scholarly journals Paleozoic Protein Fossils Illuminate the Evolution of Vertebrate Genomes and Transposable Elements

2021 ◽  
Author(s):  
Martin C Frith
Keyword(s):  
Transposable Elements ◽  
Common Ancestor ◽  
Regulatory Elements ◽  
Regulatory Function ◽  
Last Common Ancestor ◽  
Protein Coding ◽  
New Genes ◽  
Gene Regulatory ◽  
Host Genes ◽  
The Way

Genomes hold a treasure trove of protein fossils: fragments of formerly protein-coding DNA, which mainly come from transposable elements (TEs) or host genes. These fossils reveal ancient evolution of TEs and genomes, and many fossils have been exapted to perform diverse functions important for the host's fitness. However, old and highly-degraded fossils are hard to identify, and standard methods (e.g. BLAST) are not optimized for this task. Here, a recently optimized method is used to find protein fossils in vertebrate genomes. It finds Paleozoic fossils predating the amphibian/amniote divergence from most major TE categories, including virus-related Polinton and Gypsy elements. It finds 10 fossils in the human genome (8 from TEs and 2 from host genes) that predate the last common ancestor of all jawed vertebrates, probably from the Ordovician period. It also finds types of transposon and retrotransposon not found in human before. These fossils have extreme sequence conservation, indicating exaptation: some have evidence of gene-regulatory function, and they tend to lie nearest to developmental genes. Some ancient fossils suggest "genome tectonics", where two fragments of one TE have drifted apart by up to megabases, possibly explaining gene deserts and large introns. This paints a picture of great TE diversity in our aquatic ancestors, with patchy TE inheritance by later vertebrates, producing new genes and regulatory elements on the way. Host-gene fossils too have contributed anciently-conserved DNA segments. This paves the way to further studies of ancient protein fossils.

scholarly journals Host Gene Regulation by Transposable Elements: The New, the Old and the Ugly

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1089 ◽  
Author(s):  
Rocio Enriquez-Gasca ◽  
Poppy A. Gould ◽  
Helen M. Rowe
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Transposable Elements ◽  
Essential Gene ◽  
Expression Patterns ◽  
Genetic Material ◽  
Endogenous Retroviruses ◽  
Host Gene ◽  
New Genes ◽  
Host Genes

The human genome has been under selective pressure to evolve in response to emerging pathogens and other environmental challenges. Genome evolution includes the acquisition of new genes or new isoforms of genes and changes to gene expression patterns. One source of genome innovation is from transposable elements (TEs), which carry their own promoters, enhancers and open reading frames and can act as ‘controlling elements’ for our own genes. TEs include LINE-1 elements, which can retrotranspose intracellularly and endogenous retroviruses (ERVs) that represent remnants of past retroviral germline infections. Although once pathogens, ERVs also represent an enticing source of incoming genetic material that the host can then repurpose. ERVs and other TEs have coevolved with host genes for millions of years, which has allowed them to become embedded within essential gene expression programmes. Intriguingly, these host genes are often subject to the same epigenetic control mechanisms that evolved to combat the TEs that now regulate them. Here, we illustrate the breadth of host gene regulation through TEs by focusing on examples of young (The New), ancient (The Old), and disease-causing (The Ugly) TE integrants.

scholarly journals Transposable elements as a potent source of diverse cis -regulatory sequences in mammalian genomes

2020 ◽  
Vol 375 (1795) ◽  
pp. 20190347 ◽  
Author(s):  
Vasavi Sundaram ◽  
Joanna Wysocka
Keyword(s):  
Gene Regulation ◽  
Transposable Elements ◽  
Regulatory Networks ◽  
Regulatory Elements ◽  
Regulatory Function ◽  
Specific Gene ◽  
Regulatory Sequences ◽  
Dependent Manner ◽  
Unique Contribution ◽  
Regulatory Potential

Eukaryotic gene regulation is mediated by cis -regulatory elements, which are embedded within the vast non-coding genomic space and recognized by the transcription factors in a sequence- and context-dependent manner. A large proportion of eukaryotic genomes, including at least half of the human genome, are composed of transposable elements (TEs), which in their ancestral form carried their own cis -regulatory sequences able to exploit the host trans environment to promote TE transcription and facilitate transposition. Although not all present-day TE copies have retained this regulatory function, the preexisting regulatory potential of TEs can provide a rich source of cis -regulatory innovation for the host. Here, we review recent evidence documenting diverse contributions of TE sequences to gene regulation by functioning as enhancers, promoters, silencers and boundary elements. We discuss how TE-derived enhancer sequences can rapidly facilitate changes in existing gene regulatory networks and mediate species- and cell-type-specific regulatory innovations, and we postulate a unique contribution of TEs to species-specific gene expression divergence in pluripotency and early embryogenesis. With advances in genome-wide technologies and analyses, systematic investigation of TEs' cis -regulatory potential is now possible and our understanding of the biological impact of genomic TEs is increasing. This article is part of a discussion meeting issue ‘Crossroads between transposons and gene regulation’.

scholarly journals Mutations in gene regulatory elements linked to human limb malformations

2019 ◽  
Vol 57 (6) ◽  
pp. 361-370
Author(s):  
Karol Nowosad ◽  
Ewa Hordyjewska-Kowalczyk ◽  
Przemko Tylzanowski
Keyword(s):  
Regulatory Elements ◽  
Regulatory Function ◽  
Protein Coding ◽  
Coding Regions ◽  
Technological Advances ◽  
Non Coding Rna ◽  
Limb Malformations ◽  
Gene Regulatory Elements ◽  
Chromatin Organisation ◽  
Human Limb

Most of the human genome has a regulatory function in gene expression. The technological progress made in recent years permitted the revision of old and discovery of new mutations outside of the protein-coding regions that do affect human limb morphology. Steadily increasing discovery rate of such mutations suggests that until now the largely neglected part of the genome rises to its well-deserved prominence. In this review, we describe the recent technological advances permitting this unprecedented advance in identifying non-coding mutations. We especially focus on the mutations in cis-regulatory elements such as enhancers, and trans-regulatory elements such as miRNA and long non-coding RNA, linked to hereditary or inborn limb defects. We also discuss the role of chromatin organisation and enhancer–promoter interactions in the aetiology of limb malformations.

scholarly journals Developmental constraints on genome evolution in four bilaterian model species

2017 ◽  
Author(s):  
Jialin Liu ◽  
Marc Robinson-Rechavi
Keyword(s):  
Genome Evolution ◽  
Purifying Selection ◽  
Regulatory Elements ◽  
Sequence Evolution ◽  
Late Development ◽  
Developmental Constraints ◽  
Protein Coding ◽  
New Genes ◽  
Hourglass Model ◽  
Conservation Model

AbstractDevelopmental constraints on genome evolution have been suggested to follow either an early conservation model or an “hourglass” model. Both models agree that late development strongly diverges between species, but debate on which developmental period is the most conserved. Here, based on a modified “Transcriptome Age Index” approach, i.e. weighting trait measures by expression level, we analyzed the constraints acting on three evolutionary traits of protein coding genes (strength of purifying selection on protein sequences, phyletic age, and duplicability) in four species: nematode worm Caenorhabditis elegans, fly Drosophila melanogaster, zebrafish Danio rerio, and mouse Mus musculus. In general, we found that both models can be supported by different genomic properties. Sequence evolution follows an hourglass model, but the evolution of phyletic age and of duplicability follow an early conservation model. Further analyses indicate that stronger purifying selection on sequences in the middle development are driven by temporal pleiotropy of these genes. In addition, we report evidence that expression in late development is enriched with retrogenes, which usually lack efficient regulatory elements. This implies that expression in late development could facilitate transcription of new genes, and provide opportunities for acquisition of function. Finally, in C. elegans, we suggest that dosage imbalance could be one of the main factors that cause depleted expression of high duplicability genes in early development.

scholarly journals A Reassessment of Copy Number Variations in Congenital Heart Defects: Picturing the Whole Genome

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1048
Author(s):  
Ilse Meerschaut ◽  
Sarah Vergult ◽  
Annelies Dheedene ◽  
Björn Menten ◽  
Katya De Groote ◽  
...  
Keyword(s):  
Copy Number ◽  
Congenital Heart ◽  
Heart Defects ◽  
Regulatory Elements ◽  
Copy Number Variations ◽  
Related Gene ◽  
Protein Coding ◽  
Gene Enhancer ◽  
Gene Regulatory Elements ◽  
Gene Regulatory

Copy number variations (CNVs) can modulate phenotypes by affecting protein-coding sequences directly or through interference of gene expression. Recent studies in cancer and limb defects pinpointed the relevance of non-coding gene regulatory elements such as long non-coding RNAs (lncRNAs) and topologically associated domain (TAD)-related gene-enhancer interactions. The contribution of such non-coding elements is largely unexplored in congenital heart defects (CHD). We performed a retrospective analysis of CNVs reported in a cohort of 270 CHD patients. We reviewed the diagnostic yield of pathogenic CNVs, and performed a comprehensive reassessment of 138 CNVs of unknown significance (CNV-US), evaluating protein-coding genes, lncRNA genes, and potential interferences with TAD-related gene-enhancer interactions. Fifty-two of the 138 CNV-US may relate to CHD, revealing three candidate CHD regions, 19 candidate CHD genes, 80 lncRNA genes of interest, and six potentially CHD-related TAD interferences. Our study thus indicates a potential relevance of non-coding gene regulatory elements in CNV-related CHD pathogenesis. Shortcomings in our current knowledge on genomic variation call for continuous reporting of CNV-US in international databases, careful patient counseling, and additional functional studies to confirm these preliminary findings.

scholarly journals Analysis of fungal genomes reveals commonalities of intron gain or loss and functions in intron-poor species

2021 ◽  
Author(s):  
Chun Shen Lim ◽  
Brooke N Weinstein ◽  
Scott W Roy ◽  
Chris M Brown
Keyword(s):  
Ribosome Biogenesis ◽  
Evolutionary History ◽  
Common Ancestor ◽  
Intron Loss ◽  
Fungal Species ◽  
Last Common Ancestor ◽  
Intron Evolution ◽  
Protein Coding ◽  
Genes Encoding ◽  
Fungal Genomes

Abstract Previous evolutionary reconstructions have concluded that early eukaryotic ancestors including both the last common ancestor of eukaryotes and of all fungi had intron-rich genomes. By contrast, some extant eukaryotes have few introns, underscoring the complex histories of intron-exon structures, and raising the question as to why these few introns are retained. Here we have used recently available fungal genomes to address a variety of questions related to intron evolution. Evolutionary reconstruction of intron presence and absence using 263 diverse fungal species supports the idea that massive intron reduction through intron loss has occurred in multiple clades. The intron densities estimated in various fungal ancestors differ from zero to 7.6 introns per one kbp of protein-coding sequence. Massive intron loss has occurred not only in microsporidian parasites and saccharomycetous yeasts, but also in diverse smuts and allies. To investigate the roles of the remaining introns in highly-reduced species, we have searched for their special characteristics in eight intron-poor fungi. Notably, the introns of ribosome associated genes RPL7 and NOG2 have conserved positions; both intron-containing genes encoding snoRNAs. Furthermore, both the proteins and snoRNAs are involved in ribosome biogenesis, suggesting that the expression of the protein-coding genes and non-coding snoRNAs may be functionally coordinated. Indeed, these introns are also conserved in three-quarters of fungi species. Our study shows that fungal introns have a complex evolutionary history and underappreciated roles in gene expression.

scholarly journals ENDOGENOUS RETROVIRUSES AS GENETIC MODULES THAT SHAPE THE GENOME REGULATORY NETWORKS DURING EVOLUTION

2018 ◽  
Keyword(s):  
Regulatory Networks ◽  
Gene Activation ◽  
Cell Types ◽  
Regulatory Elements ◽  
Endogenous Retroviruses ◽  
Protein Coding ◽  
Transcriptional Enhancers ◽  
Wide Range ◽  
Gene Regulatory Elements ◽  
Gene Regulatory

Endogenous retroviruses (ERV) are the descendants of exogenous retroviruses that integrated into the germ cells genome, fixed and became inheritable. ERVs have evolved transcriptional enhancers and promoters that allow their replication in a wide range of tissue. Because ERVs comprise the regulatory elements it could be assume that ERVs capable to shape and reshape genomic regulatory networks by inserting their promoters and enhancers in new genomic loci upon retrotransposition. Thus retroransposition events can build new regulatory regions and lead to a new pattern of gene activation in the cell. In this review we summarize evidence which revealed that ERVs provide a plethora of novel gene regulatory elements, including tissue specific promoters and enhancers for protein-coding genes or long noncoding RNAs in a wide range of cell types. The accumulated findings support the hypothesis that the ERVs have rewired the gene regulatory networks and act as a major source of genomic regulatory innovation during evolution.

scholarly journals The Structural, Functional and Evolutionary Impact of Transposable Elements in Eukaryotes

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 918
Author(s):  
Dareen Almojil ◽  
Yann Bourgeois ◽  
Marcin Falis ◽  
Imtiyaz Hariyani ◽  
Justin Wilcox ◽  
...  
Keyword(s):  
Transposable Elements ◽  
Regulatory Networks ◽  
Biological Processes ◽  
Structural Rearrangements ◽  
Protein Coding ◽  
Vast Number ◽  
Haploid Genome Size ◽  
Genomic Regions ◽  
The Impact ◽  
Host Genes

Transposable elements (TEs) are nearly ubiquitous in eukaryotes. The increase in genomic data, as well as progress in genome annotation and molecular biology techniques, have revealed the vast number of ways mobile elements have impacted the evolution of eukaryotes. In addition to being the main cause of difference in haploid genome size, TEs have affected the overall organization of genomes by accumulating preferentially in some genomic regions, by causing structural rearrangements or by modifying the recombination rate. Although the vast majority of insertions is neutral or deleterious, TEs have been an important source of evolutionary novelties and have played a determinant role in the evolution of fundamental biological processes. TEs have been recruited in the regulation of host genes and are implicated in the evolution of regulatory networks. They have also served as a source of protein-coding sequences or even entire genes. The impact of TEs on eukaryotic evolution is only now being fully appreciated and the role they may play in a number of biological processes, such as speciation and adaptation, remains to be deciphered.

scholarly journals Effects of gene regulatory reprogramming on gene expression in human and mouse developing hearts

2013 ◽  
Vol 368 (1620) ◽  
pp. 20120366 ◽  
Author(s):  
Chih-Hao Hsu ◽  
Ivan Ovcharenko
Keyword(s):  
Large Scale ◽  
Mouse Genome ◽  
Regulatory Elements ◽  
Class Ii ◽  
Regulatory Function ◽  
Mouse Heart ◽  
Class Iii ◽  
Gene Regulatory ◽  
Human And Mouse ◽  
Human Specific

Lineage-specific regulatory elements underlie adaptation of species and play a role in disease susceptibility. We compared functionally conserved and lineage-specific enhancers by cross-mapping 5042 human and 6564 mouse heart enhancers. Of these, 79 per cent are lineage-specific, lacking a functional orthologue. Heart enhancers tend to cluster and, commonly, there are multiple heart enhancers in a heart locus providing a regulatory stability to the locus. We observed little cross-clustering, however, between lineage-specific and functionally conserved heart enhancers suggesting regulatory function acquisition and development in loci previously lacking heart activity. We also identified 862 human-specific heart enhancers: 417 featuring sequence conservation with mouse (class II) and 445 with neither sequence nor function conservation (class III). Ninety-eight per cent of class III enhancers were deleted from the mouse genome, and we estimated a similar-sized enhancer gain in the human lineage. Human-specific enhancers display no detectable decrease in the negative selection pressure and are strongly associated with genes partaking in the heart regulatory programmes. The loss of a heart enhancer could be compensated by activity of a redundant heart enhancer; however, we observed redundancy in only 15 per cent of class II and III enhancer loci indicating a large-scale reprogramming of the heart regulatory programme in mammals.

scholarly journals Mobility connects: transposable elements wire new transcriptional networks by transferring transcription factor binding motifs

2020 ◽  
Vol 48 (3) ◽  
pp. 1005-1017
Author(s):  
Yichun Qiu ◽  
Claudia Köhler
Keyword(s):  
Transcription Factors ◽  
Transposable Elements ◽  
Stress Responses ◽  
Wide Spectrum ◽  
Regulatory Elements ◽  
Regulatory Control ◽  
Transcriptional Networks ◽  
Binding Motifs ◽  
Gene Regulatory ◽  
Evolutionary Novelties

Transposable elements (TEs) constitute major fractions of plant genomes. Their potential to be mobile provides them with the capacity to cause major genome rearrangements. Those effects are potentially deleterious and enforced the evolution of epigenetic suppressive mechanisms controlling TE activity. However, beyond their deleterious effects, TE insertions can be neutral or even advantageous for the host, leading to long-term retention of TEs in the host genome. Indeed, TEs are increasingly recognized as major drivers of evolutionary novelties by regulating the expression of nearby genes. TEs frequently contain binding motifs for transcription factors and capture binding motifs during transposition, which they spread through the genome by transposition. Thus, TEs drive the evolution and diversification of gene regulatory networks by recruiting lineage-specific targets under the regulatory control of specific transcription factors. This process can explain the rapid and repeated evolution of developmental novelties, such as C4 photosynthesis and a wide spectrum of stress responses in plants. It also underpins the convergent evolution of embryo nourishing tissues, the placenta in mammals and the endosperm in flowering plants. Furthermore, the gene regulatory network underlying flower development has also been largely reshaped by TE-mediated recruitment of regulatory elements; some of them being preserved across long evolutionary timescales. In this review, we highlight the potential role of TEs as evolutionary toolkits in plants by showcasing examples of TE-mediated evolutionary novelties.

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