Parallel independent losses of g-type lysozyme genes in hairless aquatic mammals

Abstract Lysozyme enzymes provide classic examples of molecular adaptation and parallel evolution, however, nearly all insights to date come from c-type lysozymes. G-type lysozymes occur in diverse vertebrates, with multiple independent duplications reported. Most mammals possess two g-type lysozyme genes (Lyg1 and Lyg2), the result of an early duplication, although some lineages are known to have subsequently lost one copy. Here we examine g-type lysozyme evolution across > 250 mammals, and reveal widespread losses of either Lyg1 or Lyg2 in several divergent taxa across the mammal tree of life. At the same time, we report strong evidence of extensive losses of both gene copies in cetaceans and sirenians, with an additional putative case of parallel loss in the tarsier. To validate these findings, we inspected published short-read data and confirmed the presence of loss of function mutations. Despite these losses, comparisons of selection pressures between intact g- and c-type lysozyme genes showed stronger purifying selection in the former, indicative of conserved function. Although the reasons for the evolutionary loss of g-type lysozymes in fully aquatic mammals is not known, we suggest that this is likely to at least partially relate to their hairlessness. Indeed, while Lyg1 does not show tissue-specific expression, recent studies have linked Lyg2 expression to anagen hair follicle development and hair loss. Such a role for g-type lysozyme would explain why the Lyg2 gene became obsolete when these taxa lost their body hair.

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Gene expression shapes the patterns of parallel evolution of herbicide resistance in the agricultural weedMonochoria vaginalis

10.1101/2021.03.10.434542 ◽

2021 ◽

Author(s):

Shinji Tanigaki ◽

Akira Uchino ◽

Shigenori Okawa ◽

Chikako Miura ◽

Kenshiro Hamamura ◽

...

Keyword(s):

Gene Expression ◽

Herbicide Resistance ◽

Parallel Evolution ◽

Acetolactate Synthase ◽

Duplicate Gene ◽

Target Site ◽

Loss Of Function ◽

Functional Characterisation ◽

Gene Copies ◽

Key Factor

AbstractThe evolution of herbicide resistance in weeds is an example of parallel evolution, through which genes encoding herbicide target proteins are repeatedly represented as evolutionary loci. The number of herbicide target-site genes differs among species, and little is known regarding the effects of duplicate gene copies on the evolution of herbicide resistance. We investigated the evolution of herbicide resistance inMonochoria vaginalis, which carries five copies of sulfonylurea target-site acetolactate synthase (ALS) genes. Suspected resistant populations collected across Japan were investigated for herbicide sensitivity andALSgene sequences, followed by functional characterisation andALSgene expression analysis. We identified over 60 resistant populations, all of which carried resistance-conferring amino acid substitutions exclusively inMvALS1orMvALS3. AllMvALS4alleles carried a loss-of-function mutation. Although the enzymatic properties of ALS encoded by these genes were not markedly different, the expression ofMvALS1andMvALS3was prominently higher among allALSgenes. The higher expression ofMvALS1andMvALS3is the driving force of the biased representation of genes during the evolution of herbicide resistance inM. vaginalis. Our findings highlight that gene expression is a key factor in creating evolutionary hotspots.

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Notch signaling coordinates ommatidial rotation in the Drosophila eye via transcriptional regulation of the EGF-Receptor ligand Argos

Scientific Reports ◽

10.1038/s41598-019-55203-w ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Yildiz Koca ◽

Benjamin E. Housden ◽

William J. Gault ◽

Sarah J. Bray ◽

Marek Mlodzik

Keyword(s):

Notch Signaling ◽

Cell Fate ◽

Planar Cell Polarity ◽

Egf Receptor ◽

Control Cell ◽

Loss Of Function ◽

Egfr Signaling ◽

Specific Expression ◽

Egfr Signaling Pathway ◽

Ommatidial Rotation

AbstractIn all metazoans, a small number of evolutionarily conserved signaling pathways are reiteratively used during development to orchestrate critical patterning and morphogenetic processes. Among these, Notch (N) signaling is essential for most aspects of tissue patterning where it mediates the communication between adjacent cells to control cell fate specification. In Drosophila, Notch signaling is required for several features of eye development, including the R3/R4 cell fate choice and R7 specification. Here we show that hypomorphic alleles of Notch, belonging to the Nfacet class, reveal a novel phenotype: while photoreceptor specification in the mutant ommatidia is largely normal, defects are observed in ommatidial rotation (OR), a planar cell polarity (PCP)-mediated cell motility process. We demonstrate that during OR Notch signaling is specifically required in the R4 photoreceptor to upregulate the transcription of argos (aos), an inhibitory ligand to the epidermal growth factor receptor (EGFR), to fine-tune the activity of EGFR signaling. Consistently, the loss-of-function defects of Nfacet alleles and EGFR-signaling pathway mutants are largely indistinguishable. A Notch-regulated aos enhancer confers R4 specific expression arguing that aos is directly regulated by Notch signaling in this context via Su(H)-Mam-dependent transcription.

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Landscape and evolution of cis- and trans-regulatory divergence in chicken genome between two contrasted breeds analyzed in three tissues at one day age

10.21203/rs.2.10726/v2 ◽

2019 ◽

Author(s):

Qiong Wang ◽

Yaxiong Jia ◽

Yuan Wang ◽

Zhihua Jiang ◽

Xiang Zhou ◽

...

Keyword(s):

Chicken Genome ◽

Reproductive Traits ◽

Purifying Selection ◽

Population Divergence ◽

Specific Reference ◽

Specific Expression ◽

Allele Specific Expression ◽

Allele Specific ◽

Trans Regulation ◽

Cis And Trans

Abstract Background: Gene expression variation is an important mechanism underlying phenotypic variation, and can occur via cis- and trans-regulation. In order to understand the role of cis- and trans-regulatory variation on population divergence of chicken, we developed reciprocal crosses of two chicken breeds, White Leghorn and Cornish Game, with major differences in body size and reproductive traits, and used them to identify the degree of cis versus trans variation in brain, liver and muscle of both male and female samples at 1 day age. Results: We provided a landscape about how the transcriptomes are regulated in the hybrid progenies of two contrasted breeds by allele specific expression analysis. Our results showed that compared with the cis-regulatory divergence, trans-acted genes existed more extensively in the chicken genome. Furthermore, a widespread tendency of compensatory regulation exists in chicken genome. Most importantly, we found the evidence of stronger purifying selection on genes regulated by trans variations than the cis elements. Conclusions: We demonstrated a pipeline to explore the allele-specific expression in the hybrid progenies of inbred lines without specific reference genome. Our research performed the first study to describe the regulatory divergence between two contrasted breeds. The results suggested that artificial selection associated with domestication in chicken may have more often acted on trans-regulatory divergence than cis.

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Auxin methylation is required for differential growth inArabidopsis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1806565115 ◽

2018 ◽

Vol 115 (26) ◽

pp. 6864-6869 ◽

Cited By ~ 10

Author(s):

Mohamad Abbas ◽

Jorge Hernández-García ◽

Stephan Pollmann ◽

Sophia L. Samodelov ◽

Martina Kolb ◽

...

Keyword(s):

Gene Expression ◽

Auxin Transport ◽

Polar Auxin Transport ◽

Asymmetric Distribution ◽

Loss Of Function ◽

Differential Growth ◽

Specific Expression ◽

Auxin Homeostasis ◽

Auxin Distribution ◽

Gene Expression Levels

Asymmetric auxin distribution is instrumental for the differential growth that causes organ bending on tropic stimuli and curvatures during plant development. Local differences in auxin concentrations are achieved mainly by polarized cellular distribution of PIN auxin transporters, but whether other mechanisms involving auxin homeostasis are also relevant for the formation of auxin gradients is not clear. Here we show that auxin methylation is required for asymmetric auxin distribution across the hypocotyl, particularly during its response to gravity. We found that loss-of-function mutants inArabidopsis IAA CARBOXYL METHYLTRANSFERASE1(IAMT1) prematurely unfold the apical hook, and that their hypocotyls are impaired in gravitropic reorientation. This defect is linked to an auxin-dependent increase inPINgene expression, leading to an increased polar auxin transport and lack of asymmetric distribution of PIN3 in theiamt1mutant. Gravitropic reorientation in theiamt1mutant could be restored with either endodermis-specific expression ofIAMT1or partial inhibition of polar auxin transport, which also results in normalPINgene expression levels. We propose that IAA methylation is necessary in gravity-sensing cells to restrict polar auxin transport within the range of auxin levels that allow for differential responses.

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Perspectives on Allele-Specific Expression

Annual Review of Biomedical Data Science ◽

10.1146/annurev-biodatasci-021621-122219 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Siobhan Cleary ◽

Cathal Seoighe

Keyword(s):

Gene Expression ◽

Genetic Variants ◽

Data Science ◽

Genetic Diseases ◽

Annual Review ◽

Publication Date ◽

Biomedical Data ◽

Specific Expression ◽

Cis Acting ◽

Gene Copies

Diploidy has profound implications for population genetics and susceptibility to genetic diseases. Although two copies are present for most genes in the human genome, they are not necessarily both active or active at the same level in a given individual. Genomic imprinting, resulting in exclusive or biased expression in favor of the allele of paternal or maternal origin, is now believed to affect hundreds of human genes. A far greater number of genes display unequal expression of gene copies due to cis-acting genetic variants that perturb gene expression. The availability of data generated by RNA sequencing applied to large numbers of individuals and tissue types has generated unprecedented opportunities to assess the contribution of genetic variation to allelic imbalance in gene expression. Here we review the insights gained through the analysis of these data about the extent of the genetic contribution to allelic expression imbalance, the tools and statistical models for gene expression imbalance, and what the results obtained reveal about the contribution of genetic variants that alter gene expression to complex human diseases and phenotypes. Expected final online publication date for the Annual Review of Biomedical Data Science, Volume 4 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Abstract 91: Genome-wide Identification and Characterization of Cardiac Hypertrophy-related Long Noncoding RNAs in Mice

Circulation Research ◽

10.1161/res.119.suppl_1.91 ◽

2016 ◽

Vol 119 (suppl_1) ◽

Author(s):

Zhanpeng Huang ◽

Gengze Wu ◽

Jian-Hua Yang ◽

Jian Ding ◽

Jinghai Chen ◽

...

Keyword(s):

Cardiac Hypertrophy ◽

Target Genes ◽

Troponin T ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Functional Screening ◽

Loss Of Function ◽

Specific Expression ◽

Functional Conservation ◽

Virus Serotype

Long noncoding RNAs (LncRNAs) are RNA transcripts longer than 200 nucleotides that lack protein-coding potential. Although thousands of lncRNAs have been identified, only a few have been linked to cardiac gene expression and function. In this study, we identified, from genome-scale RNA-seq data, 12 candidate lncRNAs associated with cardiac hypertrophy (CH-lncRNAs). The expression of these lncRNAs was altered in mouse models of cardiac hypertrophy induced by transverse aortic constriction (TAC)- or CnA transgene. To determine the function of these lncRNAs, we developed an adeno-associated virus serotype 9 (AAV9)-based functional screening in postnatal mice. An AAV9:cTNT vector, in which the cardiac troponin T (cTNT) promoter was used to direct cardiac-specific expression of target genes, was utilized to overexpress or knockdown candidate lncRNAs in mouse hearts. Postnatal day 1 wild type or CnA transgenic pups were injected with AAV9 viruses and cardiac function was measured one and two months later. Thus far, we have tested 15 candidate lncRNAs for both gain- and loss-of-function studies. Among them, two lncRNAs were demonstrated regulating hypertrophy growth when knocked down. Finally, we identified the human homologues of CH-lncRNA through analyzing the conservation of the promoter regions of lncRNA genes. We showed that the expression of these human CH-lncRNA was dysregulated in human diseased hearts, suggesting the functional conservation of these lncRNAs in cardiac disease. Our study therefore demonstrated that lncRNAs are important regulator of cardiac hypertrophy and disease.

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The Role of Discoidin Domain Receptor 2 in Tooth Development

Journal of Dental Research ◽

10.1177/0022034519892563 ◽

2019 ◽

Vol 99 (2) ◽

pp. 214-222

Author(s):

F.F. Mohamed ◽

C. Ge ◽

A. Binrayes ◽

R.T. Franceschi

Keyword(s):

Expression Pattern ◽

Alveolar Bone ◽

Tooth Development ◽

Tyrosine Kinase Receptor ◽

Loss Of Function ◽

Wild Type ◽

Specific Expression ◽

Tooth Formation ◽

Discoidin Domain Receptor ◽

Discoidin Domain Receptor 2

Collagen signaling is critical for proper bone and tooth formation. Discoidin domain receptor 2 (DDR2) is a collagen-activated tyrosine kinase receptor shown to be essential for skeletal development. Patients with loss of function mutations in DDR2 develop spondylo-meta-epiphyseal dysplasia (SMED), a rare, autosomal recessive disorder characterized by short stature, short limbs, and craniofacial anomalies. A similar phenotype was observed in Ddr2-deficient mice, which exhibit dwarfism and defective bone formation in the axial, appendicular, and cranial skeletons. However, it is not known if Ddr2 has a role in tooth formation. We first defined the expression pattern of Ddr2 during tooth formation using Ddr2-LacZ knock-in mice. Ddr2 expression was detected in the dental follicle/sac and dental papilla mesenchyme of developing teeth and in odontoblasts and the periodontal ligament (PDL) of adults. No LacZ staining was detected in wild-type littermates. This Ddr2 expression pattern suggests a potential role in the tooth and surrounding periodontium. To uncover the function of Ddr2, we used Ddr2 slie/slie mice, which contain a spontaneous 150-kb deletion in the Ddr2 locus to produce an effective null. In comparison with wild-type littermates, Ddr2 slie/slie mice displayed disproportional tooth size (decreased root/crown ratio), delayed tooth root development, widened PDL space, and interradicular alveolar bone defects. Ddr2 slie/slie mice also had abnormal collagen content associated with upregulation of periostin levels within the PDL. The delayed root formation and periodontal abnormalities may be related to defects in RUNX2-dependent differentiation of odontoblasts and osteoblasts; RUNX2-S319-P was reduced in PDLs from Ddr2 slie/slie mice, and deletion of Ddr2 in primary cell cultures from dental pulp and PDL inhibited differentiation of cells to odontoblasts or osteoblasts, respectively. Together, our studies demonstrate odontoblast- and PDL-specific expression of Ddr2 in mature and immature teeth, as well as indicate that DDR2 signaling is important for normal tooth formation and maintenance of the surrounding periodontium.

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Evolution of cis- and trans-regulatory divergence in the chicken genome between two contrasting breeds analyzed using three tissue types at one-day-old

BMC Genomics ◽

10.1186/s12864-019-6342-5 ◽

2019 ◽

Vol 20 (1) ◽

Author(s):

Qiong Wang ◽

Yaxiong Jia ◽

Yuan Wang ◽

Zhihua Jiang ◽

Xiang Zhou ◽

...

Keyword(s):

Chicken Genome ◽

Reproductive Traits ◽

Purifying Selection ◽

Population Divergence ◽

Specific Reference ◽

Specific Expression ◽

Allele Specific Expression ◽

Allele Specific ◽

Trans Regulation ◽

Cis And Trans

Abstract Background Gene expression variation is a key underlying factor influencing phenotypic variation, and can occur via cis- or trans-regulation. To understand the role of cis- and trans-regulatory variation on population divergence in chicken, we developed reciprocal crosses of two chicken breeds, White Leghorn and Cornish Game, which exhibit major differences in body size and reproductive traits, and used them to determine the degree of cis versus trans variation in the brain, liver, and muscle tissue of male and female 1-day-old specimens. Results We provided an overview of how transcriptomes are regulated in hybrid progenies of two contrasting breeds based on allele specific expression analysis. Compared with cis-regulatory divergence, trans-acting genes were more extensive in the chicken genome. In addition, considerable compensatory cis- and trans-regulatory changes exist in the chicken genome. Most importantly, stronger purifying selection was observed on genes regulated by trans-variations than in genes regulated by the cis elements. Conclusions We present a pipeline to explore allele-specific expression in hybrid progenies of inbred lines without a specific reference genome. Our research is the first study to describe the regulatory divergence between two contrasting breeds. The results suggest that artificial selection associated with domestication in chicken could have acted more on trans-regulatory divergence than on cis-regulatory divergence.

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Genome-Wide Analysis of Multiple Organellar RNA Editing Factor Family in Poplar Reveals Evolution and Roles in Drought Stress

International Journal of Molecular Sciences ◽

10.3390/ijms20061425 ◽

2019 ◽

Vol 20 (6) ◽

pp. 1425 ◽

Cited By ~ 1

Author(s):

Dongli Wang ◽

Sen Meng ◽

Wanlong Su ◽

Yu Bao ◽

Yingying Lu ◽

...

Keyword(s):

Drought Stress ◽

Rna Editing ◽

Functional Divergence ◽

Expression Patterns ◽

Purifying Selection ◽

Structural Features ◽

Specific Expression ◽

Poplar Genome ◽

Physiological Processes ◽

Genome Wide

Poplar (Populus) is one of the most important woody plants worldwide. Drought, a primary abiotic stress, seriously affects poplar growth and development. Multiple organellar RNA editing factor (MORF) genes—pivotal factors in the RNA editosome in Arabidopsis thaliana—are indispensable for the regulation of various physiological processes, including organelle C-to-U RNA editing and plasmid development, as well as in the response to stresses. Although the poplar genome sequence has been released, little is known about MORF genes in poplar, especially those involved in the response to drought stress at the genome-wide level. In this study, we identified nine MORF genes in the Populus genome. Based on the structural features of MORF proteins and the topology of the phylogenetic tree, the P. trichocarpa (Ptr) MORF family members were classified into six groups (Groups I–VI). A microsynteny analysis indicated that two (22.2%) PtrMORF genes were tandemly duplicated and seven genes (77.8%) were segmentally duplicated. Based on the dN/dS ratios, purifying selection likely played a major role in the evolution of this family and contributed to functional divergence among PtrMORF genes. Moreover, analysis of qRT-PCR data revealed that PtrMORFs exhibited tissue- and treatment-specific expression patterns. PtrMORF genes in all group were involved in the stress response. These results provide a solid foundation for further analyses of the functions and molecular evolution of MORF genes in poplar, and, in particular, for improving the drought resistance of poplar by genetics manipulation.

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Concerted evolution of human amylase genes.

Molecular and Cellular Biology ◽

10.1128/mcb.8.3.1197 ◽

1988 ◽

Vol 8 (3) ◽

pp. 1197-1205 ◽

Cited By ~ 65

Author(s):

D L Gumucio ◽

K Wiebauer ◽

R M Caldwell ◽

L C Samuelson ◽

M H Meisler

Keyword(s):

Pancreatic Amylase ◽

Amylase Gene ◽

Salivary Amylase ◽

Specific Expression ◽

Enhancer Element ◽

Tissue Specific ◽

Tissue Specific Expression ◽

Gene Copies ◽

Amylase Genes ◽

Sequence Elements

Cosmid clones containing 250 kilobases of genomic DNA from the human amylase gene cluster have been isolated. These clones contain seven distinct amylase genes which appear to comprise the complete multigene family. By sequence comparison with the cDNAs, we have identified two pancreatic amylase genes and three salivary amylase genes. Two truncated pseudogenes were also recovered. Intergenic distances of 17 to 22 kilobases separate the amylase gene copies. Within the past 10 million years, duplications, gene conversions, and unequal crossover events have resulted in a very high level of sequence similarity among human amylase gene copies. To identify sequence elements involved in tissue-specific expression and hormonal regulation, the promoter regions of the human amylase genes were sequenced and compared with those of the corresponding mouse genes. The promoters of the human and mouse pancreatic amylase genes are highly homologous between nucleotide -160 and the cap site. Two sequence elements thought to influence pancreas-specific expression of the rodent genes are present in the human genes. In contrast, similarity in the 5' flanking sequences of the salivary amylase genes is limited to several short sequence elements whose positions and orientations differ in the two species. Some of these sequence elements are also associated with other parotid-specific genes and may be involved in their tissue-specific expression. A glucocorticoid response element and a general enhancer element are closely associated in several of the amylase promoters.

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