-specific avoidance defect, while lf mutants of the NALCN regulatory gene nlf-1 avoided MeSa like wild type. Using fluorescent transgenic animals, we identified a subset of unc-80-expressing neurons. Neuron-specific transgene rescue and knockdown experiments suggest that a subset of interneurons, primarily including AVA, AVE and AVG, might play a necessary and sufficient role in mediating unc-80 regulation of the MeSa avoidance. We found that unc-79 was expressed in neurons largely overlapping those expressing unc-80, which is supported by the rescue of unc-80(lf) defects using an unc-80 transgene driven by an unc-79 promoter. We also suggest that C. elegans locomotion responds more sensitively to the changes of expression levels of NALCN-related genes than the MeSa avoidance does. Together, our results identified NALCN-related genes as key regulators of the MeSa avoidance behavior and provided novel genetic and neuronal insights into the function of the NALCN channel complex.\n\nAuthor summaryNALCN (Na+ leak channel, non-selective) is a non-selective, voltage-independent cation channel that affects multiple neuronal activities and behaviors. Mutations in NALCN and its regulator UNC80 can cause serious neurological diseases. The regulation and function of the NALCN channel complex remain to be understood. From a genetic screen, we surprisingly found that the nematode Caenorhabditis elegans requires NALCN and its two regulators UNC-80 and UNC-79 to escape from the plant stress hormone methyl salicylate (MeSa). Using methods including transgenic neuronal labeling, rescues and knockdowns, we found that unc-80-expression in a subset of head interneurons, including AVA, AVE and AVG, might be necessary and sufficient to elicit the MeSa avoidance response. We also found that unc-79 functions in overlapping neurons as unc-80 to regulate C. elegans behaviors. Our findings provide novel molecular and neuronal mechanisms for understanding the regulation and function of the NALCN channel complex.

genetics↗

bioRxiv2019

Phase separation of TAZ compartmentalizes the transcription machinery to promote gene expression

TAZ promotes cell proliferation, development, and tumorigenesis by regulating target gene transcription. However, how TAZ orchestrates the transcriptional responses remains poorly defined. Here we demonstrate that TAZ forms nuclear condensates via liquid-liquid phase separation to compartmentalize its DNA binding co-factor TEAD4, the transcription co-activators BRD4 and MED1 and the transcription elongation factor CDK9 for activation of gene expression. TAZ, but not its paralog YAP, forms phase-separated droplets in vitro and liquid-like nuclear condensates in vivo, and this ability is negatively regulated by Hippo signaling via LATS-mediated phosphorylation and mediated by the coiled-coil domain. Deletion of the TAZ coiled-coil domain or substitution with the YAP coiled-coil domain does not affect the interaction of TAZ with its partners, but prevents its phase separation and more importantly, its ability to induce target gene expression. Thus, our study identifies a novel mechanism for the transcriptional activation by TAZ and demonstrates for the first time that pathway-specific transcription factors also engage the phase separation mechanism for efficient transcription activation.

cell biology↗

bioRxiv2019

Chromatin interaction analysis with updated ChIA-PET Tool (V3)

Understanding chromatin interactions is important since they create chromosome conformation and link the cis- and trans-regulatory elements to their target genes for transcriptional regulation. Chromatin Interaction Analysis with Paired-End Tag (ChIA-PET) sequencing is a genome-wide high-throughput technology that detects chromatin interactions associated with a specific protein of interest. Previously we developed ChIA-PET Tool in 2010 for ChIA-PET data analysis. Here we present the updated version of ChIA-PET Tool (V3), is a computational package to process the next-generation sequence data generated from ChIA-PET experiments. It processes the short-read data and long-read ChIA-PET data with multithreading and generates the statistics of results in a HTML file. In this paper, we provide a detailed demonstration of the design of ChIA-PET Tool V3 and how to install it and analyze a specific ChIA-PET data set with it. At present, other ChIA-PET data analysis tools have developed including ChiaSig, MICC, Mango and ChIA-PET2 and so on. We compared our tool with other tools using the same public data set in the same machine. Most of peaks detected by ChIA-PET Tool V3 overlap with those from other tools. There is higher enrichment for significant chromatin interactions of ChIA-PET Tool V3 in APA plot. ChIA-PET Tool V3 is open source and is available at GitHub (https://github.com/GuoliangLi-HZAU/ChIA-PET_Tool_V3/).

genomics↗

bioRxiv2019

Perinatal features of Prader-Willi syndrome: a Chinese cohort

BackgroundPrader-Willi syndrome (PWS) is a rare complex genetic disorder caused by an absence of expression of imprinted genes on the paternally derived chromosome 15q11-q13 region. This study aimed to characterize the perinatal features in a cohort of Chinese individuals with PWS.\n\nMethodsWe analyzed anonymous data of 134 patients from the PWS Registry in China. Perinatal and neonatal presentations were analyzed, and compared between the two PWS genetic subtypes. We also compared the perinatal features of PWS patients with the general population and other previous reported large cohorts from France, UK and USA.\n\nResultsThis study included 134 patients with PWS (115 patients with 15q11-q13 deletion and 19 with maternal UPD). High mean maternal age was found in this cohort (30.5 vs. 26.7) comparing with the general population. 88.6% of mothers reported a decrease of fetal movements. 42.5% and 18.7% of mothers had polyhydramnios and oligohydramnios during pregnancy, respectively. 82.8% of the patients were born by caesarean section. 32.1% of neonates had birth asphyxia, 98.5% had hypotonia and 97.8% had weak cry or even no cry at neonatal period. Feeding difficulty existed in 99.3% of the infants, and 94.8% of them had failure to thrive. 69.4% of the infants ever used feeding tube during hospitalization. However, 97.8% of them discontinued tube feeding after discharged home. Maternal age, maternal pre-pregnancy weight and BMI were significantly higher in the UPD group (all P<0.05).\n\nConclusionsPWS should be highlighted for differential diagnosis for infants with following perinatal factors including polyhydramnios, intrauterine decreased fetal movements, cesarean section, low birth weight, feeding difficulty, hypotonia, and failure to thrive. Higher maternal age may be a risk factor for PWS, especially for UPD, and further studies for the mechanism of PWS are required.\n\nAuthor SummaryEarly diagnosis and tailored multidisciplinary treatment are utmost important for better quality of life of the infants with Prader-willi syndrome. Genetic diagnosis for PWS is now easily available; and diagnosis can be made in most patients within the first months of life even prenatally if obstetricians or neonatologists can recognize the perinatal features of PWS well. However, most patients still had a late diagnosis because the early signs of PWS not recognized. Our study highlighted the perinatal features of a large cohort of Chinese patients with PWS, which will benefit for early diagnosis and treatment. We found high incidence of decreased fetal movements, polyhydramnios and delivery by cesarean section, and higher maternal age comparing with the general population. Neonatal features found in our cohort included low birth weight, birth asphyxia, failure to thrive, feeding difficulty, weak cry and hypotonia. We found mothers with UPD had higher maternal age, pre-pregnancy weight and BMI. Most patients required tube feeding during hospitalization, however tube feeding was discontinued by their parents after discharge at home. Nutrition deficiency was a serious problem in infants with PWS. Home tube-feeding instruction should be carried out for parents of PWS patients in China.

genetics↗

bioRxiv2018

Inference of tumor cell-specific transcription factor binding from cell-free DNA

Alterations in transcription factors are important drivers of tumorigenesis, but non-invasive assays for assessing transcription factor activity are lacking. Here, we evaluated the feasibility of inferring transcription factor binding in solid tumors from their nucleosome footprint in circulating cell-free DNA. We developed a novel analysis pipeline to determine accessibility of transcription factor binding sites and applied it to 244 cell-free DNA samples from patients with prostate, breast and colon cancer. We observed patient-specific as well as tumor-specific patterns. Specifically, inferred binding patterns for the transcription factors AR, HOXB13, and NKX3-1 allowed us to classify patients by tumor type, including subtypes of prostate cancer, which has clinical implications for the management of patients. Our approach for mapping tumor-specific transcription factor binding in vivo based on blood samples makes a key part of the noncoding genome amenable for clinical analysis.

cancer biology↗

bioRxiv2018

Dynamic evolutionary history and gene content of sex chromosomes across diverse songbirds

Songbirds have a species number almost equivalent to that of mammals, and are classic models for studying mechanisms of speciation and sexual selection. Sex chromosomes are hotspots of both processes, yet their evolutionary history in songbirds remains unclear. To elucidate that, we characterize female genomes of 11 songbird species having ZW sex chromosomes, with 5 genomes of bird-of-paradise species newly produced in this work. We conclude that songbird sex chromosomes have undergone at least four steps of recombination suppression before their species radiation, producing a gradient pattern of pairwise sequence divergence termed evolutionary strata. Interestingly, the latest stratum probably emerged due to a songbird-specific burst of retrotransposon CR1-E1 elements at its boundary, or chromosome inversion on the W chromosome. The formation of evolutionary strata has reshaped the genomic architecture of both sex chromosomes. We find stepwise variations of Z-linked inversions, repeat and GC contents, as well as W-linked gene loss rate that are associated with the age of strata. Over 30 W-linked genes have been preserved for their essential functions, indicated by their higher and broader expression of orthologs in lizard than those of other sex-linked genes. We also find a different degree of accelerated evolution of Z-linked genes vs. autosomal genes among different species, potentially reflecting their diversified intensity of sexual selection. Our results uncover the dynamic evolutionary history of songbird sex chromosomes, and provide novel insights into the mechanisms of recombination suppression.

evolutionary biology↗

bioRxiv2018

The Histone Demethylase KDM4D Promotes Hepatic Fibrogenesis by Modulating Toll-Like Receptor 4 Signaling Pathway

Accumulating evidence has revealed the pivotal role of epigenetic regulation in the pathogenesis of liver disease. However, the epigenetic mechanism that accounts for hepatic stellate cells (HSCs) activation in liver fibrosis remains largely unknown. In this study, primary HSCs were used to screen the differentially expressed histone H3 lysine methyltransferases and demethylases during HSC activation. KDM4D was identified as a remarkable up-regulated histone H3 demethylase during HSC activation. The overexpression profile of KDM4D was further confirmed in three fibrosis animal models and human fibrotic liver tissues. In vitro genetic silencing of Kdm4d impaired the collagen gel contraction and migration capacity of primary HSCs. In established CCl4-induced mice model, Kdm4d knockdown inhibited fibrosis progression, and promoted fibrosis reversal, with enhanced thinning and splitting of fibrotic septa, as well as a dramatic decrease in collagen area. Whole gene transcriptome analysis showed the regulatory role of KDM4D in Toll-Like Receptor (TLR) signaling pathway. Mechanistically, KDM4D catalyzed histone 3 on lysine 9 (H3K9) di-, and tri-demethylation, which promoted TLR4 expression, and subsequently prompted liver fibrogenesis by activating NF-{kappa}B signaling pathways. KDM4D facilitates TLR4 transcription through demethylation of H3K9, thus activating TLR4/NF-{kappa}B signaling pathways in HSCs, contributing to HSC activation and collagen crosslinking, further, hepatic fibrosis progression.

cell biology↗

bioRxiv2018

Cyclin B3 is specifically required for metaphase to anaphase transition in mouse oocyte meiosis I

Meiosis, a cell division to generate gametes for sexual reproduction in eukaryotes, executes a single round of DNA replication and two successive rounds of chromosome segregation [1]. The extraordinary reliability of the meiotic cycle requires the activities of cyclin-dependent kinases (Cdks) associated with specific cyclins [2-4]. Cyclins are the regulatory subunits of protein kinases, which are the main regulators of maturation promoting factor or mitosis promoting factor (MPF) [5, 6] and anaphase-promoting complex/cyclosome (APC/C) [7, 8] in eukaryotic cell division. But how cyclins collaborate to control meiosis is still largely unknown. Cyclin B3 (Ccnb3) shares homology with A- and B-type cyclins [9], and is conserved during higher eukaryote evolution [10-17]. Previous studies have shown that Ccnb3-deleted females are sterile with oocytes unable to complete meiosis I in Drosophila [18], implying that Ccnb3 may have a special role in meiosis. To clarify the function of Ccnb3 in meiosis in mammalian species, we generated Ccnb3 mutant mice by CRISPR/Cas9, and found that Ccnb3 mutation caused female infertility with the failure of metaphase-anaphase transition in meiosis I. Ccnb3 was necessary for APC/C activation to initiate anaphase I, but not required for oocytes maturation, meiosis II progression, or early embryonic development. Our study reveals the differential cell cycle regulation between meiosis I and meiosis II, as well as meiosis between males and females, which shed light on the cell cycle control of meiosis.\n\nHighlightsO_LIIdentification of a female meiosis-specific cyclin in mouse\nC_LIO_LICyclin B3 is required for metaphase-anaphase transition in oocyte meiosis I\nC_LIO_LICyclin B3 is not essential for oocyte maturation and sister chromosome segregation\nC_LIO_LICyclin B3 is necessary for APC/C activation and MPF kinase activity through Cdk1\nC_LI

cell biology↗

bioRxiv2018

Single-cell RNA-seq reveals distinct dynamic behavior of sex chromosomes during early human embryogenesis

AbstractO_ST_ABSBackgroundC_ST_ABSSeveral animal and human studies have demonstrated that sex affects kinetics and metabolism during early embryo development. However, the mechanism governing these differences at the molecular level is unknown, warranting a systematic profiling of gene expression in males and females during embryogenesis.\n\nFindingsWe performed comprehensive analyses of gene expression comparing male and female embryos using available single-cell RNA-sequencing data of 1607 individual cells from 99 human preimplantation embryos, covering development stages from 4-cell to late blastocyst (E2 to E7). Consistent chromosome-wide transcription of autosomes was observed, while sex chromosomes showed significant differences after embryonic genome activation (EGA). Differentially expressed genes (DE genes) in male and female embryos mainly involved in the cell cycle, protein translation and metabolism. The Y chromosome was initially activated by pioneer genes, RPS4Y1 and DDX3Y, while the two X chromosomes in female were widely activated after EGA. Expression of X-linked genes in female significantly declined at the late blastocyst stage, especially in trophectoderm cells, revealing a rapid process of dosage compensation.\n\nConclusionsWe observed imbalanced expression from sex chromosomes in male and female embryos during EGA, with dosage compensation occurring first in female trophectoderm cells. Studying the effect of sex differences during human embryogenesis, as well as understanding the mechanism of X chromosome inactivation and its correlation with early miscarriage, will provide a basis for advancing assisted reproductive technology (ART) and thereby improve the treatment of infertility and possibly enhance reproductive health.

developmental biology↗

bioRxiv2018

Comprehensive analysis of immune evasion in breast cancer by single-cell RNA-seq

The tumor microenvironment is composed of numerous cell types, including tumor, immune and stromal cells. Cancer cells interact with the tumor microenvironment to suppress anticancer immunity. In this study, we molecularly dissected the tumor microenvironment of breast cancer by single-cell RNA-seq. We profiled the breast cancer tumor microenvironment by analyzing the single-cell transcriptomes of 52,163 cells from the tumor tissues of 15 breast cancer patients. The tumor cells and immune cells from individual patients were analyzed simultaneously at the single-cell level. This study explores the diversity of the cell types in the tumor microenvironment and provides information on the mechanisms of escape from clearance by immune cells in breast cancer.\n\nOne Sentence SummaryLandscape of tumor cells and immune cells in breast cancer by single cell RNA-seq

cancer biology↗

bioRxiv2018

The contrasting response to drought and waterlogging is underpinned by divergent DNA methylation programs associated with gene expression in sesame

DNA methylation is a heritable epigenetic mechanism that participates in gene regulation under abiotic stresses in plants. Sesame (Sesamum indicum L.) is typically considered a drought-tolerant crop but highly susceptible to waterlogging, a property attributed to its presumed origin in Africa or India. Understanding DNA methylation patterns in sesame under drought and waterlogging conditions can provide insights into the regulatory mechanisms underlying its contrasting responses to these principal abiotic stresses. Here, we combined Methylation-Sensitive Amplified Polymorphism and transcriptome analyses to profile cytosine methylation patterns, gene expression alteration, and their interplay in drought-tolerant and waterlogging-tolerant sesame genotypes under control, stress and recovery conditions. Our data showed that drought stress strongly induced de novo methylation (DNM) whereas most of the loci were demethylated (DM) during the recovery phase. In contrast, waterlogging decreased the level of methylation under stress but during the recovery phase, both DM and DNM were concomitantly deployed. In both stresses, the differentially expressed genes (DEGs) were highly correlated with the methylation patterns. We observed that DM was associated with the up-regulation of the DEGs while DNM was correlated with the down-regulation of the DEGs. In addition, we sequenced 44 differentially methylated regions of which 90% overlapped with the promoters and coding sequences of the DEGs. Altogether, we demonstrated that sesame has divergent epigenetic programs that respond to drought and waterlogging stresses. Our results also highlighted the possible interplay among DNA methylation and gene expression, which may modulate the contrasting responses to drought and waterlogging in sesame.

plant biology↗

bioRxiv2018

How do wind speed, release height, seed morphology interact to determine seed dispersal trajectory of Calligonum (Polygonaceae) species

How seed dispersal trajectory shifts with abiotic and biotic factors and what is the relationship between seed dispersal distance and dispersal trajectory are remain unclear. We used wind tunnel and video camera to track the seed dispersal trajectory of 7 Calligonum species with different appendages under the different wind speeds and the release heights. Dispersal trajectories and distances were determined by video analysis and spatial coordinate transformation. Based on perspective principle, 4 modes of trajectories were determined. Wind speed, seed mass and release height were the key factors determining seed dispersal trajectory modes. Release height and wind speed tended to have the strongest explanatory power on seeds with bristles and wings, respectively. Different trajectory modes lead to different dispersal distance, while the same dispersal distance can be the result of different trajectory modes. The proportion of species trajectory modes formed its trajectory spectrum. Wind speed tends to have strong influence on light and low-wind-loading seeds, release height tends to have that on heavy and high-wind-loading seeds. Species with high proportion of horizontal projectile and projectile have high dispersal capacity, vice versa. Therefore, trajectory spectrum of a species reveals its primary dispersal strategies and evolutionary consequences.

ecology↗

bioRxiv2018

Structure simulation of thrombopoietin receptor C-MPL with missense SNPs and its geographical distribution

Mpl is a key gene controlling the process of proliferation and differentiation of megakaryocyte and several studies reported that the mutation of mpl will even cause accurate megakaryocyte leukemia. By overlapping the missense mutation in NCBI and recorded SNP in 1000 genome database, we sorted out 4 SNPs(rs190983971, rs563996763, rs546510242, rs373621350) to find out its conformational changes. With Phyre v2.0, we simulated the secondary and tertiary structure change caused by the SNP and compared it with the original structure. The significant changes indicated its potential in leading to diseases associated with platelet reproduction. Finally, according to 1000 genome database, we constructed the geographically distribution of different populations and its SNPs carrying rate.

bioinformatics↗

bioRxiv2018

Deconvolution of single-cell multi-omics layers reveals regulatory heterogeneity

Integrative analysis of multi-omics layers at single cell level is critical for accurate dissection of cell-to-cell variation within certain cell populations. Here we report scCAT-seq, a technique for simultaneously assaying chromatin accessibility and the transcriptome within the same single cell. We show that the combined single cell signatures enable accurate construction of regulatory relationships between cis-regulatory elements and the target genes at single-cell resolution, providing a new dimension of features that helps direct discovery of regulatory patterns specific to distinct cell identities. Moreover, we generated the first single cell integrated maps of chromatin accessibility and transcriptome in human pre-implantation embryos and demonstrated the robustness of scCAT-seq in the precise dissection of master transcription factors in cells of distinct states during embryo development. The ability to obtain these two layers of omics data will help provide more accurate definitions of \"single cell state\" and enable the deconvolution of regulatory heterogeneity from complex cell populations.

genomics↗

bioRxiv2018

Destabilization of Ran C-terminus promotes GTP loading and occurs in multiple Ran cancer mutations

Ran (Ras-related nuclear protein) plays several important roles in nucleo-cytoplasmic transport, mitotic spindle formation, nuclear envelope/nuclear pore complex assembly, and other diverse functions in the cytoplasm, as well as in cellular transformation when activated. Unlike other Ras superfamily proteins, Ran contains an auto-inhibitory C-terminal tail, which packs against its G domain and bias Ran towards binding GDP over GTP. The biological importance of this C-terminal tail is not well understood. By disrupting the interaction between the C-terminus and the G domain, we were able to generate Ran mutants that are innately active and potently bind to RanBP1 (Ran Binding Protein 1), nuclear export factor CRM1 and nuclear import factor KPNB1. In contrast to previously reported activated Ran mutants, the C-terminus destabilized mutants are hydrolysis competent in cells, support nuclear transport, and do not form nuclear rim staining. Crystal structures show that one of these C-terminal mutations slightly changes its mode of binding to RanBP1. Finally, a high percentage of Ran C-terminus mutations from cancer patients were found to be destabilizing and hyperactivating, suggesting that Ran C-destabilization might be an unprecedented cellular transformation mechanism in affected cancers. This study also highlights a new drug design strategy towards treating patients with hyperactivated Ras proteins including K-Ras.

biochemistry↗

bioRxiv2018

Distinct RanBP1 nuclear export and cargo dissociation mechanisms between fungi and animals

Ran binding protein 1 (RanBP1), the primary effector of nuclear GTPase Ran, is a cytoplasmic-enriched and nuclear-cytoplasmic shuttling protein, playing important roles in nuclear transport through preventing RanGTP from being trapped with karyopherin proteins and dissociating cargoes from nuclear export factor CRM1. Much of what we know about RanBP1 is learned from fungi. Here we show that animal RanBP1 has distinct cargo dissociation and nuclear export mechanisms. In contrast to CRM1-RanGTP sequestration mechanism of cargo dissociation in fungi, animal RanBP1 solely sequesters RanGTP from nuclear export complexes. In fungi, RanBP1, CRM1 and RanGTP form a 1:1:1 nuclear export complex; in contrast, animal RanBP1, CRM1 and RanGTP form a 1:1:2 nuclear export complex. The key feature for the two mechanistic changes from fungi to animals is the loss of affinity between RanBP1-RanGTP and CRM1, since residues mediating their interaction in fungi are not conserved in animals. The biological significances of these different mechanisms in fungi and animals are also studied and discussed. Our study illustrates how orthologous proteins may play conserved functions through distinct routes, and may provide directions for design of antifungal medicines.

biochemistry↗

bioRxiv2018

On the regulatory evolution of new genes throughout their life history

Every gene has a birthplace and an age, i.e., a cis-regulatory environment and an evolution lifespan since its origination, yet how genes evolution trajectory is shaped by the two remains unclear. Here we address this basic question by comparing phylogenetically dated new genes of different ages among Drosophila and vertebrate species. For both, we find a clear out of testis transition from the testis-specific young genes to the broadly expressed old housekeeping genes. Particularly, many new genes have evolved specific activation at maternal-zygotic transition, or distinctive spatiotemporal embryonic expression patterns from the parental genes. We uncover an age-dependent gain/loss of active/repressive histone modifications and cis-regulatory elements, with variations between species and between somatic/germline tissues, which together underpin the stepwise acquisition of novel and important function by new genes. These results illuminate the general evolution trajectory and the underlying regulatory mechanisms of genes throughout their life history.

evolutionary biology↗