Integrative Omics Reveals Rapidly Evolving Regulatory Sequences Driving Primate Brain Evolution.

Although the continual expansion of the brain during primate evolution accounts for our enhanced cognitive capabilities, the drivers of brain evolution have scarcely been explored in these ancestral nodes. Here, we performed large-scale comparative genomic, transcriptomic, and epigenomic analyses to investigate the evolutionary alterations acquired by brain genes and provide comprehensive listings of innovatory genetic elements along the evolutionary path from ancestral primates to human. The regulatory sequences associated with brain-expressed genes experienced rapid change, particularly in the ancestor of the Simiiformes. Extensive comparisons of single-cell and bulk transcriptomic data between primate and nonprimate brains revealed that these regulatory sequences may drive the high expression of certain genes in primate brains. Employing in utero electroporation into mouse embryonic cortex, we show that the primate-specific brain-biased gene BMP7 was recruited, probably in the ancestor of the Simiiformes, to regulate neuronal proliferation in the primate ventricular zone. Our study provides a comprehensive listing of genes and regulatory changes along the brain evolution lineage of ancestral primates leading to human. These data should be invaluable for future functional studies that will deepen our understanding not only of the genetic basis of human brain evolution but also of inherited disease.

Whole-genome sequence of the Tibetan frog Nanorana parkeri and the comparative evolution of tetrapod genomes.

The development of efficient sequencing techniques has resulted in large numbers of genomes being available for evolutionary studies. However, only one genome is available for all amphibians, that of Xenopus tropicalis, which is distantly related from the majority of frogs. More than 96% of frogs belong to the Neobatrachia, and no genome exists for this group. This dearth of amphibian genomes greatly restricts genomic studies of amphibians and, more generally, our understanding of tetrapod genome evolution. To fill this gap, we provide the de novo genome of a Tibetan Plateau frog, Nanorana parkeri, and compare it to that of X. tropicalis and other vertebrates. This genome encodes more than 20,000 protein-coding genes, a number similar to that of Xenopus. Although the genome size of Nanorana is considerably larger than that of Xenopus (2.3 vs. 1.5 Gb), most of the difference is due to the respective number of transposable elements in the two genomes. The two frogs exhibit considerable conserved whole-genome synteny despite having diverged approximately 266 Ma, indicating a slow rate of DNA structural evolution in anurans. Multigenome synteny blocks further show that amphibians have fewer interchromosomal rearrangements than mammals but have a comparable rate of intrachromosomal rearrangements. Our analysis also identifies 11 Mb of anuran-specific highly conserved elements that will be useful for comparative genomic analyses of frogs. The Nanorana genome offers an improved understanding of evolution of tetrapod genomes and also provides a genomic reference for other evolutionary studies.

Divergent Evolutionary Rates of Primate Brain Regions as Revealed by Genomics and Transcriptomics.

Although the primate brain contains numerous functionally distinct structures that have experienced diverse genetic changes during the course of evolution and development, these changes remain to be explored in detail. Here we utilize two classic metrics from evolutionary biology, the evolutionary rate index (ERI) and the transcriptome age index (TAI), to investigate the evolutionary alterations that have occurred in each area and developmental stage of the primate brain. We observed a higher evolutionary rate for those genes expressed in the non-cortical areas during primate evolution, particularly in human, with the highest rate of evolution being exhibited at brain developmental stages between late infancy and early childhood. Further, the transcriptome age of the non-cortical areas was lower than that of the cerebral cortex, with the youngest age apparent at brain developmental stages between late infancy and early childhood. Our exploration of the evolutionary patterns manifest in each brain area and developmental stage provides important reference points for further research into primate brain evolution.

Deciphering neo-sex and B chromosome evolution by the draft genome of Drosophila albomicans.

BACKGROUND: Drosophila albomicans is a unique model organism for studying both sex chromosome and B chromosome evolution. A pair of its autosomes comprising roughly 40% of the whole genome has fused to the ancient X and Y chromosomes only about 0.12 million years ago, thereby creating the youngest and most gene-rich neo-sex system reported to date. This species also possesses recently derived B chromosomes that show non-Mendelian inheritance and significantly influence fertility. METHODS: We sequenced male flies with B chromosomes at 124.5-fold genome coverage using next-generation sequencing. To characterize neo-Y specific changes and B chromosome sequences, we also sequenced inbred female flies derived from the same strain but without B's at 28.5-fold. RESULTS: We assembled a female genome and placed 53% of the sequence and 85% of the annotated proteins into specific chromosomes, by comparison with the 12 Drosophila genomes. Despite its very recent origin, the non-recombining neo-Y chromosome shows various signs of degeneration, including a significant enrichment of non-functional genes compared to the neo-X, and an excess of tandem duplications relative to other chromosomes. We also characterized a B-chromosome linked scaffold that contains an actively transcribed unit and shows sequence similarity to the subcentromeric regions of both the ancient X and the neo-X chromosome. CONCLUSIONS: Our results provide novel insights into the very early stages of sex chromosome evolution and B chromosome origination, and suggest an unprecedented connection between the births of these two systems in D. albomicans.

Ancestral developmental potentials in early bony fish contributed to vertebrate water-to-land transition.

The water-to-land transition was a major step in vertebrate evolution and eventually gave rise to the tetrapods, including amphibians, reptiles, birds, and mammals. The first land invasion of our fish ancestors is considered to have occurred during the late Devonian period ~370 million years ago (Daeschler et al., 2006). Many fossils from important transitional species, such as Tiktaalik, Acanthostega, and Ichthyostega, have helped to identify key morphological and anatomical structures crucial to vertebrate terrestrial adaptation (Coates, 1996; Johanson & Ahlberg, 2001; Shubin et al., 2006). However, homologous analyses of these body forms and structures in more ancient species have suggested that some of the morphologies related to vertebrate land dispersal were already present in early bony fish species. For instance, the presence of shoulder girdles on the articular surface of the endoskeleton in Late Lochkovian Psarolepis indicates that stem sarcopterygians already possessed an endoskeletal fin pattern similar to that of tetrapod stylopods (Zhu & Yu, 2009). In addition, primitive lungs, which originated from the respiratory pharynx and were located on the ventral side of the alimentary tracts, can be observed in several extant basal actinopterygians (bichirs, reedfish) and all extant sarcopterygians, as well as some fossils of coelacanths and salamanders (Cupello et al., 2017; Tissier et al., 2017) (Figure 1). This evidence suggests that, instead of relying on genetic innovations evolving after the first fish left their water habitat, this transition may have been accomplished by adopting physical traits and genetic components that already existed far earlier than when the transition occurred. Whether such an ancestral developmental regulatory network was present or not and how far this ancestral network can be traced in history are challenging questions for paleontologists. Three recent papers published in Cell provide new insights into this hypothesis. Wang et al. (2021) sequenced the giant genome of lungfish, the closest fish species to tetrapods, and Bi et al. (2021) sequenced the genomes of multiple early divergent ray-finned fish. Comparative genomic analyses from these two studies confirmed the presence of ancestral genetic regulatory networks that likely played essential roles in the development and evolution of various biological functions related to vertebrate land invasion. Although certain ancestral features have been lost in teleosts, the most derived fish lineage to evolve after whole-genome duplication (Sato & Nishida, 2010), they have been recreated in zebrafish by modifying their genetic makeup to reactivate the ancestral genetic network (Hawkins et al., 2021).

Dynamic evolution of transposable elements, demographic history, and gene content of paleognathous birds.

Palaeognathae includes ratite and tinamou species that are important for understanding early avian evolution. Here, we analyzed the whole-genome sequences of 15 paleognathous species to infer their demographic histories, which are presently unknown. We found that most species showed a reduction of population size since the beginning of the last glacial period, except for those species distributed in Australasia and in the far south of South America. Different degrees of contraction and expansion of transposable elements (TE) have shaped the paleognathous genome architecture, with a higher transposon removal rate in tinamous than in ratites. One repeat family, AviRTE, likely underwent horizontal transfer from tropical parasites to the ancestor of little and undulated tinamous about 30 million years ago. Our analysis of gene families identified rapid turnover of immune and reproduction-related genes but found no evidence of gene family changes underlying the convergent evolution of flightlessness among ratites. We also found that mitochondrial genes have experienced a faster evolutionary rate in tinamous than in ratites, with the former also showing more degenerated W chromosomes. This result can be explained by the Hill-Robertson interference affecting genetically linked W chromosomes and mitochondria. Overall, we reconstructed the evolutionary history of the Palaeognathae populations, genes, and TEs. Our findings of co-evolution between mitochondria and W chromosomes highlight the key difference in genome evolution between species with ZW sex chromosomes and those with XY sex chromosomes.

Author Correction: Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys.

Following the publication of our paper (Zhang et al., 2020), it has come to our attention that we erroneously listed two funding sources unrelated to this study in the "ACKNOWLEDGEMENTS" section. Hereby, we wish to update the "ACKNOWLEDGEMENTS" section as a correction.

Genome and single-cell RNA-sequencing of the earthworm Eisenia andrei identifies cellular mechanisms underlying regeneration.

The earthworm is particularly fascinating to biologists because of its strong regenerative capacity. However, many aspects of its regeneration in nature remain elusive. Here we report chromosome-level genome, large-scale transcriptome and single-cell RNA-sequencing data during earthworm (Eisenia andrei) regeneration. We observe expansion of LINE2 transposable elements and gene families functionally related to regeneration (for example, EGFR, epidermal growth factor receptor) particularly for genes exhibiting differential expression during earthworm regeneration. Temporal gene expression trajectories identify transcriptional regulatory factors that are potentially crucial for initiating cell proliferation and differentiation during regeneration. Furthermore, early growth response genes related to regeneration are transcriptionally activated in both the earthworm and planarian. Meanwhile, single-cell RNA-sequencing provides insight into the regenerative process at a cellular level and finds that the largest proportion of cells present during regeneration are stem cells.

Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys.

Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys ( Macacafascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3ß,5,6ß-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.

Chromosomal level assembly and population sequencing of the Chinese tree shrew genome.

Chinese tree shrews (Tupaia belangeri chinensis) have become an increasingly important experimental animal in biomedical research due to their close relationship to primates. An accurately sequenced and assembled genome is essential for understanding the genetic features and biology of this animal. In this study, we used long-read single-molecule sequencing and high-throughput chromosome conformation capture (Hi-C) technology to obtain a high-qualitychromosome-scale scaffolding of the Chinese tree shrew genome. The new reference genome (KIZ version 2: TS_2.0) resolved problems in presently available tree shrew genomes and enabled accurate identification of large and complex repeat regions, gene structures, and species-specific genomic structural variants. In addition, by sequencing the genomes of six Chinese tree shrew individuals, we produced a comprehensive map of 12.8 M single nucleotide polymorphisms and confirmed that the major histocompatibility complex (MHC) loci and immunoglobulin gene family exhibited high nucleotide diversity in the tree shrew genome. We updated the tree shrew genome database (TreeshrewDB v2.0: http://www.treeshrewdb.org) to include the genome annotation information and genetic variations. The new high-quality reference genome of the Chinese tree shrew and the updated TreeshrewDB will facilitate the use of this animal in many different fields of research.

Evolutionary trajectories of snake genes and genomes revealed by comparative analyses of five-pacer viper.

Snakes have numerous features distinctive from other tetrapods and a rich history of genome evolution that is still obscure. Here, we report the high-quality genome of the five-pacer viper, Deinagkistrodon acutus, and comparative analyses with other representative snake and lizard genomes. We map the evolutionary trajectories of transposable elements (TEs), developmental genes and sex chromosomes onto the snake phylogeny. TEs exhibit dynamic lineage-specific expansion, and many viper TEs show brain-specific gene expression along with their nearby genes. We detect signatures of adaptive evolution in olfactory, venom and thermal-sensing genes and also functional degeneration of genes associated with vision and hearing. Lineage-specific relaxation of functional constraints on respective Hox and Tbx limb-patterning genes supports fossil evidence for a successive loss of forelimbs then hindlimbs during snake evolution. Finally, we infer that the ZW sex chromosome pair had undergone at least three recombination suppression events in the ancestor of advanced snakes. These results altogether forge a framework for our deep understanding into snakes' history of molecular evolution.

[Economic burden and related factors on inpatients with HBV-related diseases in Shandong province].

OBJECTIVE: To investigate the economic burden of patients with acute and chronic hepatitis B, cirrhosis and liver cancer caused by hepatitis B virus (HBV). METHODS: Cluster sampling was used on cases consecutively collected during the study period. Questionnaire survey was conducted and information on the expenses during hospitalization was collected from the hospital records and through interviewing those patients. RESULTS: Yearly costs related to patients with acute hepatitis B, severe hepatitis B, chronic hepatitis B, cirrhosis, hepatocellular carcinoma were 66.7, 138.1, 127.4, 151.7 and 377.2 thousand Yuan, respectively. RESULTS: from multiple linear regression model showed that the type of medical insurance scheme, annual days of hospitalization, classifications of HBV-related diseases and personal income were major influencing factors on the cost. CONCLUSION: HBV infection caused considerable burden to families and the society, indicating that HBV infection control programs would bring huge potential benefits. The reform of insurance scheme should be administrated to promote social fairness.

Genome of the Chinese tree shrew.

Chinese tree shrews (Tupaia belangeri chinensis) possess many features valuable in animals used as experimental models in biomedical research. Currently, there are numerous attempts to employ tree shrews as models for a variety of human disorders: depression, myopia, hepatitis B and C virus infections, and hepatocellular carcinoma, to name a few. Here we present a publicly available annotated genome sequence for the Chinese tree shrew. Phylogenomic analysis of the tree shrew and other mammalians highly support its close affinity to primates. By characterizing key factors and signalling pathways in nervous and immune systems, we demonstrate that tree shrews possess both shared common and unique features, and provide a genetic basis for the use of this animal as a potential model for biomedical research.