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Philosophical Transactions of the Royal... Feb 2017Gene duplications and gene losses have been frequent events in the evolution of animal genomes, with the balance between these two dynamic processes contributing to... (Review)
Review
Gene duplications and gene losses have been frequent events in the evolution of animal genomes, with the balance between these two dynamic processes contributing to major differences in gene number between species. After gene duplication, it is common for both daughter genes to accumulate sequence change at approximately equal rates. In some cases, however, the accumulation of sequence change is highly uneven with one copy radically diverging from its paralogue. Such 'asymmetric evolution' seems commoner after tandem gene duplication than after whole-genome duplication, and can generate substantially novel genes. We describe examples of asymmetric evolution in duplicated homeobox genes of moths, molluscs and mammals, in each case generating new homeobox genes that were recruited to novel developmental roles. The prevalence of asymmetric divergence of gene duplicates has been underappreciated, in part, because the origin of highly divergent genes can be difficult to resolve using standard phylogenetic methods.This article is part of the themed issue 'Evo-devo in the genomics era, and the origins of morphological diversity'.
Topics: Animals; Biological Evolution; Evolution, Molecular; Genes, Duplicate; Genes, Homeobox; Growth and Development
PubMed: 27994121
DOI: 10.1098/rstb.2015.0480 -
Cell Dec 2023Super-enhancers are compound regulatory elements that control expression of key cell identity genes. They recruit high levels of tissue-specific transcription factors...
Super-enhancers are compound regulatory elements that control expression of key cell identity genes. They recruit high levels of tissue-specific transcription factors and co-activators such as the Mediator complex and contact target gene promoters with high frequency. Most super-enhancers contain multiple constituent regulatory elements, but it is unclear whether these elements have distinct roles in activating target gene expression. Here, by rebuilding the endogenous multipartite α-globin super-enhancer, we show that it contains bioinformatically equivalent but functionally distinct element types: classical enhancers and facilitator elements. Facilitators have no intrinsic enhancer activity, yet in their absence, classical enhancers are unable to fully upregulate their target genes. Without facilitators, classical enhancers exhibit reduced Mediator recruitment, enhancer RNA transcription, and enhancer-promoter interactions. Facilitators are interchangeable but display functional hierarchy based on their position within a multipartite enhancer. Facilitators thus play an important role in potentiating the activity of classical enhancers and ensuring robust activation of target genes.
Topics: Enhancer Elements, Genetic; Promoter Regions, Genetic; Super Enhancers; Transcription Factors; Transcription, Genetic; alpha-Globins; Gene Expression Regulation
PubMed: 38101409
DOI: 10.1016/j.cell.2023.11.030 -
Genomics Mar 2021Here, 38 wheat PYL genes (TaPYLs) belonging to 13 homoeologous groups were identified using the genome-search method, with 26 and 12 PYL genes identified in Triticum...
Here, 38 wheat PYL genes (TaPYLs) belonging to 13 homoeologous groups were identified using the genome-search method, with 26 and 12 PYL genes identified in Triticum dicoccoides and Aegilops tauschii, respectively. Phylogenetic relationship, conserved domain and molecular evolution analysis revealed that PYL genes showed highly conservative between wheat and theprogenitors. Interaction network and miRNA target prediction found that TaPYLs could interact with the important components of ABA signaling pathway and Tae-miR966b-3p might be a hub regulator mediating wheat ABA signal network. Furthermore, the tissue-specific and stress-responsive TaPYLs were detected through RNA-seq analysis. Expressions of 10 TaPYLs were validated by QPCR analysis and the homoeologous genes showed significantly differential expression, suggesting subfunctionalization of them has occurred. Finally, 3D structures of the TaPYL proteins were predicted by homology modeling. This study lays the foundation for further functional study of PYL genes for development and stress tolerance improvement in wheat and beyond.
Topics: Conserved Sequence; Evolution, Molecular; Exons; Introns; Multigene Family; Plant Proteins; Protein Domains; Triticum
PubMed: 33321205
DOI: 10.1016/j.ygeno.2020.12.017 -
The Plant Journal : For Cell and... Feb 2018Pseudogenes have a reputation of being 'evolutionary relics' or 'junk DNA'. While they are well characterized in mammals, studies in more complex plant genomes have so...
Pseudogenes have a reputation of being 'evolutionary relics' or 'junk DNA'. While they are well characterized in mammals, studies in more complex plant genomes have so far been hampered by the absence of reference genome sequences. Barley is one of the economically most important cereals and has a genome size of 5.1 Gb. With the first high-quality genome reference assembly available for a Triticeae crop, we conducted a whole-genome assessment of pseudogenes on the barley genome. We identified, characterized and classified 89 440 gene fragments and pseudogenes scattered along the chromosomes, with occasional hotspots and higher densities at the chromosome ends. Full-length pseudogenes (11 015) have preferentially retained their exon-intron structure. Retrotransposition of processed mRNAs only plays a marginal role in their creation. However, the distribution of retroposed pseudogenes reflects the Rabl configuration of barley chromosomes and thus hints at founding mechanisms. While parent genes related to the defense-response were found to be under-represented in cultivated barley, we detected several defense-related pseudogenes in wild barley accessions. The percentage of transcriptionally active pseudogenes is 7.2%, and these may potentially adopt new regulatory roles.The barley genome is rich in pseudogenes and small gene fragments mainly located towards chromosome tips or as tandemly repeated units. Our results indicate non-random duplication and pseudogenization preferences and improve our understanding of the dynamics of gene birth and death in large plant genomes and the mechanisms that lead to evolutionary innovations.
Topics: Chromosome Mapping; Chromosomes, Plant; Gene Duplication; Genes, Plant; Hordeum; Multigene Family; Pseudogenes; Selection, Genetic; Synteny
PubMed: 29205595
DOI: 10.1111/tpj.13794 -
Journal of Mathematical Biology Jun 2019Best match graphs arise naturally as the first processing intermediate in algorithms for orthology detection. Let T be a phylogenetic (gene) tree T and [Formula: see...
Best match graphs arise naturally as the first processing intermediate in algorithms for orthology detection. Let T be a phylogenetic (gene) tree T and [Formula: see text] an assignment of leaves of T to species. The best match graph [Formula: see text] is a digraph that contains an arc from x to y if the genes x and y reside in different species and y is one of possibly many (evolutionary) closest relatives of x compared to all other genes contained in the species [Formula: see text]. Here, we characterize best match graphs and show that it can be decided in cubic time and quadratic space whether [Formula: see text] derived from a tree in this manner. If the answer is affirmative, there is a unique least resolved tree that explains [Formula: see text], which can also be constructed in cubic time.
Topics: Algorithms; Biological Evolution; Computer Graphics; Genes; Humans; Models, Genetic; Phylogeny
PubMed: 30968198
DOI: 10.1007/s00285-019-01332-9 -
Annual Review of Genomics and Human... Aug 2022The successful development and ongoing functioning of complex organisms depend on the faithful execution of the genetic code. A critical step in this process is the... (Review)
Review
The successful development and ongoing functioning of complex organisms depend on the faithful execution of the genetic code. A critical step in this process is the correct spatial and temporal expression of genes. The highly orchestrated transcription of genes is controlled primarily by regulatory elements: promoters, enhancers, and insulators. The medical importance of this key biological process can be seen by the frequency with which mutations and inherited variants that alter regulatory elements lead to monogenic and complex diseases and cancer. Here, we provide an overview of the methods available to characterize and perturb gene regulatory circuits. We then highlight mechanisms through which regulatory rewiring contributes to disease, and conclude with a perspective on how our understanding of gene regulation can be used to improve human health.
Topics: Enhancer Elements, Genetic; Gene Expression Regulation; Gene Regulatory Networks; Humans; Mutation; Promoter Regions, Genetic
PubMed: 35472292
DOI: 10.1146/annurev-genom-112921-010715 -
FEMS Microbiology Reviews May 2022Essential genes encode the processes that are necessary for life. Until recently, commonly applied binary classifications left no space between essential and... (Review)
Review
Essential genes encode the processes that are necessary for life. Until recently, commonly applied binary classifications left no space between essential and non-essential genes. In this review, we frame bacterial gene essentiality in the context of genetic networks. We explore how the quantitative properties of gene essentiality are influenced by the nature of the encoded process, environmental conditions and genetic background, including a strain's distinct evolutionary history. The covered topics have important consequences for antibacterials, which inhibit essential processes. We argue that the quantitative properties of essentiality can thus be used to prioritize antibacterial cellular targets and desired spectrum of activity in specific infection settings. We summarize our points with a case study on the core essential genome of the cystic fibrosis pathobiome and highlight avenues for targeted antibacterial development.
Topics: Anti-Bacterial Agents; DNA Transposable Elements; Genes, Bacterial; Genes, Essential
PubMed: 35104846
DOI: 10.1093/femsre/fuac005 -
PLoS Genetics May 2021Fisher's partitioning of genotypic values and genetic variance is highly relevant in the current era of genome-wide association studies (GWASs). However, despite being... (Review)
Review
Fisher's partitioning of genotypic values and genetic variance is highly relevant in the current era of genome-wide association studies (GWASs). However, despite being more than a century old, a number of persistent misconceptions related to nonadditive genetic effects remain. We developed a user-friendly web tool, the Falconer ShinyApp, to show how the combination of gene action and allele frequencies at causal loci translate to genetic variance and genetic variance components for a complex trait. The app can be used to demonstrate the relationship between a SNP effect size estimated from GWAS and the variation the SNP generates in the population, i.e., how locus-specific effects lead to individual differences in traits. In addition, it can also be used to demonstrate how within and between locus interactions (dominance and epistasis, respectively) usually do not lead to a large amount of nonadditive variance relative to additive variance, and therefore, that these interactions usually do not explain individual differences in a population.
Topics: Epistasis, Genetic; Gene Frequency; Genes; Genes, Dominant; Genetic Loci; Genetic Variation; Genome-Wide Association Study; Genotype; Humans; Internet; Models, Genetic; Polymorphism, Single Nucleotide; Software
PubMed: 34014919
DOI: 10.1371/journal.pgen.1009548 -
BioEssays : News and Reviews in... Oct 2016Mutations in enhancer-associated chromatin-modifying components and genomic alterations in non-coding regions of the genome occur frequently in cancer, and other... (Review)
Review
Mutations in enhancer-associated chromatin-modifying components and genomic alterations in non-coding regions of the genome occur frequently in cancer, and other diseases pointing to the importance of enhancer fidelity to ensure proper tissue homeostasis. In this review, I will use specific examples to discuss how mutations in chromatin-modifying factors might affect enhancer activity of disease-relevant genes. I will then consider direct evidence from single nucleotide polymorphisms, small insertions, or deletions but also larger genomic rearrangements such as duplications, deletions, translocations, and inversions of specific enhancers to demonstrate how they have the ability to impact enhancer activity of disease genes including oncogenes and tumor suppressor genes. Considering that the scientific community only fairly recently has begun to focus its attention on "enhancer malfunction" in disease, I propose that multiple new enhancer-regulated and disease-relevant processes will be uncovered in the near future that will constitute the mechanistic basis for novel therapeutic avenues.
Topics: Animals; Enhancer Elements, Genetic; Gene Expression Regulation, Neoplastic; Genes, Neoplasm; Humans; Mutation; Neoplasms
PubMed: 27570183
DOI: 10.1002/bies.201600106 -
Journal of Neuromuscular Diseases 2023Three decades since the Human Genome Project began, scientists have now identified more then 25,000 protein coding genes in the human genome. The vast majority of the... (Review)
Review
Three decades since the Human Genome Project began, scientists have now identified more then 25,000 protein coding genes in the human genome. The vast majority of the protein coding genes (> 90%) are multi-exonic, with the coding DNA being interrupted by intronic sequences, which are removed from the pre-mRNA transcripts before being translated into proteins, a process called splicing maturation. Variations in this process, i.e. by exon skipping, intron retention, alternative 5' splice site (5'ss), 3' splice site (3'ss), or polyadenylation usage, lead to remarkable transcriptome and proteome diversity in human tissues. Given its critical biological importance, alternative splicing is tightly regulated in a tissue- and developmental stage-specific manner. The central nervous system and skeletal muscle are amongst the tissues with the highest number of differentially expressed alternative exons, revealing a remarkable degree of transcriptome complexity. It is therefore not surprising that splicing mis-regulation is causally associated with a myriad of neuromuscular diseases, including but not limited to amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), Duchenne muscular dystrophy (DMD), and myotonic dystrophy type 1 and 2 (DM1, DM2). A gene's transcript diversity has since become an integral and an important consideration for drug design, development and therapy. In this review, we will discuss transcript diversity in the context of neuromuscular diseases and current approaches to address splicing mis-regulation.
Topics: Humans; RNA Splice Sites; Alternative Splicing; RNA Splicing; Exons; Introns
PubMed: 37182892
DOI: 10.3233/JND-221601