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1.
Genes (Basel) ; 15(2)2024 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-38397219

RESUMO

Quercus is a valuable genus ecologically, economically, and culturally. They are keystone species in many ecosystems. Species delimitation and phylogenetic studies of this genus are difficult owing to frequent hybridization. With an increasing number of genetic resources, we will gain a deeper understanding of this genus. In the present study, we collected four Quercus section Cyclobalanopsis species (Q. poilanei, Q. helferiana, Q. camusiae, and Q. semiserrata) distributed in Southeast Asia and sequenced their complete genomes. Following analysis, we compared the results with those of other species in the genus Quercus. These four chloroplast genomes ranged from 160,784 bp (Q. poilanei) to 161,632 bp (Q. camusiae) in length, with an overall guanine and cytosine (GC) content of 36.9%. Their chloroplast genomic organization and order, as well as their GC content, were similar to those of other Quercus species. We identified seven regions with relatively high variability (rps16, ndhk, accD, ycf1, psbZ-trnG-GCC, rbcL-accD, and rpl32-trnL-UAG) which could potentially serve as plastid markers for further taxonomic and phylogenetic studies within Quercus. Our phylogenetic tree supported the idea that the genus Quercus forms two well-differentiated lineages (corresponding to the subgenera Quercus and Cerris). Of the three sections in the subgenus Cerris, the section Ilex was split into two clusters, each nested in the other two sections. Moreover, Q. camusiae and Q. semiserrata detected in this study diverged first in the section Cyclobalanopsis and mixed with Q. engleriana in the section Ilex. In particular, 11 protein coding genes (atpF, ndhA, ndhD, ndhF, ndhK, petB, petD, rbcL, rpl22, ycf1, and ycf3) were subjected to positive selection pressure. Overall, this study enriches the chloroplast genome resources of Quercus, which will facilitate further analyses of phylogenetic relationships in this ecologically important tree genus.


Assuntos
Genoma de Cloroplastos , Quercus , Filogenia , Quercus/genética , Ecossistema , Genômica
2.
Bioessays ; 46(4): e2300201, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38351661

RESUMO

The human genome project's lasting legacies are the emerging insights into human physiology and disease, and the ascendance of biology as the dominant science of the 21st century. Sequencing revealed that >90% of the human genome is not coding for proteins, as originally thought, but rather is overwhelmingly transcribed into non-protein coding, or non-coding, RNAs (ncRNAs). This discovery initially led to the hypothesis that most genomic DNA is "junk", a term still championed by some geneticists and evolutionary biologists. In contrast, molecular biologists and biochemists studying the vast number of transcripts produced from most of this genome "junk" often surmise that these ncRNAs have biological significance. What gives? This essay contrasts the two opposing, extant viewpoints, aiming to explain their bases, which arise from distinct reference frames of the underlying scientific disciplines. Finally, it aims to reconcile these divergent mindsets in hopes of stimulating synergy between scientific fields.


Assuntos
Genoma Humano , RNA não Traduzido , Humanos , RNA não Traduzido/genética , Proteínas/genética
3.
Clin Transl Med ; 14(1): e1523, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38193640

RESUMO

BACKGROUND: Epithelial ovarian cancer (EOC) heavily relies on oxidative phosphorylation (OXPHOS) and exhibits distinct mitochondrial metabolic reprogramming. Up to now, the evolutionary pattern of somatic mitochondrial DNA (mtDNA) mutations in EOC tissues and their potential roles in metabolic remodelling have not been systematically elucidated. METHODS: Based on a large somatic mtDNA mutation dataset from private and public EOC cohorts (239 and 118 patients, respectively), we most comprehensively characterised the EOC-specific evolutionary pattern of mtDNA mutations and investigated its biological implication. RESULTS: Mutational profiling revealed that the mitochondrial genome of EOC tissues was highly unstable compared with non-cancerous ovary tissues. Furthermore, our data indicated the delayed heteroplasmy accumulation of mtDNA control region (mtCTR) mutations and near-complete absence of mtCTR non-hypervariable segment (non-HVS) mutations in EOC tissues, which is consistent with stringent negative selection against mtCTR mutation. Additionally, we observed a bidirectional and region-specific evolutionary pattern of mtDNA coding region mutations, manifested as significant negative selection against mutations in complex V (ATP6/ATP8) and tRNA loop regions, and potential positive selection on mutations in complex III (MT-CYB). Meanwhile, EOC tissues showed higher mitochondrial biogenesis compared with non-cancerous ovary tissues. Further analysis revealed the significant association between mtDNA mutations and both mitochondrial biogenesis and overall survival of EOC patients. CONCLUSIONS: Our study presents a comprehensive delineation of EOC-specific evolutionary patterns of mtDNA mutations that aligned well with the specific mitochondrial metabolic remodelling, conferring novel insights into the functional roles of mtDNA mutations in EOC tumourigenesis and progression.


Assuntos
DNA Mitocondrial , Neoplasias Ovarianas , Feminino , Humanos , DNA Mitocondrial/genética , Carcinoma Epitelial do Ovário/genética , Mutação/genética , Neoplasias Ovarianas/genética , Estresse Oxidativo
4.
Planta ; 259(2): 45, 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38281265

RESUMO

MAIN CONCLUSION: The divergence of subsect. Gerardianae was likely triggered by the uplift of the Qinghai-Tibetan Plateau and adjacent mountains. Pinus bungeana might have probably experienced expansion since Last Interglacial period. Historical geological and climatic oscillations have profoundly affected patterns of nucleotide variability, evolutionary history, and species divergence in numerous plants of the Northern Hemisphere. However, how long-lived conifers responded to geological and climatic fluctuations in East Asia remain poorly understood. Here, based on paternally inherited chloroplast genomes and maternally inherited mitochondrial DNA markers, we investigated the population demographic history and molecular evolution of subsect. Gerardianae (only including three species, Pinus bungeana, P. gerardiana, and P. squamata) of Pinus. A low level of nucleotide diversity was found in P. bungeana (π was 0.00016 in chloroplast DNA sequences, and 0.00304 in mitochondrial DNAs). The haplotype-based phylogenetic topology and unimodal distributions of demographic analysis suggested that P. bungeana probably originated in the southern Qinling Mountains and experienced rapid population expansion since Last Interglacial period. Phylogenetic analysis revealed that P. gerardiana and P. squamata had closer genetic relationship. The species divergence of subsect. Gerardianae occurred about 27.18 million years ago (Mya) during the middle to late Oligocene, which was significantly associated with the uplift of the Qinghai-Tibetan Plateau and adjacent mountains from the Eocene to the mid-Pliocene. The molecular evolutionary analysis showed that two chloroplast genes (psaI and ycf1) were under positive selection, the genetic lineages of P. bungeana exhibited higher transition and nonsynonymous mutations, which were involved with the strongly environmental adaptation. These findings shed light on the population evolutionary history of white pine species and provide striking insights for comprehension of their species divergence and molecular evolution.


Assuntos
Genoma de Cloroplastos , Pinus , Filogenia , Pinus/genética , Genoma de Cloroplastos/genética , Evolução Molecular , DNA de Cloroplastos/genética , DNA Mitocondrial/genética , Nucleotídeos , Demografia , Variação Genética
5.
Mitochondrial DNA B Resour ; 8(6): 643-647, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37312972

RESUMO

Gypsophila huashanensis Y. W. Tsui & D. Q. Lu (Caryophyllaceae) is an endemic herb species to the Qinling Mountains in China. In this study, we characterized its whole plastid genome using the Illumina sequencing platform. The complete plastid genome of G. huashanensis is 152,457 bp in length, including a large single-copy DNA region of 83,476 bp, a small single-copy DNA region of 17,345 bp, and a pair of inverted repeat DNA sequences of 25,818 bp. The genome contains 130 genes comprising 85 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Evolutionary analysis showed that the non-coding regions of Caryophyllaceae exhibit a higher level of divergence than the exon regions. Gene site selection analysis suggested that 11 coding protein genes (accD, atpF, ndhA, ndhB, petB, petD, rpoCl, rpoC2, rps16, ycfl, and ycf2) have some sites under protein sequence evolution. Phylogenetic analysis showed that G. huashanensis is most closely related to the congeneric species G. oldhamiana. These results are very useful for studying phylogenetic evolution and species divergence in the family Caryophyllaceae.

6.
Theranostics ; 13(1): 324-338, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36593960

RESUMO

Rationale: Mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) mutations and subsequent metabolic defects are closely involved in tumorigenesis and progression in a cancer-type specific manner. To date, the mutational pattern of mtDNA somatic mutations in colorectal cancer (CRC) tissues and its clinical implication are still not completely clear. Methods: In the present study, we generated a large mtDNA somatic mutation dataset from three CRC cohorts (432, 1,015, and 845 patients, respectively) and then most comprehensively characterized the CRC-specific evolutionary pattern and its clinical implication. Results: Our results showed that the mtDNA control region (mtCTR) with a high mutation density exhibited a distinct mutation spectrum characterizing a high enrichment of L-strand C > T mutations, which was contrary to the H-strand C > T mutational bias observed in the mtDNA coding region (mtCDR) (P < 0.001). Further analysis clearly confirmed the relaxed evolutionary selection of mtCTR mutations, which was mainly characterized by the similar distribution of hypervariable region (HVS) and non-HVS mutation density. Moreover, significant negative selection was identified in mutations of mtDNA complex V (ATP6/ATP8) and tRNA loop regions. Although our data showed that oxidative metabolism was commonly increased in CRC cells, mtDNA somatic mutations in CRC tissues were not closely associated with mitochondrial biogenesis, oxidative metabolism, and clinical progression, suggesting a cancer-type specific relationship between mtDNA mutations and mitochondrial metabolic functions in CRC cells. Conclusion: Our study identified the CRC-specific evolutionary mode of mtDNA mutations, which is possibly matched to specific mitochondrial metabolic remodeling and confers new mechanic insight into CRC tumorigenesis.


Assuntos
Neoplasias Colorretais , DNA Mitocondrial , Humanos , DNA Mitocondrial/genética , Mutação/genética , Mitocôndrias/genética , Neoplasias Colorretais/genética , Carcinogênese , Estresse Oxidativo
7.
Front Physiol ; 13: 947958, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36277196

RESUMO

Understanding Na+ uptake mechanisms in vertebrates has been a research priority since vertebrate ancestors were thought to originate from hyperosmotic marine habitats to the hypoosmotic freshwater system. Given the evolutionary success of osmoregulator teleosts, these freshwater conquerors from the marine habitats are reasonably considered to develop the traits of absorbing Na+ from the Na+-poor circumstances for ionic homeostasis. However, in teleosts, the loss of epithelial Na+ channel (ENaC) has long been a mystery and an issue under debate in the evolution of vertebrates. In this study, we evaluate the idea that energetic efficiency in teleosts may have been improved by selection for ENaC loss and an evolved energy-saving alternative, the Na+/H+ exchangers (NHE3)-mediated Na+ uptake/NH4 + excretion machinery. The present study approaches this question from the lamprey, a pioneer invader of freshwater habitats, initially developed ENaC-mediated Na+ uptake driven by energy-consuming apical H+-ATPase (VHA) in the gills, similar to amphibian skin and external gills. Later, teleosts may have intensified ammonotelism to generate larger NH4 + outward gradients that facilitate NHE3-mediated Na+ uptake against an unfavorable Na+ gradient in freshwater without consuming additional ATP. Therefore, this study provides a fresh starting point for expanding our understanding of vertebrate ion regulation and environmental adaptation within the framework of the energy constraint concept.

8.
EBioMedicine ; 80: 104058, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35594659

RESUMO

BACKGROUND: Mitochondrial DNA (mtDNA) mutations alter mitochondrial function in oxidative metabolism and play an important role in tumorigenesis. A series of studies have demonstrated that the mtDNA control region (mtCTR), which is essential for mtDNA replication and transcription, represents a mutational hotspot in human tumors. However, a comprehensive pan-cancer evolutionary pattern analysis of mtCTR mutations is urgently needed. METHODS: We generated a comprehensive combined dataset containing 10026 mtDNA somatic mutations from 4664 patients, covering 20 tumor types based on public and private next-generation sequencing data. FINDINGS: Our results demonstrated a significantly higher and much more variable mutation rate in mtCTR than in the coding region across different tumor types. Moreover, our data showed a remarkable distributional bias of tumor somatic mutations between the hypervariable segment (HVS) and non-HVS, with a significantly higher mutation density and average mutation sites in HVS. Importantly, the tumor-specific mutational pattern between mtCTR HVS and non-HVS was identified, which was classified into three evolutionary selection types (relaxed, moderate, and strict constraint types). Analysis of substitution patterns revealed that the prevalence of CH > TH in non-HVS greatly contributed to the mutational selection pattern of mtCTR across different tumor types. Furthermore, we found that the mutational pattern of mtCTR in the four tumor types was clearly associated with mitochondrial biogenesis, mitochondrial oxidative metabolism, and the overall survival of patients. INTERPRETATION: Our results suggest that somatic mutations in mtCTR may be shaped by tumor-specific selective pressure and are involved in tumorigenesis. FUNDINGS: National Natural Science Foundation of China [grants 82020108023, 81830070, 81872302], and Autonomous Project of State Key Laboratory of Cancer Biology, China [grants CBSKL2019ZZ06, CBSKL2019ZZ27].


Assuntos
DNA Mitocondrial , Neoplasias , Carcinogênese , Transformação Celular Neoplásica , Análise Mutacional de DNA , DNA Mitocondrial/genética , Humanos , Mitocôndrias/genética , Mutação , Neoplasias/genética
9.
Mol Biol Evol ; 39(2)2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-34897509

RESUMO

Long intergenic noncoding RNAs (lincRNAs) represent a large fraction of transcribed loci in eukaryotic genomes. Although classified as noncoding, most lincRNAs contain open reading frames (ORFs), and it remains unclear why cytoplasmic lincRNAs are not or very inefficiently translated. Here, we analyzed signatures of hindered translation in lincRNA sequences from five eukaryotes, covering a range of natural selection pressures. In fission yeast and Caenorhabditis elegans, that is, species under strong selection, we detected significantly shorter ORFs, a suboptimal sequence context around start codons for translation initiation, and trinucleotides ("codons") corresponding to less abundant tRNAs than for neutrally evolving control sequences, likely impeding translation elongation. For human, we detected signatures for cell-type-specific hindrance of lincRNA translation, in particular codons in abundant cytoplasmic lincRNAs corresponding to lower expressed tRNAs than control codons, in three out of five human cell lines. We verified that varying tRNA expression levels between cell lines are reflected in the amount of ribosomes bound to cytoplasmic lincRNAs in each cell line. We further propose that codons at ORF starts are particularly important for reducing ribosome-binding to cytoplasmic lincRNA ORFs. Altogether, our analyses indicate that in species under stronger selection lincRNAs evolved sequence features generally hindering translation and support cell-type-specific hindrance of translation efficiency in human lincRNAs. The sequence signatures we have identified may improve predicting peptide-coding and genuine noncoding lincRNAs in a cell type.


Assuntos
RNA Longo não Codificante , Seleção Genética , Animais , Caenorhabditis elegans/genética , Linhagem Celular , Eucariotos/genética , Humanos , Fases de Leitura Aberta , RNA Longo não Codificante/genética , RNA não Traduzido , Schizosaccharomyces/genética
10.
Evol Bioinform Online ; 17: 11769343211035140, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34366661

RESUMO

The RNA G-quadruplex (rG4) is a kind of non-canonical high-order secondary structure with important biological functions and is enriched in untranslated regions (UTRs) of protein-coding genes. However, how rG4 structures evolve is largely unknown. Here, we systematically investigated the evolution of RNA sequences around UTR rG4 structures in 5 eukaryotic organisms. We found universal selection on UTR sequences, which facilitated rG4 formation in all the organisms that we analyzed. While G-rich sequences were preferred in the rG4 structural region, C-rich sequences were selectively not preferred. The selective pressure acting on rG4 structures in the UTRs of genes with higher G content was significantly smaller. Furthermore, we found that rG4 structures experienced smaller evolutionary selection near the translation initiation region in the 5' UTR, near the polyadenylation signals in the 3' UTR, and in regions flanking the miRNA targets in the 3' UTR. These results suggest universal selection for rG4 formation in the UTRs of eukaryotic genomes and the selection may be related to the biological functions of rG4s.

11.
Genomics ; 113(4): 2365-2376, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34051325

RESUMO

The forest tree family Aceraceae is widespread in the northern hemisphere and it has ecological and economic importance. However, the phylogenetic relationships and classifications within the family are still controversial due to transitional intraspecific morphological characteristics and introgression hybridization among species. In this study, we determined the evolutionary relationships and molecular evolution of Aceraceae based on plastid phylogenomics and two nuclear gene variations. Phylogenetic analysis based on the plastid genomes suggested that Aceraceae species can be divided into two larger sub-clades corresponding to the two genera Acer and Dipteronia. Conjoint analysis of the plastid and nuclear gene sequences supported the classification with two genera in the family. Molecular dating showed that the two genera diverged 60.2 million years ago, which is generally consistently with previously reported results. Divergence hotspots and positively selected genes identified in the plastid genomes could be useful genetic resources in Aceraceae.


Assuntos
Aceraceae , Evolução Molecular , Florestas , Filogenia , Plastídeos/genética
12.
Mol Biol Evol ; 38(5): 2014-2029, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33570580

RESUMO

Mimivirus is one of the most complex and largest viruses known. The origin and evolution of Mimivirus and other giant viruses have been a subject of intense study in the last two decades. The two prevailing hypotheses on the origin of Mimivirus and other viruses are the reduction hypothesis, which posits that viruses emerged from modern unicellular organisms; whereas the virus-first hypothesis proposes viruses as relics of precellular forms of life. In this study, to gain insights into the origin of Mimivirus, we have carried out extensive phylogenetic, correlation, and multidimensional scaling analyses of the putative proteins involved in the replication of its 1.2-Mb large genome. Correlation analysis and multidimensional scaling methods were validated using bacteriophage, bacteria, archaea, and eukaryotic replication proteins before applying to Mimivirus. We show that a large fraction of mimiviral replication proteins, including polymerase B, clamp, and clamp loaders are of eukaryotic origin and are coevolving. Although phylogenetic analysis places some components along the lineages of phage and bacteria, we show that all the replication-related genes have been homogenized and are under purifying selection. Collectively our analysis supports the idea that Mimivirus originated from a complex cellular ancestor. We hypothesize that Mimivirus has largely retained complex replication machinery reminiscent of its progenitor while losing most of the other genes related to processes such as metabolism and translation.


Assuntos
Coevolução Biológica , Mimiviridae/genética , Seleção Genética , Proteínas Virais/genética , Replicação Viral/genética , Transferência Genética Horizontal , Análise de Escalonamento Multidimensional , Filogenia
13.
Plant Cell Rep ; 39(6): 765-777, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32215683

RESUMO

KEY MESSAGE: The DNA fragments transferred among cotton cytoplasmic genomes are highly differentiated. The wild D group cotton species have undergone much greater evolution compared with cultivated AD group. Cotton (Gossypium spp.) is one of the most economically important fiber crops worldwide. Gene transfer, nucleotide evolution, and the codon usage preferences in cytoplasmic genomes are important evolutionary characteristics of high plants. In this study, we analyzed the nucleotide sequence evolution, codon usage, and transfer of cytoplasmic DNA fragments in Gossypium chloroplast (cp) and mitochondrial (mt) genomes, including the A genome group, wild D group, and cultivated AD group of cotton species. Our analyses indicated that the differences in the length of transferred cytoplasmic DNA fragments were not significant in mitochondrial and chloroplast sequences. Analysis of the transfer of tRNAs found that trnQ and nine other tRNA genes were commonly transferred between two different cytoplasmic genomes. The Codon Adaptation Index values showed that Gossypium cp genomes prefer A/T-ending codons. Codon preference selection was higher in the D group than the other two groups. Nucleotide sequence evolution analysis showed that intergenic spacer sequences were more variable than coding regions and nonsynonymous mutations were clearly more common in cp genomes than mt genomes. Evolutionary analysis showed that the substitution rate was much higher in cp genomes than mt genomes. Interestingly, the D group cotton species have undergone much faster evolution compared with cultivated AD groups, possibly due to the selection and domestication of diverse cotton species. Our results demonstrate that gene transfer and differential nucleotide sequence evolution have occurred frequently in cotton cytoplasmic genomes.


Assuntos
Sequência de Bases , Evolução Molecular , Genoma de Planta , Gossypium/genética , Anticódon , Códon , Variação Genética , Genoma de Cloroplastos , Genoma Mitocondrial/genética , Polimorfismo de Nucleotídeo Único
14.
Int J Parasitol ; 50(1): 1-18, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31857072

RESUMO

Second and third generation sequencing methods are crucial for population genetic studies, and variant detection is a popular approach for exploiting this sequence data. While mini- and microsatellites are historically useful markers for studying important Protozoa such as Toxoplasma and Plasmodium spp., detecting non-repetitive variants such as those found in genes can be fundamental to investigating a pathogen's biology. These variants, namely single nucleotide polymorphisms and insertions and deletions, can help elucidate the genetic basis of an organism's pathogenicity, identify selective pressures, and resolve phylogenetic relationships. They also have the added benefit of possessing a comparatively low mutation rate, which contributes to their stability. However, there is a plethora of variant analysis tools with nuanced pipelines and conflicting recommendations for best practise, which can be confounding. This lack of standardisation means that variant analysis requires careful parameter optimisation, an understanding of its limitations, and the availability of high quality data. This review explores the value of variant detection when applied to non-model organisms such as clinically important protozoan pathogens. The limitations of current methods are discussed, including special considerations that require the end-users' attention to ensure that the results generated are reproducible, and the biological conclusions drawn are valid.


Assuntos
Biologia Computacional/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Parasitos/genética , Infecções por Protozoários/genética , Animais , DNA de Protozoário , Resistência a Medicamentos/genética , Variação Genética , Genética Populacional , Genoma de Protozoário , Humanos , Leishmania/genética , Filogenia , Plasmodium/genética , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Toxoplasma/genética , Trypanosoma cruzi/genética
15.
Genes Brain Behav ; 19(1): e12614, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31605445

RESUMO

The underlying neurological events accompanying dog domestication remain elusive. To reconstruct the domestication process in an experimental setting, silver foxes (Vulpes vulpes) have been deliberately bred for tame vs aggressive behaviors for more than 50 generations at the Institute for Cytology and Genetics in Novosibirsk, Russia. The hypothalamus is an essential part of the hypothalamic-pituitary-adrenal axis and regulates the fight-or-flight response, and thus, we hypothesized that selective breeding for tameness/aggressiveness has shaped the hypothalamic transcriptomic profile. RNA-seq analysis identified 70 differentially expressed genes (DEGs). Seven of these genes, DKKL1, FBLN7, NPL, PRIMPOL, PTGRN, SHCBP1L and SKIV2L, showed the same direction expression differences in the hypothalamus, basal forebrain and prefrontal cortex. The genes differentially expressed across the three tissues are involved in cell division, differentiation, adhesion and carbohydrate processing, suggesting an association of these processes with selective breeding. Additionally, 159 transcripts from the hypothalamus demonstrated differences in the abundance of alternative spliced forms between the tame and aggressive foxes. Weighted gene coexpression network analyses also suggested that gene modules in hypothalamus were significantly associated with tame vs aggressive behavior. Pathways associated with these modules include signal transduction, interleukin signaling, cytokine-cytokine receptor interaction and peptide ligand-binding receptors (eg, G-protein coupled receptor [GPCR] ligand binding). Current studies show the selection for tameness vs aggressiveness in foxes is associated with unique hypothalamic gene profiles partly shared with other brain regions and highlight DEGs involved in biological processes such as development, differentiation and immunological responses. The role of these processes in fox and dog domestication remains to be determined.


Assuntos
Agressão , Raposas/genética , Hipotálamo/metabolismo , Transcriptoma , Animais , Raposas/fisiologia , Redes Reguladoras de Genes
16.
Clin Microbiol Rev ; 32(4)2019 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-31366610

RESUMO

Protozoan Plasmodium parasites are the causative agents of malaria, a deadly disease that continues to afflict hundreds of millions of people every year. Infections with malaria parasites can be asymptomatic, with mild or severe symptoms, or fatal, depending on many factors such as parasite virulence and host immune status. Malaria can be treated with various drugs, with artemisinin-based combination therapies (ACTs) being the first-line choice. Recent advances in genetics and genomics of malaria parasites have contributed greatly to our understanding of parasite population dynamics, transmission, drug responses, and pathogenesis. However, knowledge gaps in parasite biology and host-parasite interactions still remain. Parasites resistant to multiple antimalarial drugs have emerged, while advanced clinical trials have shown partial efficacy for one available vaccine. Here we discuss genetic and genomic studies of Plasmodium biology, host-parasite interactions, population structures, mosquito infectivity, antigenic variation, and targets for treatment and immunization. Knowledge from these studies will advance our understanding of malaria pathogenesis, epidemiology, and evolution and will support work to discover and develop new medicines and vaccines.


Assuntos
Antimaláricos/farmacologia , Resistência a Medicamentos/genética , Evolução Molecular , Genoma de Protozoário/genética , Malária/epidemiologia , Malária/parasitologia , Plasmodium/efeitos dos fármacos , Plasmodium/genética , Humanos , Plasmodium/classificação , Plasmodium/patogenicidade
17.
Elife ; 82019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31159924

RESUMO

CHC22 clathrin plays a key role in intracellular membrane traffic of the insulin-responsive glucose transporter GLUT4 in humans. We performed population genetic and phylogenetic analyses of the CHC22-encoding CLTCL1 gene, revealing independent gene loss in at least two vertebrate lineages, after arising from gene duplication. All vertebrates retained the paralogous CLTC gene encoding CHC17 clathrin, which mediates endocytosis. For vertebrates retaining CLTCL1, strong evidence for purifying selection supports CHC22 functionality. All human populations maintained two high frequency CLTCL1 allelic variants, encoding either methionine or valine at position 1316. Functional studies indicated that CHC22-V1316, which is more frequent in farming populations than in hunter-gatherers, has different cellular dynamics than M1316-CHC22 and is less effective at controlling GLUT4 membrane traffic, altering its insulin-regulated response. These analyses suggest that ancestral human dietary change influenced selection of allotypes that affect CHC22's role in metabolism and have potential to differentially influence the human insulin response.


Assuntos
Cadeias Pesadas de Clatrina/genética , Cadeias Pesadas de Clatrina/metabolismo , Variação Genética , Glucose/metabolismo , Alelos , Dieta , Evolução Molecular , Humanos , Seleção Genética
18.
Biochem Biophys Res Commun ; 514(3): 726-733, 2019 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-31078274

RESUMO

Microsatellites (SSRs) are ubiquitous in coding and non-coding regions of the Ebolavirus genomes. We synthetically analyzed the microsatellites in whole-genome and terminal regions of 219 Ebolavirus genomes from five species. The Ebolavirus sequences were observed with small intraspecies variations and large interspecific variations, especially in the terminal non-coding regions. Only five conserved microsatellites were detected in the complete genomes, and four of them which well base-paired to help forming conserved stem-loop structures mainly appeared in the terminal non-coding regions. These results suggest that the conserved microsatellites may be evolutionary selected to form conserved secondary structures in 5', 3' terminals of Ebolavirus genomes. It may help to understand the biological significance of microsatellites in Ebolavirus and also other virus genomes.


Assuntos
Sequência Conservada , Ebolavirus/genética , Genoma Viral , Sequências Repetidas Invertidas , Repetições de Microssatélites , RNA Viral/genética , Pareamento de Bases , Bases de Dados Genéticas , Ebolavirus/classificação , Evolução Molecular , Conformação de Ácido Nucleico , RNA Viral/química , Seleção Genética , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico
19.
Int J Mol Sci ; 19(11)2018 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-30453667

RESUMO

Flowering time is a key agronomic trait, directly influencing crop yield and quality. Many flowering-time genes have been identified and characterized in the model plant Arabidopsis thaliana; however, these genes remain uncharacterized in many agronomically important Brassica crops. In this study, we identified 1064, 510, and 524 putative orthologs of A. thaliana flowering-time genes from Brassica napus, Brassica rapa, and Brassica oleracea, respectively, and found that genes involved in the aging and ambient temperature pathways were fewer than those in other flowering pathways. Flowering-time genes were distributed mostly on chromosome C03 in B. napus and B. oleracea, and on chromosome A09 in B. rapa. Calculation of non-synonymous (Ka)/synonymous substitution (Ks) ratios suggested that flowering-time genes in vernalization pathways experienced higher selection pressure than those in other pathways. Expression analysis showed that most vernalization-pathway genes were expressed in flowering organs. Approximately 40% of these genes were highly expressed in the anther, whereas flowering-time integrator genes were expressed in a highly organ-specific manner. Evolutionary selection pressures were negatively correlated with the breadth and expression levels of vernalization-pathway genes. These findings provide an integrated framework of flowering-time genes in these three Brassica crops and provide a foundation for deciphering the relationship between gene expression patterns and their evolutionary selection pressures in Brassica napus.


Assuntos
Brassica napus/genética , Flores/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Genoma de Planta , Seleção Genética , Cromossomos de Plantas/genética , Flores/fisiologia , Família Multigênica , Filogenia , Fatores de Tempo
20.
Prion ; 12(2): 83-87, 2018 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-29388474

RESUMO

Historically, the observation of naturally occurring cases of prion disease led to the classification of different susceptibility grades and to the designation of prion resistant species. However, the development of highly efficient in vitro prion propagation systems and the generation of ad hoc transgenic models allowed determining that leporidae and equidae families have been erroneously considered resistant to prion infection. On the contrary, similar approaches revealed an unexpected high level of resistance of the canidae family. In PLoS Pathogens [ 1 ], we describe experiments directed toward elucidating which are the determinants of the alleged prion resistance of this family. Studies based on the sequence of the canine prion protein coupled with structural in silico analysis identified a key residue probably implicated in this resistance. Cell and brain-based PMCA highlighted that the presence of aspartic or glutamic acid at codon 163 of the canid PrP, strongly inhibits prion replication in vitro. Transgenic animals carrying this substitution in mouse PrP were resistant to prion infection after intracerebral challenge with different mouse prion strains. The confirmation of the importance of this substitution and its exclusivity in this family, suggests it could have been evolutionarily favored, due to their diet based on carrion and small ruminants.


Assuntos
Doenças Priônicas/diagnóstico , Doenças Priônicas/metabolismo , Príons/metabolismo , Animais , Códon/genética , Cães , Evolução Molecular , Humanos , Camundongos , Proteínas Priônicas/metabolismo , Dobramento de Proteína
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