scholarly journals Elephant Genomes Elucidate Disease Defenses and Other Traits

2020 ◽  
Author(s):  
Marc Tollis ◽  
Elliott Ferris ◽  
Michael S. Campbell ◽  
Valerie K. Harris ◽  
Shawn M. Rupp ◽  
...  
Keyword(s):  
Population Genomics ◽  
Inflammatory Responses ◽  
Cancer Susceptibility ◽  
Purifying Selection ◽  
Regulatory Elements ◽  
Underlying Disease ◽  
Cancer Resistance ◽  
African Elephants ◽  
Genetic Mechanisms ◽  
Susceptibility And Resistance

AbstractDisease susceptibility and resistance comprise important factors in conservation, particularly in elephants. To determine genetic mechanisms underlying disease resistance and other unique elephant traits, we estimated 862 and 1,017 potential regulatory elements in Asian and African elephants, respectively. These elements are significantly enriched in both species with differentially expressed genes involved in immunity pathways, including tumor-necrosis factor which plays a role in the response to elephant endotheliotropic herpesvirus (EEHV). Population genomics analyses indicate that amplified TP53 retrogenes are maintained by purifying selection and may contribute to cancer resistance in elephants, including less malignancies in African vs. Asian elephants. Positive selection scans across elephant genomes revealed genes that may control iconic elephant traits such as tusk development, memory, and somatic maintenance. Our study supports the hypothesis that interspecies variation in gene regulation contributes to differential inflammatory responses leading to increased infectious disease and cancer susceptibility in Asian versus African elephants. Genomics can inform functional immunological studies which may improve both conservation for elephants and human therapies.

scholarly journals Elephant Genomes Reveal Accelerated Evolution in Mechanisms Underlying Disease Defenses

2021 ◽  
Author(s):  
Marc Tollis ◽  
Elliott Ferris ◽  
Michael S Campbell ◽  
Valerie K Harris ◽  
Shawn M Rupp ◽  
...  
Keyword(s):  
Cancer Susceptibility ◽  
Regulatory Elements ◽  
Underlying Disease ◽  
Asian Elephant ◽  
Cancer Resistance ◽  
African Elephants ◽  
Asian Elephants ◽  
Accelerated Evolution ◽  
Genetic Mechanisms ◽  
Conservation Of Endangered Species

Abstract Disease susceptibility and resistance are important factors for the conservation of endangered species, including elephants. We analyzed pathology data from 26 zoos and report that Asian elephants have increased neoplasia and malignancy prevalence compared with African bush elephants. This is consistent with observed higher susceptibility to tuberculosis and elephant endotheliotropic herpesvirus (EEHV) in Asian elephants. To investigate genetic mechanisms underlying disease resistance, including differential responses between species, among other elephant traits, we sequenced multiple elephant genomes. We report a draft assembly for an Asian elephant, and defined 862 and 1,017 conserved potential regulatory elements in Asian and African bush elephants, respectively. In the genomes of both elephant species, conserved elements were significantly enriched with genes differentially expressed between the species. In Asian elephants, these putative regulatory regions were involved in immunity pathways including tumor-necrosis factor, which plays an important role in EEHV response. Genomic sequences of African bush, forest, and Asian elephant genomes revealed extensive sequence conservation at TP53 retrogene loci across three species, which may be related to TP53 functionality in elephant cancer resistance. Positive selection scans revealed outlier genes related to additional elephant traits. Our study suggests that gene regulation plays an important role in the differential inflammatory response of Asian and African elephants, leading to increased infectious disease and cancer susceptibility in Asian elephants. These genomic discoveries can inform future functional and translational studies aimed at identifying effective treatment approaches for ill elephants, which may improve conservation.

Genome-wide identification, functional prediction, and evolutionary analysis of the R2R3-MYB superfamily in Brassica napus

Genome ◽  
2017 ◽  
Vol 60 (10) ◽  
pp. 797-814 ◽  
Author(s):  
Ali Hajiebrahimi ◽  
Hajar Owji ◽  
Shiva Hemmati
Keyword(s):  
Brassica Napus ◽  
Purifying Selection ◽  
Gene Clusters ◽  
Regulatory Elements ◽  
Post Inoculation ◽  
Evolutionary Analysis ◽  
Salinity Treatment ◽  
Myb Genes ◽  
R2r3 Myb ◽  
Leptosphaeria Biglobosa

R2R3-MYB transcription factors (TFs) have been shown to play important roles in plants, including in development and in various stress conditions. Phylogenetic analysis showed the presence of 249 R2R3-MYB TFs in Brassica napus, called BnaR2R3-MYB TFs, clustered into 38 clades. BnaR2R3-MYB TFs were distributed on 19 chromosomes of B. napus. Sixteen gene clusters were identified. BnaR2R3-MYB TFs were characterized by motif prediction, gene structure analysis, and gene ontology. Evolutionary analysis revealed that BnaR2R3-MYB TFs are mainly formed as a result of whole-genome duplication. Orthologs and paralogs of BnaR2R3-MYB TFs were identified in B. napus, B. rapa, B. oleracea, and Arabidopsis thaliana using synteny-based methods. Purifying selection was pervasive within R2R3-MYB TFs. Kn/Ks values lower than 0.3 indicated that BnaR2R3-MYB TFs are being functionally converged. The role of gene conversion in the formation of BnaR2R3-MYB TFs was significant. Cis-regulatory elements in the upstream regions of BnaR2R3-MYB genes, miRNA targeting BnaR2R3MYB TFs, and post translational modifications were identified. Digital expression data revealed that BnaR2R3-MYB genes were highly expressed in the roots and under high salinity treatment after 24 h. BnaMYB21, BnaMYB141, and BnaMYB148 have been suggested for improving salt-tolerant B. napus. BnaR2R3-MYB genes were mostly up regulated on the 14th day post inoculation with Leptosphaeria biglobosa and L. maculan. BnaMYB150 is a candidate for increased tolerance to Leptospheria in B. napus.

scholarly journals Comprehensive Genomic Survey, Characterization and Expression Analysis of the HECT Gene Family in Brassica rapa L. and Brassica oleracea L.

Genes ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 400 ◽  
Author(s):  
Intikhab Alam ◽  
Dong-Li Cui ◽  
Khadija Batool ◽  
Yan-Qing Yang ◽  
Yun-Hai Lu
Keyword(s):  
Brassica Oleracea ◽  
Brassica Rapa ◽  
Expression Analysis ◽  
Gene Structure ◽  
Purifying Selection ◽  
Brassica Species ◽  
Promoter Sequence ◽  
Regulatory Elements ◽  
Hect Domain ◽  
E3 Ligases

The HECT-domain protein family is one of the most important classes of E3 ligases. While the roles of this family in human diseases have been intensively studied, the information for plant HECTs is limited. In the present study, we performed the identification of HECT genes in Brassica rapa and Brassica oleracea, followed by analysis of phylogeny, gene structure, additional domains, putative cis-regulatory elements, chromosomal location, synteny, and expression. Ten and 13 HECT genes were respectively identified in B. rapa and B. oleracea and then resolved into seven groups along with their Arabidopsis orthologs by phylogenetic analysis. This classification is well supported by analyses of gene structure, motif composition within the HECT domain and additional protein domains. Ka/Ks ratio analysis showed that these HECT genes primarily underwent purifying selection with varied selection pressures resulting in different rates of evolution. RNA-Seq data analysis showed that the overwhelming majority of them were constitutively expressed in all tested tissues. qRT-PCR based expression analysis of the 10 B. rapa HECT genes under salt and drought stress conditions showed that all of them were responsive to the two stress treatments, which was consistent with their promoter sequence analysis revealing the presence of an important number of phytohormone-responsive and stress-related cis-regulatory elements. Our study provides useful information and lays the foundation for further functional determination of each HECT gene across the Brassica species.

scholarly journals Genomic determinants of speciation and spread of the Mycobacterium tuberculosis complex

2019 ◽  
Vol 5 (6) ◽  
pp. eaaw3307 ◽  
Author(s):  
Á. Chiner-Oms ◽  
L. Sánchez-Busó ◽  
J. Corander ◽  
S. Gagneux ◽  
S. R. Harris ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Population Genomics ◽  
Mycobacterium Tuberculosis Complex ◽  
Purifying Selection ◽  
Sensor Kinase ◽  
Virulence Determinants ◽  
Two Component System ◽  
Tuberculosis Complex ◽  
Bacterial Speciation ◽  
Two Component

Models on how bacterial lineages differentiate increase our understanding of early bacterial speciation events and the genetic loci involved. Here, we analyze the population genomics events leading to the emergence of the tuberculosis pathogen. The emergence is characterized by a combination of recombination events involving core pathogenesis functions and purifying selection on early diverging loci. We identify the phoR gene, the sensor kinase of a two-component system involved in virulence, as a key functional player subject to pervasive positive selection after the divergence of the Mycobacterium tuberculosis complex from its ancestor. Previous evidence showed that phoR mutations played a central role in the adaptation of the pathogen to different host species. Now, we show that phoR mutations have been under selection during the early spread of human tuberculosis, during later expansions, and in ongoing transmission events. Our results show that linking pathogen evolution across evolutionary and epidemiological time scales points to past and present virulence determinants.

scholarly journals TNF-α, TNF-β, IL-6, and IL-10 Polymorphisms in Patients with Lung Cancer

2005 ◽  
Vol 21 (3) ◽  
pp. 157-165 ◽  
Author(s):  
Carola Seifart ◽  
Alexandra Plagens ◽  
Astrid Dempfle ◽  
Ursula Clostermann ◽  
Claus Vogelmeier ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Inflammatory Responses ◽  
Cancer Susceptibility ◽  
Population Control ◽  
Matched Pair ◽  
German Population ◽  
Matched Pair Analysis ◽  
Genotype Frequencies ◽  
Tnf Α ◽  
Study Population

Apart from cigarette smoking, genetic factors seem to be of importance in the development of lung cancer. The present case-control study investigated frequencies of five inflammatory response gene polymorphisms (TNF-α-308, TNF-β-Intron1-252, IL-6-174, IL-10-819 and IL-10-1082) in patients with lung cancer and controls. The study population consisted of 117 patients with lung cancer (77 patients with NSCLC, including 40 Squamous Cell Carcinoma and 26 Adenocarcinoma, and 40 patients with SCLC), 117 matched controls without pulmonary disease and 243 healthy individuals (population control). Genotype analyses revealed no difference in genotype frequencies using matched-pair analysis. However, in comparison to the population control, the IL-10-1082 genotypes carrying the G allele appeared with higher frequency in the SCLC group (p= 0.006) [SCLC: 84.6%, population controls: 64.6%]. This yields an odds ratio of 3.01 for SCLC (95% CI = [1.21, 7.48]). No associations were seen for all other polymorphisms analysed. The study raises the possibility of a correlation between the IL-10-1082_G allele and the presence of SCLC in a German population. The functional IL-10-1082 polymorphism correlates with altered IL-10 levels and might influence lung cancer susceptibility by altered inflammatory responses in the airways.

scholarly journals Molecular evolution of the hyaluronan synthase 2 gene in mammals: implications for adaptations to the subterranean niche and cancer resistance

2015 ◽  
Vol 11 (5) ◽  
pp. 20150185 ◽  
Author(s):  
Christopher G. Faulkes ◽  
Kalina T. J. Davies ◽  
Stephen J. Rossiter ◽  
Nigel C. Bennett
Keyword(s):  
Purifying Selection ◽  
High Molecular Mass ◽  
Hyaluronan Synthase ◽  
Cancer Resistance ◽  
Closely Related Species ◽  
Heterocephalus Glaber ◽  
Mole Rat ◽  
Naked Mole Rat ◽  
Subterranean Mammals ◽  
Hyaluronan Synthase 2

The naked mole-rat (NMR) Heterocephalus glaber is a unique and fascinating mammal exhibiting many unusual adaptations to a subterranean lifestyle. The recent discovery of their resistance to cancer and exceptional longevity has opened up new and important avenues of research. Part of this resistance to cancer has been attributed to the fact that NMRs produce a modified form of hyaluronan—a key constituent of the extracellular matrix—that is thought to confer increased elasticity of the skin as an adaptation for living in narrow tunnels. This so-called high molecular mass hyaluronan (HMM-HA) stems from two apparently unique substitutions in the hyaluronan synthase 2 enzyme (HAS2). To test whether other subterranean mammals with similar selection pressures also show molecular adaptation in their HAS2 gene, we sequenced the HAS2 gene for 11 subterranean mammals and closely related species, and combined these with data from 57 other mammals. Comparative screening revealed that one of the two putatively important HAS2 substitutions in the NMR predicted to have a significant effect on hyaluronan synthase function was uniquely shared by all African mole-rats. Interestingly, we also identified multiple other amino acid substitutions in key domains of the HAS2 molecule, although the biological consequences of these for hyaluronan synthesis remain to be determined. Despite these results, we found evidence of strong purifying selection acting on the HAS2 gene across all mammals, and the NMR remains unique in its particular HAS2 sequence. Our results indicate that more work is needed to determine whether the apparent cancer resistance seen in NMR is shared by other members of the African mole-rat clade.

scholarly journals Population genomics of Mycobacterium tuberculosis in the Inuit

2015 ◽  
Vol 112 (44) ◽  
pp. 13609-13614 ◽  
Author(s):  
Robyn S. Lee ◽  
Nicolas Radomski ◽  
Jean-Francois Proulx ◽  
Ines Levade ◽  
B. Jesse Shapiro ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Mycobacterium Tuberculosis ◽  
Population Genomics ◽  
Purifying Selection ◽  
Synonymous Substitution ◽  
Nonsynonymous Snps ◽  
Recent Common Ancestor ◽  
Nucleotide Polymorphisms ◽  
Most Recent Common Ancestor ◽  
Bacterial Genetic

Nunavik, Québec suffers from epidemic tuberculosis (TB), with an incidence 50-fold higher than the Canadian average. Molecular studies in this region have documented limited bacterial genetic diversity among Mycobacterium tuberculosis isolates, consistent with a founder strain and/or ongoing spread. We have used whole-genome sequencing on 163 M. tuberculosis isolates from 11 geographically isolated villages to provide a high-resolution portrait of bacterial genetic diversity in this setting. All isolates were lineage 4 (Euro-American), with two sublineages present (major, n = 153; minor, n = 10). Among major sublineage isolates, there was a median of 46 pairwise single-nucleotide polymorphisms (SNPs), and the most recent common ancestor (MRCA) was in the early 20th century. Pairs of isolates within a village had significantly fewer SNPs than pairs from different villages (median: 6 vs. 47, P < 0.00005), indicating that most transmission occurs within villages. There was an excess of nonsynonymous SNPs after the diversification of M. tuberculosis within Nunavik: The ratio of nonsynonymous to synonymous substitution rates (dN/dS) was 0.534 before the MRCA but 0.777 subsequently (P = 0.010). Nonsynonymous SNPs were detected across all gene categories, arguing against positive selection and toward genetic drift with relaxation of purifying selection. Supporting the latter possibility, 28 genes were partially or completely deleted since the MRCA, including genes previously reported to be essential for M. tuberculosis growth. Our findings indicate that the epidemiologic success of M. tuberculosis in this region is more likely due to an environment conducive to TB transmission than a particularly well-adapted strain.

scholarly journals Molecular Traits and Functional Analysis of the CLAVATA3/Endosperm Surrounding Region-Related Small Signaling Peptides in Three Species of Gossypium Genus

2021 ◽  
Vol 12 ◽  
Author(s):  
Huan Lin ◽  
Wei Wang ◽  
Xiugui Chen ◽  
Zhenting Sun ◽  
Xiulan Han ◽  
...  
Keyword(s):  
Structure Prediction ◽  
Growth And Development ◽  
Developmental Stages ◽  
Evolutionary Process ◽  
Interaction Network ◽  
Purifying Selection ◽  
Regulatory Elements ◽  
Signal Molecules ◽  
Segmental Duplications ◽  
Multiple Sequence

The CLAVATA3/endosperm surrounding region-related (CLE) small peptides are a group of C-terminally encoded and post-translationally modified signal molecules involved in regulating the growth and development of various plants. However, the function and evolution of these peptides have so far remained elusive in cotton. In this study, 55, 56, and 86 CLE genes were identified in the Gossypium raimondii, Gossypium arboreum, and Gossypium hirsutum genomes, respectively, and all members were divided into seven groups. These groups were distinctly different in their protein characteristics, gene structures, conserved motifs, and multiple sequence alignment. Whole genome or segmental duplications played a significant role in the expansion of the CLE family in cotton, and experienced purifying selection during the long evolutionary process in cotton. Cis-acting regulatory elements and transcript profiling revealed that the CLE genes of cotton exist in different tissues, developmental stages, and respond to abiotic stresses. Protein properties, structure prediction, protein interaction network prediction of GhCLE2, GhCLE33.2, and GhCLE28.1 peptides were, respectively, analyzed. In addition, the overexpression of GhCLE2, GhCLE33.2, or GhCLE28.1 in Arabidopsis, respectively, resulted in a distinctive shrub-like dwarf plant, slightly purple leaves, large rosettes with large malformed leaves, and lack of reproductive growth. This study provides important insights into the evolution of cotton CLEs and delineates the functional conservatism and divergence of CLE genes in the growth and development of cotton.

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