Genome Expansion Research Articles

Metamorphosis Imposes Variable Constraints on Genome Expansion through Effects on Development.

Genome size varies ∼100,000-fold across eukaryotes and has long been hypothesized to be influenced by metamorphosis in animals. Transposable element accumulation has been identified as a major driver of increase, but the nature of constraints limiting the size of genomes has remained unclear, even as traits such as cell size and rate of development co-vary strongly with genome size. Salamanders, which possess diverse metamorphic and non-metamorphic life histories, join the lungfish in having the largest vertebrate genomes-3 to 40 times that of humans-as well as the largest range of variation in genome size. We tested 13 biologically-inspired hypotheses exploring how the form of metamorphosis imposes varying constraints on genome expansion in a broadly representative phylogeny containing 118 species of salamanders. We show that metamorphosis during which animals undergo the most extensive and synchronous remodeling imposes the most severe constraint against genome expansion, with the severity of constraint decreasing with reduced extent and synchronicity of remodeling. More generally, our work demonstrates the potential for broader interpretation of phylogenetic comparative analysis in exploring the balance of multiple evolutionary pressures shaping phenotypic evolution.

Identification and Characterization of ZF-HD Genes in Response to Abscisic Acid and Abiotic Stresses in Maize

The zinc finger homeodomain (ZF-HD) genes belong to the homeobox gene family, playing critical roles in flower development and stress response. Despite their importance, however, to date there has been no genome-wide identification and characterization of the ZF-HD genes that are probably involved in stress responses in maize. In this study, 24 ZF-HD genes were identified, and their chromosomal locations, protein properties, duplication patterns, structures, conserved motifs and expression patterns were investigated. The results revealed that the ZF-HD genes are unevenly distributed on nine chromosomes and that most of these genes lack introns. Six and two ZF-HD genes have undergone segmental and tandem duplication, respectively, during genome expansion. These 24 ZF-HD transcription factors were classified into six major groups on the basis of protein molecular evolutionary relationship. The expression profiles of these genes in different tissues were evaluated, resulting in producing two distinct clusters. ZF-HD genes are preferentially expressed in reproductive tissues. Furthermore, expression profiles of the 24 ZF-HD genes in response to different kinds of stresses revealed that ten genes were simultaneously up-regulated under ABA, salt and PEG treatments; meanwhile four genes were simultaneously down-regulated. These findings will pave the way for deciphering the function and mechanism of ZF-HD genes on how to implicate in abiotic stress.

PlanTEnrichment: A How-to Guide on Rapid Identification of Transposable Elements Associated with Regions of Interest in Select Plant Genomes.

Transposable elements (TEs) are repeat elements that can relocate or create novel copies of themselves in the genome and contribute to genomic complexity and expansion, via events such as chromosome recombination or regulation of gene expression. However, given the large number of such repeats across the genome, identifying repeats of interest can be a challenge in even well-annotated genomes, especially in more complex, TE-rich plant genomes. Here, we describe a protocol for PlanTEnrichment, a database we created comprising information on 11 plant genomes to analyze stress-associated TEs using publicly available data. By selecting a genome and providing a list of genes or genomic regions whose TE associations the user wants to identify, the user can rapidly obtain TE subfamilies found near the provided regions, as well as their superfamily and class, and the enrichment values of the repeats. The results also provide the locations of individual repeat instances found, alongside the input regions or genes they are associated with, and a bar graph of the top ten most significant repeat subfamilies identified. PlanTEnrichment is freely available at http://tools.ibg.deu.edu.tr/plantenrichment/ and can be used by researchers with rudimentary or no proficiency in computational analysis of TE elements, allowing for expedience in the identification of TEs of interest and helping further our understanding of the potential contributions of TEs in plant genomes.

Larger genomes show improved buffering of adult fitness against environmental stress in seed beetles.

Our general understanding of the evolution of genome size (GS) is incomplete, and it has long been clear that GS does not reflect organismal complexity. Here, we assess the hypothesis that larger genomes may allow organisms to better cope with environmental variation. It is, for example, possible that genome expansion due to proliferation of transposable elements or gene duplications may affect the ability to regulate and fine-tune transcriptional profiles. We used 18 populations of the seed beetle Callosobruchus maculatus, which differ in GS by up to 4.5%, and exposed adults and juveniles to environmental stress in a series of experiments where stage-specific fitness was assayed. We found that populations with larger genomes were indeed better buffered against environmental stress for adult, but not for juvenile, fitness. The genetic correlation across populations between GS and canalization of adult fitness is consistent with a role for natural selection in the evolution of GS.

Genome assembly of Musa beccarii shows extensive chromosomal rearrangements and genome expansion during evolution of Musaceae genomes.

Musa beccarii (Musaceae) is a banana species native to Borneo, sometimes grown as an ornamental plant. The basic chromosome number of Musa species is x = 7, 10, or 11; however, M. beccarii has a basic chromosome number of x = 9 (2n = 2x = 18), which is the same basic chromosome number of species in the sister genera Ensete and Musella. Musa beccarii is in the section Callimusa, which is sister to the section Musa. We generated a high-quality chromosome-scale genome assembly of M. beccarii to better understand the evolution and diversity of genomes within the family Musaceae. The M. beccarii genome was assembled by long-read and Hi-C sequencing, and genes were annotated using both long Iso-seq and short RNA-seq reads. The size of M. beccarii was the largest among all known Musaceae assemblies (∼570 Mbp) due to the expansion of transposable elements and increased 45S ribosomal DNA sites. By synteny analysis, we detected extensive genome-wide chromosome fusions and fissions between M. beccarii and the other Musa and Ensete species, far beyond those expected from differences in chromosome number. Within Musaceae, M. beccarii showed a reduced number of terpenoid synthase genes, which are related to chemical defense, and enrichment in lipid metabolism genes linked to the physical defense of the cell wall. Furthermore, type III polyketide synthase was the most abundant biosynthetic gene cluster (BGC) in M. beccarii. BGCs were not conserved in Musaceae genomes. The genome assembly of M. beccarii is the first chromosome-scale genome assembly in the Callimusa section in Musa, which provides an important genetic resource that aids our understanding of the evolution of Musaceae genomes and enhances our knowledge of the pangenome.

Genome size does not influence extinction risk in the world's amphibians

AbstractVariation in genome size spans multiple orders of magnitude among animals. Despite the longstanding debate regarding the adaptive value or costs of genomic complexity, genome size has been proposed to influence extinction risk under the rapidly changing environments of the Anthropocene.The main hypothesis suggests that genome enlargement increases the accumulation of deleterious mutations while reducing rates of organismal growth and development. These combined effects of larger genome size are predicted to trigger population declines that can lead to extinction, especially under rapidly changing environments that disrupt demographic resilience.Comparative evidence from terrestrial plants and across vertebrates has provided mixed support for this hypothesis. However, large‐scale comparative studies based on explicit phylogenetic approaches remain lacking. Using a global‐scale amphibian dataset and two recognised proxies of extinction risk (International Union for Conservation of Nature IUCN conservation categories and population trends), we test the prediction that genomes are larger (as estimated by C‐value) in species facing extinction risk. We combine these analyses with life‐history traits widely known to be implicated with extinctions (body size, fecundity), along with a range of environmental factors.Our phylogenetic analyses consistently failed to identify an effect of genome size on either of the two proxies for extinction risk. The only consistent predictor of extinction risk observed across models performed for amphibians combined and for orders separately was decreasing geographical range size. We also identified a role for larger body size, decreasing range of environmental temperature (for anurans) and increasing levels of UV‐B radiation (for salamanders) as drivers of increasing threat.Our study provides no support for the prediction that species with larger genomes suffer heightened risk of extinction. We discuss some fundamental limitations underlying the genome size‐extinction hypothesis, and suggest that it is not a promising avenue to elucidate the causes of biodiversity declines in the Anthropocene.Read the freePlain Language Summaryfor this article on the Journal blog.

Expanded‐repeat‐RNA‐mediated disease mechanisms in myotonic dystrophy

AbstractMyotonic dystrophy (DM) is the most common muscular dystrophy in adults, affecting skeletal muscle as well as cardiac and smooth muscle. Furthermore, involvement of the central nervous system, endocrine organs, and eyes is often seen, with debilitating consequences. The condition is an autosomal‐dominant inherited genetic disease caused by abnormal genomic expansion of tandem repeats. Myotonic dystrophy type 1 (DM1) results from expansion of a CTG repeat in the 3′‐untranslated region of the gene encoding dystrophia myotonica‐protein kinase (DMPK), whereas myotonic dystrophy type 2 (DM2) is caused by expansion of a CCTG repeat in the first intron of the gene encoding CCHC‐type zinc finger nucleic acid‐binding protein (CNBP). Both types of DM exhibit abnormal mRNA transcribed from the mutated gene containing expanded repeats, which exert toxic gain‐of‐function effects on various proteins involved in cellular processes such as alternative splicing, signaling pathways, and cellular senescence. The present review discusses the expanded‐repeat‐RNA‐mediated molecular pathomechanisms in DM.

The associated evolution among the extensive RNA editing, GC‐biased mutation, and PPR family expansion in the organelle genomes of Selaginellaceae

AbstractExtensive C‐to‐U editing has been reported from plastid genomes (plastomes) and mitochondrial genomes (mitogenomes) of spikemoss. While “reverse” U‐to‐C editing was recorded in other seed‐free plants such as hornworts, quillworts, and ferns, it was not observed in spikemosses. However, no comprehensive study on the association between RNA editing and other genomic features was conducted for the organelle genomes of spikemosses. Here, we report thousands of C‐to‐U editing sites from plastomes and mitogenomes of two species: 1767 and 2394 edits in Selaginella remotifolia, and 4091 and 2786 edits in Selaginella nipponica, respectively. Comparative analyses revealed two different editing frequencies among plastomes, but one similar frequency in mitogenomes. The different editing frequency in the Selaginella organelle genomes is related to the nonsynonymous substitution rate and the genome structural complexity. The high guanine and cytosine (GC) content caused by GC‐biased mutations in organelle genomes might be related to the absence of U‐to‐C editing in Selaginellaceae. Using RNA‐seq and whole‐genome data, we screened the pentatricopeptide repeat (PPR) family and discovered that the number of aspartic acid–tyrosine–tryptophan (DYW) domain‐containing PPR proteins corresponded roughly to the editing abundance in the Selaginella organelle genomes. Consequently, we hypothesize that associated evolution among RNA editing, GC‐biased mutation in organelle genomes, and the PPR protein family encoded in the nuclear genome, is probably triggered by the aberrant DNA repair system in Selaginellaceae. Our study provides new insights into the association between organelle and nuclear genomes in Selaginellaceae, which would contribute to understanding the evolution of post‐transcriptional modifications of organelle genomes in land plants.

Characterization of the Dicranostigma leptopodum chloroplast genome and comparative analysis within subfamily Papaveroideae

BackgroundDicranostigma leptopodum (Maxim.) Fedde is a perennial herb with bright yellow flowers, well known as "Hongmao Cao" for its medicinal properties, and is an excellent early spring flower used in urban greening. However, its molecular genomic information remains largely unknown. Here, we sequenced and analyzed the chloroplast genome of D. leptopodum to discover its genome structure, organization, and phylogenomic position within the subfamily Papaveroideae.ResultsThe chloroplast genome size of D. leptopodum was 162,942 bp, and D. leptopodum exhibited a characteristic circular quadripartite structure, with a large single-copy (LSC) region (87,565 bp), a small single-copy (SSC) region (18,759 bp) and a pair of inverted repeat (IR) regions (28,309 bp). The D. leptopodum chloroplast genome encoded 113 genes, including 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. The dynamics of the genome structures, genes, IR contraction and expansion, long repeats, and single sequence repeats exhibited similarities, with slight differences observed among the eight Papaveroideae species. In addition, seven interspace regions and three coding genes displayed highly variable divergence, signifying their potential to serve as molecular markers for phylogenetic and species identification studies. Molecular evolution analyses indicated that most of the genes were undergoing purifying selection. Phylogenetic analyses revealed that D. leptopodum formed a clade with the tribe Chelidonieae.ConclusionsOur study provides detailed information on the D. leptopodum chloroplast genome, expanding the available genomic resources that may be used for future evolution and genetic diversity studies.

Chromosome-level genome assembly of the European flat oyster (Ostrea edulis) provides insights into its evolution and adaptation

The European flat oyster (Ostrea edulis) is an endangered and economically important marine bivalve species that plays a critical role in the coastal ecosystem. Here, we report a high-quality chromosome-level genome assembly of O. edulis, generated using PacBio HiFi-CCS long reads and annotated with Nanopore full-length transcriptome. The O. edulis genome covers 946.06 Mb (scaffold N50 94.82 Mb) containing 34,495 protein-coding genes and a high proportion of repeat sequences (58.49 %). The reconstructed demographic histories show that O. edulis population might be shaped by breeding habit (embryo brooding) and historical climatic change. Comparative genomic analysis indicates that transposable elements may drive lineage-specific evolution in oysters. Notably, the O. edulis genome has a Hox gene cluster rearrangement that has never been reported in bivalves, making this species valuable for evolutionary studies of molluscan diversification. Moreover, genome expansion of O. edulis is probably central to its adaptation to filter-feeding and sessile lifestyles, as well as embryo brooding and pathogen resistance, in coastal ecosystems. This chromosome-level genome assembly provides new insights into the genome feature of oysters, and presents an important resource for genetic research, evolutionary studies, and biological conservation of O. edulis.

TDP-43 safeguards the embryo genome from L1 retrotransposition.

Transposable elements (TEs) are genomic parasites that propagate within the host genome and introduce mutations. Long interspersed nuclear element-1 (LINE-1 or L1) is the major TE class, which occupies nearly 20% of the mouse genome. L1 is highly active in mammalian preimplantation embryos, posing a major threat to genome integrity, but the mechanism of stage-specific protection against L1 retrotransposition is unknown. Here, we show that TAR DNA-binding protein 43 (TDP-43), mutations in which constitute a major risk factor for amyotrophic lateral sclerosis, inhibits L1 retrotransposition in mouse embryonic stem cells (mESCs) and preimplantation embryos. Knockdown of TDP-43 resulted in massive genomic L1 expansion and impaired cell growth in preimplantation embryos and ESCs. Functional analysis demonstrated that TDP-43 interacts with L1 open reading frame 1 protein (L1 ORF1p) to mediate genomic protection, and loss of this interaction led to derepression of L1 retrotransposition. Our results identify TDP-43 as a guardian of the embryonic genome.

The compact genome of Caenorhabditis niphades n. sp., isolated from a wood-boring weevil, Niphades variegatus

BackgroundThe first metazoan genome sequenced, that of Caenorhabditis elegans, has motivated animal genome evolution studies. To date > 50 species from the genus Caenorhabditis have been sequenced, allowing research on genome variation.ResultsIn the present study, we describe a new gonochoristic species, Caenorhabditis niphades n. sp., previously referred as C. sp. 36, isolated from adult weevils (Niphades variegatus), with whom they appear to be tightly associated during its life cycle. Along with a species description, we sequenced the genome of C. niphades n. sp. and produced a chromosome-level assembly. A genome comparison highlighted that C. niphades n. sp. has the smallest genome (59 Mbp) so far sequenced in the Elegans supergroup, despite being closely related to a species with an exceptionally large genome, C. japonica.ConclusionsThe compact genome of C. niphades n. sp. can serve as a key resource for comparative evolutionary studies of genome and gene number expansions in Caenorhabditis species.

Expansion of viral genomes with viral protein genome linked copies

Virus protein-linked genome (VPg) proteins are required for replication. VPgs are duplicated in a subset of RNA viruses however their roles are not fully understood and the extent of viral genomes containing VPg copies has not been investigated in detail. Here, we generated a novel bioinformatics approach to identify VPg sequences in viral genomes using hidden Markov models (HMM) based on alignments of dicistrovirus VPg sequences. From metagenomic datasets of dicistrovirus genomes, we identified 717 dicistrovirus genomes containing VPgs ranging from a single copy to 8 tandem copies. The VPgs are classified into nine distinct types based on their sequence and length. The VPg types but not VPg numbers per viral genome followed specific virus clades, thus suggesting VPgs co-evolved with viral genomes. We also identified VPg duplications in aquamavirus and mosavirus genomes. This study greatly expands the number of viral genomes that contain VPg copies and indicates that duplicated viral sequences are more widespread than anticipated.

Chromosome-level genome assembly of bunching onion illuminates genome evolution and flavor formation in Allium crops

The Allium genus is cultivated globally as vegetables, condiments, or medicinal plants and is characterized by large genomes and strong pungency. However, the genome evolution and genomic basis underlying their unique flavor formation remain poorly understood. Herein, we report an 11.27-Gb chromosome-scale genome assembly for bunching onion (A. fistulosum). The uneven bursts of long-terminal repeats contribute to diversity in genome constituents, and dispersed duplication events largely account for gene expansion in Allium genomes. The extensive duplication and differentiation of alliinase and lachrymatory factor synthase manifest as important evolutionary events during flavor formation in Allium crops. Furthermore, differential selective preference for flavor-related genes likely lead to the variations in isoalliin content in bunching onions. Moreover, we reveal that China is the origin and domestication center for bunching onions. Our findings provide insights into Allium genome evolution, flavor formation and domestication history and enable future genome-assisted breeding of important traits in these crops.

Evolution of mitogen-activated protein kinase family and their immune function in Apostichopus japonicus

The mitogen-activated protein kinase family plays an important role in cell differentiation, growth, proliferation, and survival. However, the current research on the mitogen-activated protein kinase (MAPK) family in invertebrates is limited to the individual gene, and the analysis has not been conducted at the family level. In the present study, echinoderm MAPK family was identified by genomic screening, and five members, including three ERK subfamily members, one c-Jun N-terminal kinase (JNK) subfamily, and one p38-MAPK member were detected. Phylogenetic analysis showed that three MAPK subfamilies were separated into three separated clusters, and ERK subfamily appeared earlier than the other two subfamilies. Synteny analysis revealed that the p38 subfamily might be derived from the continuous gene duplication events of MAPK14 subfamily in invertebrates, which displayed genome expansion via gene duplication in vertebrates. The role of MAPK family in echinoderm immune defense was determined by investigating the expression profiles of MAPKs in Vibrio splendidus-challenged Apostichopus japonicus and LPS-exposed coelomocytes. The result showed that five MAPK members displayed induced expression profiles both in vitro and in vivo, and the peak expression was detected at different time points. Our study provides new insights into the evolutionary history of the MAPK family and show the similar immune function among MAPK members.

Pan-genome evolution and its association with divergence of metabolic functions in Bifidobacterium genus.

Previous studies were mainly focused on genomic evolution and diversity of type species of Bifidobacterium genus due to their health-promoting effect on host. However, those studies were mainly based on species-level taxonomic resolution, adaptation, and characterization of carbohydrate metabolic features of the bifidobacterial species. Here, a comprehensive analysis of the type strain genome unveils the association of pan-genome evolution with the divergence of metabolic function of the Bifidobacterium genus. This study has also demonstrated that horizontal gene transfer, as well as genome expansion and reduction events, leads to the divergence of metabolic functions in Bifidobacterium genus. Furthermore, the genome-based search of probiotic traits among all the available bifidobacterial type strains gives hints on type species, that could confer health benefits to nutrient-deficient individuals. Altogether, the present study provides insight into the developments of genomic evolution, functional divergence, and potential probiotic type species of the Bifidobacterium genus.

The plastomes of Hyalomonas oviformis and Hyalogonium fusiforme evolved dissimilar architectures after the loss of photosynthesis.

The loss of photosynthesis in land plants and algae is typically associated with parasitism but can also occur in free‐living species, including chlamydomonadalean green algae. The plastid genomes (ptDNAs) of colorless chlamydomonadaleans are surprisingly diverse in architecture, including highly expanded forms ( Polytoma uvella and Leontynka pallida) as well as outright genome loss (Polytomella species). Here, we explore the ptDNAs of Hyalomonas (Hm.) oviformis (SAG 62‐27; formerly known as Polytoma oviforme) and Hyalogonium (Hg.) fusiforme (SAG 62‐1c), each representing independent losses of photosynthesis within the Chlamydophyceae. The Hm. oviformis ptDNA is moderately sized (132 kb) with a reduced gene complement (but still encoding the ATPase subunits) and is in fact smaller than that of its photosynthetic relative Hyalomonas chlamydogama SAG 11‐48b (198.3 kb). The Hg. fusiforme plastome, however, is the largest yet observed in nonphotosynthetic plants or algae (~463 kb) and has a coding repertoire that is almost identical to that of its photosynthetic relatives in the genus Chlorogonium. Furthermore, the ptDNA of Hg. fusiforme shows no clear evidence of pseudogenization, which is consistent with our analyses showing that Hg. fusiforme is the nonphotosynthetic lineage of most recent origin among known colorless Chlamydophyceae. Together, these new ptDNAs clearly show that, in contrast to parasitic algae, plastid genome compaction is not an obligatory route following the loss of photosynthesis in free‐living algae, and that certain chlamydomonadalean algae have a remarkable propensity for genomic expansion, which can persist regardless of the trophic strategy.

In-depth analysis of genomes and functional genomics of orchid using cutting-edge high-throughput sequencing.

High-throughput sequencing technology has been facilitated the development of new methodologies and approaches for studying the origin and evolution of plant genomes and subgenomes, population domestication, and functional genomics. Orchids have tens of thousands of members in nature. Many of them have promising application potential in the extension and conservation of the ecological chain, the horticultural use of ornamental blossoms, and the utilization of botanical medicines. However, a large-scale gene knockout mutant library and a sophisticated genetic transformation system are still lacking in the improvement of orchid germplasm resources. New gene editing tools, such as the favored CRISPR-Cas9 or some base editors, have not yet been widely applied in orchids. In addition to a large variety of orchid cultivars, the high-precision, high-throughput genome sequencing technology is also required for the mining of trait-related functional genes. Nowadays, the focus of orchid genomics research has been directed to the origin and classification of species, genome evolution and deletion, gene duplication and chromosomal polyploidy, and flower morphogenesis-related regulation. Here, the progressing achieved in orchid molecular biology and genomics over the past few decades have been discussed, including the evolution of genome size and polyploidization. The frequent incorporation of LTR retrotransposons play important role in the expansion and structural variation of the orchid genome. The large-scale gene duplication event of the nuclear genome generated plenty of recently tandem duplicated genes, which drove the evolution and functional divergency of new genes. The evolution and loss of the plastid genome, which mostly affected genes related to photosynthesis and autotrophy, demonstrated that orchids have experienced more separate transitions to heterotrophy than any other terrestrial plant. Moreover, large-scale resequencing provide useful SNP markers for constructing genetic maps, which will facilitate the breeding of novel orchid varieties. The significance of high-throughput sequencing and gene editing technologies in the identification and molecular breeding of the trait-related genes in orchids provides us with a representative trait-improving gene as well as some mechanisms worthy of further investigation. In addition, gene editing has promise for the improvement of orchid genetic transformation and the investigation of gene function. This knowledge may provide a scientific reference and theoretical basis for orchid genome studies.

Molecular diversity and phenotypic pleiotropy of ancient genomic regulatory loci derived from human endogenous retrovirus type H (HERVH) promoter LTR7 and HERVK promoter LTR5_Hs and their contemporary impacts on pathophysiology of Modern Humans

Timelines of population-level effects of viruses on humans varied from the evolutionary scale of million years to contemporary spread of viral infections. Correspondingly, these events are exemplified by: (i) emergence of human endogenous retroviruses (HERVs) from ancient germline infections leading to stable integration of viral genomes into human chromosomes; and (ii) wide-spread viral infections reaching a global pandemic state such as the COVID-19 pandemic. Despite significant efforts, understanding of HERV’s roles in governance of genomic regulatory networks, their impacts on primate evolution and development of human-specific physiological and pathological phenotypic traits remains limited. Remarkably, present analyses revealed that expression of a dominant majority of genes (1696 of 1944 genes; 87%) constituting high-confidence down-steam regulatory targets of defined HERV loci was significantly altered in cells infected with the SARS-CoV-2 coronavirus, a pathogen causing the global COVID-19 pandemic. This study focused on defined sub-sets of DNA sequences derived from HERVs that are expressed at specific stages of human preimplantation embryogenesis and exert regulatory actions essential for self-renewal and pluripotency. Evolutionary histories of LTR7/HERVH and LTR5_Hs/HERVK were charted based on evidence of the earliest presence and expansion of highly conserved (HC) LTR sequences. Sequence conservation analyses of most recent releases 17 primate species’ genomes revealed that LTR7/HERVH have entered germlines of primates in Africa after the separation of the New World Monkey lineage, while LTR5_Hs/HERVK successfully colonized primates’ germlines after the segregation of Gibbons’ species. Subsequently, both LTR7 and LTR5_Hs undergo a marked ~ fourfold–fivefold expansion in genomes of Great Apes. Timelines of quantitative expansion of both LTR7 and LTR5_Hs loci during evolution of Great Apes appear to replicate the consensus evolutionary sequence of increasing cognitive and behavioral complexities of non-human primates, which seems particularly striking for LTR7 loci and 11 distinct LTR7 subfamilies. Consistent with previous reports, identified in this study, 351 human-specific (HS) insertions of LTR7 (175 loci) and LTR5_Hs (176 loci) regulatory sequences have been linked to genes implicated in establishment and maintenance of naïve and primed pluripotent states and preimplantation embryogenesis phenotypes. Unexpectedly, HS-LTRs manifest regulatory connectivity to genes encoding markers of 12 distinct cells’ populations of fetal gonads, as well as genes implicated in physiology and pathology of human spermatogenesis, including Y-linked spermatogenic failure, oligo- and azoospermia. Granular interrogations of genes linked with 11 distinct LTR7 subfamilies revealed that mammalian offspring survival (MOS) genes seem to remain one of consistent regulatory targets throughout ~ 30 MYA of the divergent evolution of LTR7 loci. Differential GSEA of MOS versus non-MOS genes identified clearly discernable dominant enrichment patterns of phenotypic traits affected by MOS genes linked with LTR7 (562 MOS genes) and LTR5_Hs (126 MOS genes) regulatory loci across the large panel of genomics and proteomics databases reflecting a broad spectrum of human physiological and pathological traits. GSEA of LTR7-linked MOS genes identified more than 2200 significantly enriched records of human common and rare diseases and gene signatures of 466 significantly enriched records of Human Phenotype Ontology traits, including Autosomal Dominant (92 genes) and Autosomal Recessive (93 genes) Inheritance. LTR7 regulatory elements appear linked with genes implicated in functional and morphological features of central nervous system, including synaptic transmission and protein–protein interactions at synapses, as well as gene signatures differentially regulated in cells of distinct neurodevelopmental stages and morphologically diverse cell types residing and functioning in human brain. These include Neural Stem/Precursor cells, Radial Glia cells, Bergman Glia cells, Pyramidal cells, Tanycytes, Immature neurons, Interneurons, Trigeminal neurons, GABAergic neurons, and Glutamatergic neurons. GSEA of LTR7-linked genes identified significantly enriched gene sets encoding markers of more than 80 specialized types of neurons and markers of 521 human brain regions, most prominently, subiculum and dentate gyrus. Identification and characterization of 1944 genes comprising high-confidence down-steam regulatory targets of LTR7 and/or LTR5_Hs loci validated and extended these observations by documenting marked enrichments for genes implicated in neoplasm metastasis, intellectual disability, autism, multiple cancer types, Alzheimer’s, schizophrenia, and other brain disorders. Overall, genes representing down-stream regulatory targets of ancient retroviral LTRs exert the apparently cooperative and exceedingly broad phenotypic impacts on human physiology and pathology. This is exemplified by altered expression of 93% high-confidence LTR targets in cells infected by contemporary viruses, revealing a convergence of virus-inflicted aberrations on genomic regulatory circuitry governed by ancient retroviral LTR elements and interference with human cells’ differentiation programs.

Genome Assembly of the Polyclad Flatworm Prostheceraeus crozieri.

Polyclad flatworms are widely thought to be one of the least derived of the flatworm classes and, as such, are well placed to investigate evolutionary and developmental features such as spiral cleavage and larval diversification lost in other platyhelminths. Prostheceraeus crozieri, (formerly Maritigrella crozieri), is an emerging model polyclad flatworm that already has some useful transcriptome data but, to date, no sequenced genome. We have used high molecular weight DNA extraction and long-read PacBio sequencing to assemble the highly repetitive (67.9%) P. crozieri genome (2.07 Gb). We have annotated 43,325 genes, with 89.7% BUSCO completeness. Perhaps reflecting its large genome, introns were considerably larger than other free-living flatworms, but evidence of abundant transposable elements suggests genome expansion has been principally via transposable elements activity. This genome resource will be of great use for future developmental and phylogenomic research.