scholarly journals Pairs of Adjacent Conserved Noncoding Elements Separated by Conserved Genomic Distances Act as Cis-Regulatory Units

2018 ◽  
Vol 10 (9) ◽  
pp. 2535-2550 ◽  
Author(s):  
Lifei Li ◽  
Nicolai K H Barth ◽  
Eva Hirth ◽  
Leila Taher
2018 ◽  
Author(s):  
Manee M. Manee ◽  
John Jackson ◽  
Casey M. Bergman

AbstractHighly conserved noncoding elements (CNEs) comprise a significant proportion of the genomes of multicellular eukaryotes. The function of most CNEs remains elusive, but growing evidence indicates they are under some form of purifying selection. Noncoding regions in many species also harbor large numbers of transposable element (TE) insertions, which are typically lineage specific and depleted in exons because of their deleterious effects on gene function or expression. However, it is currently unknown whether the landscape of TE insertions in noncoding regions is random or influenced by purifying selection on CNEs. Here we combine comparative and population genomic data in Drosophila melanogaster to show that abundance of TE insertions in intronic and intergenic CNEs is reduced relative to random expectation, supporting the idea that selective constraints on CNEs eliminate a proportion of TE insertions in noncoding regions. However, we find no difference in the allele frequency spectra for polymorphic TE insertions in CNEs versus those in unconstrained spacer regions, suggesting that the distribution of fitness effects acting on observable TE insertions is similar across different functional compartments in noncoding DNA. Our results provide evidence that selective constraints on CNEs contribute to shaping the landscape of TE insertion in eukaryotic genomes, and provide further evidence supporting the conclusion that CNEs are indeed functionally constrained and not simply mutational cold spots.


BMC Genomics ◽  
2009 ◽  
Vol 10 (1) ◽  
pp. 278 ◽  
Author(s):  
Hooman K Moghadam ◽  
Moira M Ferguson ◽  
Roy G Danzmann

PLoS Genetics ◽  
2020 ◽  
Vol 16 (10) ◽  
pp. e1009173
Author(s):  
Jacob M. Daane ◽  
Juliette Auvinet ◽  
Alicia Stoebenau ◽  
Donald Yergeau ◽  
Matthew P. Harris ◽  
...  

In the frigid, oxygen-rich Southern Ocean (SO), Antarctic icefishes (Channichthyidae; Notothenioidei) evolved the ability to survive without producing erythrocytes and hemoglobin, the oxygen-transport system of virtually all vertebrates. Here, we integrate paleoclimate records with an extensive phylogenomic dataset of notothenioid fishes to understand the evolution of trait loss associated with climate change. In contrast to buoyancy adaptations in this clade, we find relaxed selection on the genetic regions controlling erythropoiesis evolved only after sustained cooling in the SO. This pattern is seen not only within icefishes but also occurred independently in other high-latitude notothenioids. We show that one species of the red-blooded dragonfish clade evolved a spherocytic anemia that phenocopies human patients with this disease via orthologous mutations. The genomic imprint of SO climate change is biased toward erythrocyte-associated conserved noncoding elements (CNEs) rather than to coding regions, which are largely preserved through pleiotropy. The drift in CNEs is specifically enriched near genes that are preferentially expressed late in erythropoiesis. Furthermore, we find that the hematopoietic marrow of icefish species retained proerythroblasts, which indicates that early erythroid development remains intact. Our results provide a framework for understanding the interactions between development and the genome in shaping the response of species to climate change.


Science ◽  
2019 ◽  
Vol 364 (6435) ◽  
pp. 74-78 ◽  
Author(s):  
Timothy B. Sackton ◽  
Phil Grayson ◽  
Alison Cloutier ◽  
Zhirui Hu ◽  
Jun S. Liu ◽  
...  

A core question in evolutionary biology is whether convergent phenotypic evolution is driven by convergent molecular changes in proteins or regulatory regions. We combined phylogenomic, developmental, and epigenomic analysis of 11 new genomes of paleognathous birds, including an extinct moa, to show that convergent evolution of regulatory regions, more so than protein-coding genes, is prevalent among developmental pathways associated with independent losses of flight. A Bayesian analysis of 284,001 conserved noncoding elements, 60,665 of which are corroborated as enhancers by open chromatin states during development, identified 2355 independent accelerations along lineages of flightless paleognaths, with functional consequences for driving gene expression in the developing forelimb. Our results suggest that the genomic landscape associated with morphological convergence in ratites has a substantial shared regulatory component.


2010 ◽  
Vol 28 (3) ◽  
pp. 1205-1215 ◽  
Author(s):  
A. P. Lee ◽  
S. Y. Kerk ◽  
Y. Y. Tan ◽  
S. Brenner ◽  
B. Venkatesh

2016 ◽  
Vol 6 (6) ◽  
pp. 1707-1712 ◽  
Author(s):  
Cristina M. Justice ◽  
Kevin Bishop ◽  
Blake Carrington ◽  
Jim C. Mullikin ◽  
Kandice Swindle ◽  
...  

2019 ◽  
Author(s):  
Ge Tan ◽  
Dimitris Polychronopoulos ◽  
Boris Lenhard

AbstractConserved Noncoding Elements (CNEs) are elements exhibiting extreme noncoding conservation in Metazoan genomes. They cluster around developmental genes and act as long-range enhancers, yet nothing that we know about their function explains the observed conservation levels. Clusters of CNEs coincide with topologically associating domains (TADs), indicating ancient origins and stability of TAD locations. This has suggested further hypotheses about the still elusive origin of CNEs, and has provided a comparative genomics-based method of estimating the position of TADs around developmentally regulated genes in genomes where chromatin conformation capture data is missing. To enable researchers in gene regulation and chromatin biology to start deciphering this phenomenon, we developedCNEr, a R/Bioconductor toolkit for large-scale identification of CNEs and for studying their genomic properties. We applyCNErto two novel genome comparisons - fruit fly vs tsetse fly, and two sea urchin genomes - and report novel insights gained from their analysis. We also show how to reveal interesting characteristics of CNEs by coupling CNEr with existing Bioconductor packages.CNEris available at Bioconductor (https://bioconductor.org/packages/CNEr/) and maintained at github (https://github.com/ge11232002/CNEr).


2018 ◽  
Author(s):  
Zhirui Hu ◽  
Timothy B. Sackton ◽  
Scott V. Edwards ◽  
Jun S. Liu

AbstractConservation of DNA sequence over evolutionary time is a strong indicator of function, and gain or loss of sequence conservation can be used to infer changes in function across a phylogeny. Changes in evolutionary rates on particular lineages in a phylogeny can indicate shared functional shifts, and thus can be used to detect genomic correlates of phenotypic convergence. However, existing methods do not allow easy detection of patterns of rate variation, which causes challenges for detecting convergent rate shifts or other complex evolutionary scenarios. Here we introduce PhyloAcc, a new Bayesian method to model substitution rate changes in conserved elements across a phylogeny. The method assumes several categories of substitution rate for each branch on the phylogenetic tree, estimates substitution rates per category, and detects changes of substitution rate as the posterior probability of a category switch. Simulations show that PhyloAcc can detect genomic regions with rate shifts in multiple target species better than previous methods and has a higher accuracy of reconstructing complex patterns of substitution rate changes than prevalent Bayesian relaxed clock models. We demonstrate the utility of PhyloAcc in two classic examples of convergent phenotypes: loss of flight in birds and the transition to marine life in mammals. In each case, our approach reveals numerous examples of conserved non-exonic elements with accelerations specific to the phenotypically convergent lineages. Our method is widely applicable to any set of conserved elements where multiple rate changes are expected on a phylogeny.


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