scholarly journals Comparative genomics within and across Bilaterians illuminates the evolutionary history of ALK and LTK proto-oncogene origination and diversification

Author(s):  
Alex Dornburg ◽  
Zheng Wang ◽  
Junrui Wang ◽  
Elizabeth S Mo ◽  
Francesc Lopez-Giraldez ◽  
...  

Abstract Comparative genomic analyses have enormous potential for identifying key genes central to human health phenotypes, including those that promote cancers. In particular, the successful development of novel therapeutics using model species requires phylogenetic analyses to determine molecular homology. Accordingly, we investigate the evolutionary histories of anaplastic lymphoma kinase (ALK)—which can underlie tumorigenesis in neuroblastoma, non-small cell lung cancer, and anaplastic large-cell lymphoma—its close relative leukocyte tyrosine kinase (LTK) and their candidate ligands. Homology of ligands identified in model organisms to those functioning in humans remains unclear. Therefore, we searched for homologs of the human genes across metazoan genomes, finding that the candidate ligands Jeb and Hen-1 were restricted to non-vertebrate species. In contrast, the ligand AUG was only identified in vertebrates. We found two ALK-like and four AUG-like protein-coding genes in lamprey. Of these six genes, only one ALK-like and two AUG-like genes exhibited early embryonic expression that parallels model mammal systems. Two copies of AUG are present in nearly all jawed vertebrates. Our phylogenetic analysis strongly supports the presence of previously unrecognized functional convergences of ALK and LTK between actinopterygians and sarcopterygians—despite contemporaneous, highly conserved synteny of ALK and LTK. These findings provide critical guidance regarding the propriety of fish and mammal models with regard to model-organism-based investigation of these medically important genes. In sum, our results provide the phylogenetic context necessary for effective investigations of the functional roles and biology of these critically important receptors.

Insects ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 754
Author(s):  
Yupeng Wu ◽  
Hui Fang ◽  
Jiping Wen ◽  
Juping Wang ◽  
Tianwen Cao ◽  
...  

In this study, the complete mitochondrial genomes (mitogenomes) of Hestina persimilis and Hestinalis nama (Nymphalidae: Apaturinae)were acquired. The mitogenomes of H. persimilis and H. nama are 15,252 bp and 15,208 bp in length, respectively. These two mitogenomes have the typical composition, including 37 genes and a control region. The start codons of the protein-coding genes (PCGs) in the two mitogenomes are the typical codon pattern ATN, exceptCGA in the cox1 gene. Twenty-one tRNA genes show a typical clover leaf structure, however, trnS1(AGN) lacks the dihydrouridine (DHU) stem. The secondary structures of rrnL and rrnS of two species were predicted, and there are several new stem loops near the 5’ of rrnL secondary structure. Based on comparative genomic analysis, four similar conservative structures can be found in the control regions of these two mitogenomes. The phylogenetic analyses were performed on mitogenomes of Nymphalidae. The phylogenetic trees show that the relationships among Nymphalidae are generally identical to previous studies, as follows: Libytheinae\Danainae + ((Calinaginae + Satyrinae) + Danainae\Libytheinae + ((Heliconiinae + Limenitidinae) + (Nymphalinae + (Apaturinae + Biblidinae)))). Hestinalisnama isapart fromHestina, andclosely related to Apatura, forming monophyly.


BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Yu Zhao ◽  
Dantong Shang ◽  
Ruhong Ying ◽  
Hanhua Cheng ◽  
Rongjia Zhou

Abstract Background Zebrafish is a model organism widely used for the understanding of gene function, including the fundamental basis of human disease, enabled by the presence in its genome of a high number of orthologs to human genes. CRISPR/Cas9 and next-generation gene-editing techniques using cytidine deaminase fused with Cas9 nickase provide fast and efficient tools able to induce sequence-specific single base mutations in various organisms and have also been used to generate genetically modified zebrafish for modeling pathogenic mutations. However, the editing efficiency in zebrafish of currently available base editors is lower than other model organisms, frequently inducing indel formation, which limits the applicability of these tools and calls for the search of more accurate and efficient editors. Results Here, we generated a new base editor (zAncBE4max) with a length of 5560 bp following a strategy based on the optimization of codon preference in zebrafish. Our new editor effectively created C-to-T base substitution while maintaining a high product purity at multiple target sites. Moreover, zAncBE4max successfully generated the Twist2 p.E78K mutation in zebrafish, recapitulating pathological features of human ablepharon macrostomia syndrome (AMS). Conclusions Overall, the zAncBE4max system provides a promising tool to perform efficient base editing in zebrafish and enhances its capacity to precisely model human diseases.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xia Xue ◽  
Anton Suvorov ◽  
Stanley Fujimoto ◽  
Adler R Dilman ◽  
Byron J Adams

Abstract Plectus murrayi is one of the most common and locally abundant invertebrates of continental Antarctic ecosystems. Because it is readily cultured on artificial medium in the laboratory and highly tolerant to an extremely harsh environment, P. murrayi is emerging as a model organism for understanding the evolutionary origin and maintenance of adaptive responses to multiple environmental stressors, including freezing and desiccation. The de novo assembled genome of P. murrayi contains 225.741 million base pairs and a total of 14,689 predicted genes. Compared to Caenorhabditis elegans, the architectural components of P. murrayi are characterized by a lower number of protein-coding genes, fewer transposable elements, but more exons, than closely related taxa from less harsh environments. We compared the transcriptomes of lab-reared P. murrayi with wild-caught P. murrayi and found genes involved in growth and cellular processing were up-regulated in lab-cultured P. murrayi, while a few genes associated with cellular metabolism and freeze tolerance were expressed at relatively lower levels. Preliminary comparative genomic and transcriptomic analyses suggest that the observed constraints on P. murrayi genome architecture and functional gene expression, including genome decay and intron retention, may be an adaptive response to persisting in a biotically simplified, yet consistently physically harsh environment.


2021 ◽  
Vol 9 (7) ◽  
pp. 1488
Author(s):  
Anna Grankvist ◽  
Daniel Jaén-Luchoro ◽  
Linda Wass ◽  
Per Sikora ◽  
Christine Wennerås

Tick-borne ‘Neoehrlichia (N.) mikurensis’ is the cause of neoehrlichiosis, an infectious vasculitis of humans. This strict intracellular pathogen is a member of the family Anaplasmataceae and has been unculturable until recently. The only available genetic data on this new pathogen are six partially sequenced housekeeping genes. The aim of this study was to advance the knowledge regarding ‘N. mikurensis’ genomic relatedness with other Anaplasmataceae members, intra-species genotypic variability and potential virulence factors explaining its tropism for vascular endothelium. Here, we present the de novo whole-genome sequences of three ‘N. mikurensis’ strains derived from Swedish patients diagnosed with neoehrlichiosis. The genomes were obtained by extraction of DNA from patient plasma, library preparation using 10x Chromium technology, and sequencing by Illumina Hiseq-4500. ‘N. mikurensis’ was found to have the next smallest genome of the Anaplasmataceae family (1.1 Mbp with 27% GC contents) consisting of 845 protein-coding genes, every third of which with unknown function. Comparative genomic analyses revealed that ‘N. mikurensis’ was more closely related to Ehrlichia chaffeensis than to Ehrlichia ruminantium, the opposite of what 16SrRNA sequence-based phylogenetic analyses determined. The genetic variability of the three whole-genome-sequenced ‘N. mikurensis’ strains was extremely low, between 0.14 and 0.22‰, a variation that was associated with geographic origin. No protein-coding genes exclusively shared by N. mikurensis and E. ruminantium were identified to explain their common tropism for vascular endothelium.


Author(s):  
Duo Chen ◽  
Xue Yuan ◽  
Xuehai Zheng ◽  
Jingping Fang ◽  
Gang Lin ◽  
...  

Isochrysis galbana is an important producer in the aquatic ecosystem because of its rich fucoxanthin content and fast growth. However, little is known about its evolutionary adaptation to live in a specific, complex and harsh environment. We report a high-quality genome sequence of I. galbana LG007, which has a 92.73 Mb genome size, a contig N50 of 6.99 Mb and 14,900 protein-coding genes. Phylogenomic inferences confirmed the monophyly of Haptophyta, showing I. galbana is a sister to E. huxleyi and C. tobinii. Evolutionary analysis revealed an estimated divergence of I. galbana from its close relative E. huxleyi ~133 million years ago, and I. galbana underwent one round of whole-genome duplication. Genes related to environmental adaptation and metabolic regulation in I. galbana were relatively conserved, but the basic transcriptional regulation toolkit for terrestrial plant development has been contracted or was not detected. The domain identification of one novel fucoxanthin biosynthesis gene that encodes diadinoxanthin-fucoxanthin hydroxylase (DFH) was investigated. Comparative genomic analysis revealed that I. galbana acquired several transcription factors specific to the control of pigment accumulation and production of LHCX2 to harvest blue-green light, which facilitates adaptation to the underwater environment. These findings provide new insights into the genomic characteristics of I. galbana and algae evolution for adaptation to blue-green light underwater.


1999 ◽  
Vol 27 (15) ◽  
pp. 3219-3228 ◽  
Author(s):  
Manyuan Long ◽  
Michael Deutsch

Abstract To investigate the distribution of intron—exon structures of eukaryotic genes, we have constructed a general exon database comprising all available introncontaining genes and exon databases from 10 eukaryotic model organisms: Homo sapiens, Mus musculus, Gallus gallus, Rattus norvegicus, Arabidopsis thaliana, Zea mays, Schizosaccharomyces pombe, Aspergillus, Caenorhabditis elegans and Drosophila . We purged redundant genes to avoid the possible bias brought about by redundancy in the databases. After discarding those questionable introns that do not contain correct splice sites, the final database contained 17 102 introns, 21 019 exons and 2903 independent or quasi-independent genes. On average, a eukaryotic gene contains 3.7 introns per kb protein coding region. The exon distribution peaks around 30–40 residues and most introns are 40–125 nt long. The variable intron—exon structures of the 10 model organisms reveal two interesting statistical phenomena, which cast light on some previous speculations. (i) Genome size seems to be correlated with total intron length per gene. For example, invertebrate introns are smaller than those of human genes, while yeast introns are shorter than invertebrate introns. However, this correlation is weak, suggesting that other factors besides genome size may also affect intron size. (ii) Introns smaller than 50 nt are significantly less frequent than longer introns, possibly resulting from a minimum intron size requirement for intron splicing.


Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 715
Author(s):  
Fengjiao Zhang ◽  
Ning Wang ◽  
Guanghao Cheng ◽  
Xiaochun Shu ◽  
Tao Wang ◽  
...  

The genus Lycoris (Amaryllidaceae) consists of about 20 species, which is endemic to East Asia. Although the Lycoris species is of great horticultural and medical importance, challenges in accurate species identification persist due to frequent natural hybridization and large-scale intraspecific variation. In this study, we sequenced chloroplast genomes of four Lycoris species and retrieved seven published chloroplast (cp) genome sequences in this genus for comparative genomic and phylogenetic analyses. The cp genomes of these four newly sequenced species were found to be 158,405–158,498 bp with the same GC content of 37.8%. The structure of the genomes exhibited the typical quadripartite structure with conserved gene order and content. A total of 113 genes (20 duplicated) were identified, including 79 protein-coding genes (PCGs), 30 tRNAs, and 4 rRNAs. Phylogenetic analysis showed that the 11 species were clustered into three main groups, and L. sprengeri locate at the base of Lycoriss. The L. radiata was suggested to be the female donor of the L. incarnata, L. shaanxiensis, and L. squamigera. The L. straminea and L. houdyshelii may be derived from L. anhuiensis, L. chinensis, or L. longituba. These results could not only offer a genome-scale platform for identification and utilization of Lycoris but also provide a phylogenomic framework for future studies in this genus.


Author(s):  
Emily K. Herman ◽  
Alex Greninger ◽  
Mark van der Giezen ◽  
Michael L. Ginger ◽  
Inmaculada Ramirez-Macias ◽  
...  

AbstractOf the 40 described Naegleria species, only N. fowleri can establish infection in humans, killing almost invariably within two weeks. In the brain, the amoeba performs piece-meal ingestion, or trogocytosis, of brain material causing massive inflammation. Conversely, its close relative Naegleria gruberi, which is used as a laboratory model organism, is non-pathogenic. The exact pathogenicity factors distinguishing N. fowleri from its harmless relatives are unclear. We have here taken an -omics approach to understanding N. fowleri biology and infection at the system level. We provide the first analysis of genomic diversity between strains, finding little conservation in synteny but high conservation in protein complement. We also demonstrate that the N. fowleri genome encodes a similarly complete cellular repertoire to that found in N. gruberi. Our comparative genomic analysis, together with a transcriptomic analysis of low versus high pathogenicity N. fowleri cultured in a mouse infection model, allowed us to construct a model of cellular systems involved in pathogenicity and furthermore provides ~500 novel candidate pathogenicity factors in this currently rare but highly fatal pathogen.


2019 ◽  
Vol 63 (8-9-10) ◽  
pp. 321-331 ◽  
Author(s):  
Salvatore Bozzaro

The social amoeba Dictyostelium discoideum has been a preferred model organism during the last 50 years, particularly for the study of cell motility and chemotaxis, phagocytosis and macropinocytosis, intercellular adhesion, pattern formation, caspase-independent cell death and more recently autophagy and social evolution. Being a soil amoeba and professional phagocyte, thus exposed to a variety of potential pathogens, D. discoideum has also proven to be a powerful genetic and cellular model for investigating host-pathogen interactions and microbial infections. The finding that the Dictyostelium genome harbours several homologs of human genes responsible for a variety of diseases has stimulated their analysis, providing new insights into the mechanism of action of the encoded proteins and in some cases into the defect underlying the disease. Recent technological developments have covered the genetic gap between mammals and non-mammalian model organisms, challenging the modelling role of the latter. Is there a future for Dictyostelium discoideum as a model organism?


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10687
Author(s):  
Joonhyung Jung ◽  
Hoang Dang Khoa Do ◽  
JongYoung Hyun ◽  
Changkyun Kim ◽  
Joo-Hwan Kim

Background Carduus, commonly known as plumeless thistles, is a genus in the Asteraceae family that exhibits both medicinal value and invasive tendencies. However, the genomic data of Carduus (i.e., complete chloroplast genomes) have not been sequenced. Methods We sequenced and assembled the chloroplast genome (cpDNA) sequences of three Carduus species using the Illumina Miseq sequencing system and Geneious Prime. Phylogenetic relationships between Carduus and related taxa were reconstructed using Maximum Likelihood and Bayesian Inference analyses. In addition, we used a single nucleotide polymorphism (SNP) in the protein coding region of the matK gene to develop molecular markers to distinguish C. crispus from C. acanthoides and C. tenuiflorus. Results The cpDNA sequences of C. crispus, C. acanthoides, and C. tenuiflorus ranged from 152,342 bp to 152,617 bp in length. Comparative genomic analysis revealed high conservation in terms of gene content (including 80 protein-coding, 30 tRNA, and four rRNA genes) and gene order within the three focal species and members of subfamily Carduoideae. Despite their high similarity, the three species differed with respect to the number and content of repeats in the chloroplast genome. Additionally, eight hotspot regions, including psbI-trnS_GCU, trnE_UUC-rpoB, trnR_UCU-trnG_UCC, psbC-trnS_UGA, trnT_UGU-trnL_UAA, psbT-psbN, petD-rpoA, and rpl16-rps3, were identified in the study species. Phylogenetic analyses inferred from 78 protein-coding and non-coding regions indicated that Carduus is polyphyletic, suggesting the need for additional studies to reconstruct relationships between thistles and related taxa. Based on a SNP in matK, we successfully developed a molecular marker and protocol for distinguishing C. crispus from the other two focal species. Our study provides preliminary chloroplast genome data for further studies on plastid genome evolution, phylogeny, and development of species-level markers in Carduus.


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