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We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome—composed of approximately one billion base pairs of sequence and an estimated 20,000–23,000 genes—provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.

Transposable elements are parasitic DNAs that can duplicate themselves and jump around their host genomes. They can both disrupt gene function and drive genome evolution. Elbarbary et al. review the roles of two classes of transposable elements in gene regulation and disease: long interspersed elements (LINEs) and short interspersed elements (SINEs). Roughly a third of the human genome consists of LINEs and SINEs. They contribute to a broad range of important genome and gene regulatory features, while at the same time being responsible for number of human diseases. Science , this issue p. 10.1126/science.aac7247 Transposable elements (TEs) are both a boon and a bane to eukaryotic organisms, depending on where they integrate into the genome and how their sequences function once integrated. We focus on two types of TEs: long interspersed elements (LINEs) and short interspersed elements (SINEs). LINEs and SINEs are retrotransposons; that is, they transpose via an RNA intermediate. We discuss how LINEs and SINEs have expanded in eukaryotic genomes and contribute to genome evolution. An emerging body of evidence indicates that LINEs and SINEs function to regulate gene expression by affecting chromatin structure, gene transcription, pre-mRNA processing, or aspects of mRNA metabolism. We also describe how adenosine-to-inosine editing influences SINE function and how ongoing retrotransposition is countered by the body’s defense mechanisms.

Whole-genome synthesis provides a powerful approach for understanding and expanding organism function 1 – 3 . To build large genomes rapidly, scalably and in parallel, we need (1) methods for assembling megabases of DNA from shorter precursors and (2) strategies for rapidly and scalably replacing the genomic DNA of organisms with synthetic DNA. Here we develop bacterial artificial chromosome (BAC) stepwise insertion synthesis (BASIS)—a method for megabase-scale assembly of DNA in Escherichia coli episomes. We used BASIS to assemble 1.1 Mb of human DNA containing numerous exons, introns, repetitive sequences, G-quadruplexes, and long and short interspersed nuclear elements (LINEs and SINEs). BASIS provides a powerful platform for building synthetic genomes for diverse organisms. We also developed continuous genome synthesis (CGS)—a method for continuously replacing sequential 100 kb stretches of the E. coli genome with synthetic DNA; CGS minimizes crossovers 1 , 4 between the synthetic DNA and the genome such that the output for each 100 kb replacement provides, without sequencing, the input for the next 100 kb replacement. Using CGS, we synthesized a 0.5 Mb section of the E. coli genome—a key intermediate in its total synthesis 1 —from five episomes in 10  days. By parallelizing CGS and combining it with rapid oligonucleotide synthesis and episome assembly 5 , 6 , along with rapid methods for compiling a single genome from strains bearing distinct synthetic genome sections 1 , 7 , 8 , we anticipate that it will be possible to synthesize entire E. coli genomes from functional designs in less than 2 months. BAC stepwise insertion synthesis (BASIS) can be used to build synthetic genomes for diverse organisms, and continuous genome synthesis (CGS) enables the rapid synthesis of entire Escherichia coli genomes from functional designs.

Abstract Rationale Prenatal exposure to tobacco smoke increases the risk for diseases later in the child's life that may be mediated through alterations in DNA methylation. Objectives To demonstrate that differences in DNA methylation patterns occur in children exposed to tobacco smoke and that variation in detoxification genes may alter these associations. Methods Methylation of DNA repetitive elements, LINE1 and AluYb8, was measured using bisulfite conversion and pyrosequencing in buccal cells of 348 children participating in the Children's Health Study. Gene-specific CpG methylation differences associated with smoke exposure were screened in 272 participants in the Children's Health Study children using an Illumina GoldenGate panel. CpG loci that demonstrated a statistically significant difference in methylation were validated by pyrosequencing. Estimates were standardized across loci using a Z score to enable cross-comparison of results. Measurements and Main Results DNA methylation patterns were associated with in utero exposure to maternal smoking. Exposed children had significantly lower methylation of AluYb8 (β, −0.31; P = 0.03). Differences in smoking-related effects on LINE1 methylation were observed in children with the common GSTM1 null genotype. Differential methylation of CpG loci in eight genes was identified through the screen. Two genes, AXL and PTPRO, were validated by pyrosequencing and showed significant increases in methylation of 0.37 (P = 0.005) and 0.34 (P = 0.02) in exposed children. The associations with maternal smoking varied by a common GSTP1 haplotype. Conclusions Life-long effects of in utero exposures may be mediated through alterations in DNA methylation. Variants in detoxification genes may modulate the effects of in utero exposure through epigenetic mechanisms.

In sexually reproducing organisms, life begins with the fusion of transcriptionally silent gametes, the oocyte and sperm. Although initiation of transcription in the embryo, known as zygotic genome activation (ZGA), is universally required for development, the transcription factors regulating this process are poorly conserved. In this Perspective, we discuss recent insights into the mechanisms of ZGA in totipotent mammalian embryos, namely ZGA regulation by several transcription factors, including by orphan nuclear receptors (OrphNRs) such as the pioneer transcription factor NR5A2, and by factors of the DUX, TPRX and OBOX families. We performed a meta-analysis and compiled a list of pan-ZGA genes, and found that most of these genes are indeed targets of the above transcription factors. Remarkably, more than a third of these ZGA genes appear to be regulated both by OrphNRs such as NR5A2 and by OBOX proteins, whose motifs co-occur in SINE B1 retrotransposable elements, which are enriched near ZGA genes. We propose that ZGA in mice is activated by recruitment of multiple transcription factors to SINE B1 elements that function as enhancers, and discuss a potential relevance of this mechanism to Alu retrotransposable elements in human ZGA. Although zygotic genome activation (ZGA) is universally required for development, the responsible transcription factors are poorly conserved. In mammalian totipotent embryos, (pioneer) transcription factors of two families co-regulate many ZGA genes by binding to nearby SINE retrotransposons, which thus function as their enhancers.

Background: The African hedgehog (Atelerix albiventris) exhibits specialized skin differentiation leading to spine formation, yet its regulatory mechanisms remain unclear. Transposable elements (TEs), particularly LINEs (long interspersed nuclear elements) and SINEs (short interspersed nuclear elements), are known to influence genome organization and gene regulation. Objectives: Given the high proportion of SINEs in the hedgehog genome, this study aims to characterize the distribution, evolutionary dynamics, and potential regulatory roles of LINEs and SINEs, focusing on their associations with chromatin architecture, DNA methylation, and gene expression. Methods: We analyzed LINE and SINE distribution using HiFi sequencing and classified TE families through phylogenetic reconstruction. Hi-C data were used to explore TE interactions with chromatin architecture, while whole-genome 5mCpG methylation was inferred from PacBio HiFi reads of muscle tissue using a deep-learning-based approach. RNA-seq data from skin tissues were analyzed to assess TE expression and potential associations with genes linked to spine development. Results: SINEs form distinct genomic blocks in GC-rich and highly methylated regions, whereas LINEs are enriched in AT-rich, hypomethylated regions. LINEs and SINEs are associated differently with A/B compartments, with SINEs in euchromatin and LINEs in heterochromatin. Methylation analysis suggests that younger TEs tend to have higher methylation levels, and expression analysis indicates that some differentially expressed TEs may be linked to genes involved in epidermal and skeletal development. Conclusions: This study provides a genome-wide perspective on LINE and SINE distribution, methylation patterns, and potential regulatory roles in A. albiventris. While not establishing a direct causal link, the findings suggest that TEs may influence gene expression associated with spine development, offering a basis for future functional studies.

Background Short interspersed elements (SINEs) are non-autonomous retroelements that are transcribed by RNA polymerase III from an internal promoter. Most SINE families originate from tRNAs, but a few, exclusively within supraprimates (primates, rodents, tree shrews) and, exceptionally, hagfish, derive from the 7SL RNA. These 7SL-derived SINEs all arose after an ~ 183-nt central deletion in the 7SL RNA sequence and are mobilized by LINE1-encoded reverse transcriptase. No 7SL-derived SINE has previously been reported outside these taxa. Results Mining of mole (Talpidae) genomes revealed no mole-specific tRNA-derived SINE in the gracile shrew mole Uropsilus gracilis . Instead, ~ 280 000 copies of a dimeric 7SL RNA-derived SINE, named Urop, populate its genome but not five other talpid species. Three subfamilies (a–c) share two 7SL-derived monomers joined by an A-rich linker. The left monomer and Urop_a right monomer carry the canonical central deletion; Urop_b/c right monomers additionally harbor a 24-nt tandem duplication, paralleling the 29-nt quasi-dimer of murid B1. Monomeric fossils suggest they preceded dimeric Urop formation. Sequence divergence and subfamily analysis date the origin of Urop soon after the Uropsilinae split from other moles. Urop_c, the youngest subfamily, displays a striking excess of extra-long pure poly(A) tails, far exceeding those in young human AluY elements. Conclusions Urop represents a remarkable case of convergent evolution, independently generating an Alu-like dimeric SINE in a distantly related mammal. Its independent origin from 7SL RNA, parallel structural trajectory (monomer → dimer via identical deletion boundaries), and suppression of tRNA-derived SINEs mirror the evolutionary history of primate Alu. The abundance of long intact poly(A) tails in Urop_c suggests unique biochemical controls on tail dynamics and hint at continued retropositional activity. These findings underscore the exceptional evolutionary potential of rare, large-scale deletions within 7SL RNA as a SINE progenitor and raises new questions about poly(A) tail regulation and SINE family dynamics.

SVA (SINE (short interspersed nuclear element)–VNTR (variable number of tandem repeats)– Alu ) retrotransposons remain active in humans and contribute to individual genetic variation. Polymorphic SVA alleles harbor gene regulatory potential and can cause genetic disease. However, how SVA insertions are controlled and functionally impact human disease is unknown. Here we dissect the epigenetic regulation and influence of SVAs in cellular models of X-linked dystonia parkinsonism (XDP), a neurodegenerative disorder caused by an SVA insertion at the TAF1 locus. We demonstrate that the KRAB zinc finger protein ZNF91 establishes H3K9me3 and DNA methylation over SVAs, including polymorphic alleles, in human neural progenitor cells. The resulting mini-heterochromatin domains attenuate the cis -regulatory impact of SVAs. This is critical for XDP pathology; removal of local heterochromatin severely aggravates the XDP molecular phenotype, resulting in increased TAF1 intron retention and reduced expression. Our results provide unique mechanistic insights into how human polymorphic transposon insertions are recognized and how their regulatory impact is constrained by an innate epigenetic defense system. Here the authors elucidate how epigenetic regulation influences the regulatory impact of transposable elements in the human genome using cellular models of the neurodegenerative disease XDP, which is caused by an SVA insertion at the TAF1 locus.

SINE-VNTR- Alu (SVA) retrotransposons are transposable elements which represent a source of genetic variation. We previously demonstrated that the presence/absence of a human-specific SVA, termed SVA_67, correlated with the progression of Parkinson’s disease (PD). In the present study, we demonstrate that SVA_67 acts as expression quantitative trait loci, thereby exhibiting a strong regulatory effect across the genome using whole genome and transcriptomic data from the Parkinson’s progression markers initiative cohort. We further show that SVA_67 is polymorphic for its variable number tandem repeat domain which correlates with both regulatory properties in a luciferase reporter gene assay in vitro and differential expression of multiple genes in vivo. Additionally, this variation’s utility as a biomarker is reflected in a correlation with a number of PD progression markers. These experiments highlight the plethora of transcriptomic and phenotypic changes associated with SVA_67 polymorphism which should be considered when investigating the missing heritability of neurodegenerative diseases.

Recent comprehensive sequence analysis of the maize genome now permits detailed discovery and description of all transposable elements (TEs) in this complex nuclear environment. Reiteratively optimized structural and homology criteria were used in the computer-assisted search for retroelements, TEs that transpose by reverse transcription of an RNA intermediate, with the final results verified by manual inspection. Retroelements were found to occupy the majority (>75%) of the nuclear genome in maize inbred B73. Unprecedented genetic diversity was discovered in the long terminal repeat (LTR) retrotransposon class of retroelements, with >400 families (>350 newly discovered) contributing >31,000 intact elements. The two other classes of retroelements, SINEs (four families) and LINEs (at least 30 families), were observed to contribute 1,991 and approximately 35,000 copies, respectively, or a combined approximately 1% of the B73 nuclear genome. With regard to fully intact elements, median copy numbers for all retroelement families in maize was 2 because >250 LTR retrotransposon families contained only one or two intact members that could be detected in the B73 draft sequence. The majority, perhaps all, of the investigated retroelement families exhibited non-random dispersal across the maize genome, with LINEs, SINEs, and many low-copy-number LTR retrotransposons exhibiting a bias for accumulation in gene-rich regions. In contrast, most (but not all) medium- and high-copy-number LTR retrotransposons were found to preferentially accumulate in gene-poor regions like pericentromeric heterochromatin, while a few high-copy-number families exhibited the opposite bias. Regions of the genome with the highest LTR retrotransposon density contained the lowest LTR retrotransposon diversity. These results indicate that the maize genome provides a great number of different niches for the survival and procreation of a great variety of retroelements that have evolved to differentially occupy and exploit this genomic diversity.