Genome Biology最新文献

Background: The jaguar (Panthera onca) is a keystone species within diverse ecosystems ranging from dense rainforests to open grasslands across Central and South America. However, its populations are declining rapidly due to anthropogenic actions, such as deforestation and poaching. Here we investigate the effects of this decline on genetic diversity and genetic health. Utilizing both modern and historical museum samples, we infer population structure and immunome variability in 25 jaguars to identify unique genetic diversity that can inform targeted conservation efforts.

Results: Our genome-wide analyses identifies three distinct geographic populations: Central America, South American lowlands, and South American highlands. Modern samples that exhibit lower levels of heterozygosity also show higher levels of inbreeding. The South American lowland population shows the lowest levels of inbreeding, while the highland population exhibits the lowest overall immunome-wide variability. However, the innate (Natural Killer Cell Complex, Toll-Like Receptor) and adaptive (Major Histocompatibility Complex Class II) immune genes, which are crucial for adaptive responses and disease resilience, show high diversity in terms of heterozygosity and haplotype diversity in individuals of all three populations.

Conclusions: South American highland and Central American jaguars face significant threats from habitat loss and fragmentation. The observed genome- and immunome-wide diversity in historical and modern jaguars reflect their recent demographic decline and challenges of local adaptation. We recommend re-evaluating evolutionarily significant units to prioritize conservation strategies, ensuring the preservation of unique genetic and adaptive diversity crucial for the species' resilience and long-term survival.

Background: Many transcript isoforms generated by intronic polyadenylation (IPA) encode isoforms of canonical proteins. Microproteins are an emerging class of small proteins translated from small open reading frames (sORFs) in noncoding RNAs and mRNAs, but their production by IPA isoforms is unknown.

Results: Here, by crossing 3'-seq, Ribo-Seq, and mass-spectrometry data, we identify 297 genes with a microprotein-coding IPA isoform terminating in a 5'UTR intron (coined miP-5'UTR-IPA isoform). By 3'-seq and long-read RNA-seq analyses in lung cancer cells treated with cisplatin, a DNA-cross-linking anticancer drug, we find that cisplatin globally favors the expression of (miP-5'UTR-)IPA isoforms relative to full-length mRNAs, mainly by decreasing the latter through an inhibition of transcription processivity in a FANCD2 and senataxin-dependent manner. The cisplatin-regulated miP-5'UTR-IPA isoform in the PRKAR1B gene is translated, as it is associated with light polysome fractions and contains Ribo-Seq-supported sORFs in its alternative last exon, and the microprotein (PRKAR1B-IPA-miP2) encoded by its sORF#2 is detected by Western blot and immunofluorescence. CRISPR editing of either the IPA site or the sORF#2 initiation site leads to decreased cell growth inhibition by cisplatin and camptothecin, another genotoxic drug. Mechanistically, PRKAR1B-IPA-miP2 promotes p53 protein induction by cisplatin. Finally, 70 miP-5'UTR-IPA isoforms are detected in normal cells, and 143 are upregulated by cisplatin.

Conclusions: Here, we show that IPA isoforms are a novel source of microproteins, and we reveal the novel paradigm of miP-5'UTR-IPA genes that produce both a canonical full-length mRNA and a microprotein-coding IPA isoform.

Shotgun metagenomics holds great potential for identifying parasite DNA in biological samples, but its effectiveness is limited by widespread contamination in publicly available reference genomes, which hinders accurate detection. In this study, we systematically quantify and remove contamination from 831 published endoparasite genomes to create ParaRef, a curated reference database for species-level parasite detection. We show that decontamination significantly reduces false detection rates and improves overall detection accuracy. Our study highlights the pervasive issue of contamination in public databases and offers a resource that will enhance the reliability of parasite detection using metagenomics.

Background: The birth of new genes from non-coding sequences has been postulated to be preceded by a proto-gene phase, in which a sequence is translated into protein but does not exhibit hallmarks of a clear function. Despite the abundance of such proto-genes in bacterial genomes, the frequency of their emergence and whether they actually act as precursors of new genes in natural populations are still open questions.

Results: To address these issues, we applied a combination of transcriptomic, proteomic, and comparative genomic approaches to identify and analyze hundreds of novel bacterial protein-coding genes that have previously escaped annotation. These novel proteins, including many that are widely conserved across genera, display sequence properties indistinguishable from the non-coding regions of the genome, suggesting that the vast majority are evolving neutrally. Despite their abundance and high degree of taxonomic restriction, we were only able to rigorously establish the de novo emergence of one proto-gene within the history of Escherichia coli, highlighting the difficulty of detecting this mode of gene birth in bacterial genomes. Contrary to expectations, we discover that proto-genes emerge at a uniform rate across distant bacterial taxa despite significant differences in their genomic characteristics, suggesting the presence of taxon-specific mechanisms that regulate their origination and persistence.

Conclusions: Overall, our findings indicate that proto-genes regularly emerge in bacterial populations but that their sequence properties furnish little evidence that they serve as precursors to new genes.

We present iNOMe-seq, a novel method for in vivo simultaneous profiling of chromatin accessibility, nucleosome occupancy, DNA-binding protein sites, and DNA methylation in living tissues. iNOMe-seq utilizes an ^m5C methyltransferase to mark accessible cytosines in a GpC context, bypassing nucleosome-restricted regions. Using Arabidopsis thaliana, we demonstrate that iNOMe-seq improves chromatin accessibility quantification compared to existing methods. Furthermore, it allows for the spatial and temporal analysis of chromatin dynamics, transcription factor binding, and DNA methylation, offering insight into the role of epigenetic components in transcriptional regulation across tissues and genetic variations in natural populations.

Developing glycosylase-based base editors (gBEs) to broaden the editing scope is highly desirable for biomedical research and agricultural applications. However, the off-target effects and applicability of gBEs need further investigation. We employ GOTI to detect rare DNA off-target events in mouse embryos injected with N-methylpurine glycosylase-based AYBE and gGBE. Transcriptome-wide RNA analysis reveals that TadA8e-V106W, derived from AYBE, induces low-frequency RNA off-target editing. Both base editors efficiently induce A/G-to-Y editing in mouse and sheep embryos, and in newborn lambs. The robust efficiency and specificity of AYBE and gGBE underscore their potential for clinical applications and genetic improvement in livestock.

Background: Transposable elements (TEs) represent a threat to genome integrity due to their proliferative capacity. Eukaryotic cells silence TEs through different molecular mechanisms, including the deposition of repressive histone marks. Previous studies have shown that TE repressive marks can spread to neighboring sequences. However, evidence for this spreading leading to nearby gene silencing remains limited. Similarly, whether TEs induce changes in the enrichment of active histone marks genome-wide, and the potential impact on gene expression have not been widely studied.

Results: In this work, we perform a comprehensive study of the epigenetic effects of 2235 TEs and their potential effects on nearby gene expression on Drosophila melanogaster head, gut, and ovary. While most TEs (816) induce the enrichment of the H3K9me3 repressive mark, with stronger epigenetic effects in the ovary, a substantial number (345 TEs) induce the enrichment of the H3K27ac active mark, particularly in the gut. We find that 70% of the H3K9me3 enriched TEs associated with expression changes downregulate the nearby gene, and 50% of the H3K27ac enriched TEs associated with expression changes lead to gene upregulation. These changes in expression affect specific regulatory networks only in the head. Furthermore, TE epigenetic effects on gene expression are genomic context dependent. Finally, we find that 221 TEs also affect gene expression by disrupting regions enriched for histone marks.  CONCLUSIONS: Overall, our results show that TEs contribute to the generation of regulatory novelty through epigenetic changes, with these epigenetic effects not restricted to gene silencing and being genomic context dependent.

Background: Recent ancient DNA studies uncovering large-scale demographic events in Iberia have presented very limited data for Portugal, a country located at the westernmost edge of continental Eurasia. Here, we present the most comprehensive collection of Portuguese ancient genome-wide data, from 67 individuals spanning 5000 years of human history, from the Neolithic to the nineteenth century.

Results: We identify early admixture between local hunter-gatherers and Anatolian-related farmers in Neolithic Portugal, with a northeastern-southwestern gradient of increasing Magdalenian-associated ancestry persistence in Iberia. This profile continues into the Chalcolithic, though Bell Beaker-associated sites reveal Portugal's first evidence of Steppe-related ancestry. Such ancestry has a broader demographic impact during the Bronze Age, despite continuity of local Chalcolithic genetic ancestry and limited Mediterranean connections. The village of Idanha-a-Velha emerges in the Roman period as a site of significant migration and interaction, presenting a notably diverse genetic profile that includes North African and Eastern Mediterranean ancestries. The Early Medieval period is marked by the arrival of Central European genetic diversity, likely linked to migrations of Germanic tribes, adding to coeval local, African, and Mediterranean influences. The Islamic and Christian Conquest periods show strong genetic continuity in northern Portugal and significant additional African admixture in the south. The latter remains stable during the post-Islamic period, suggesting enduring African influences.

Conclusions: We reveal dynamic patterns of migration in line with cultural exchange across millennia, but also the persistence of local ancestries. Our findings integrate genetic information with historical and archeological data, enhancing our understanding of Iberia's biological and cultural heritage.

Species from diverse animal lineages have conserved groups of orthologous genes together on the same chromosome for over half a billion years since the last common ancestor of bilaterians. Although notable exceptions exist, the stability of chromosome-scale gene linkages has been proposed to be the norm among animals. Here we test this hypothesis across species from 52 bilaterian classes representing 15 different phyla. Contrary to expectations, we find that cases of genome structure conservation are rare, taxonomically restricted and unrepresentative of the general state of bilaterian genomes. Genome restructuring correlates with increased rates of protein sequence evolution and may be an underappreciated factor driving animal adaptation and diversification.