Molecular evolution of DNMT1 in vertebrates: duplications in marsupials followed by positive selection

AbstractDNA methylation is mediated by a conserved family of DNA methyltransferases (Dnmts). The human genome encodes five Dnmts: Dnmt1, Dnmt2, Dnmt3a, Dnmt3b and Dnmt3L. Despite their high degree of conservation among different species, genes encoding Dnmts have been duplicated and/or lost in multiple lineages throughout evolution, indicating that the DNA methylation machinery has some potential to undergo evolutionary change. However, little is known about the extent to which this machinery, or the methylome, varies among vertebrates. Here, we study the molecular evolution of Dnmt1, the enzyme responsible for maintenance of DNA methylation patterns after replication, in 79 vertebrate species. Our analyses show that all studied species exhibit a single copy of DNMT1, with the exception of tilapia and marsupials (tammar wallaby, koala, Tasmanian devil and opossum), each of which exhibits two apparently functional DNMT1 copies. Our phylogenetic analyses indicate that DNMT1 duplicated before the divergence of marsupials (i.e., at least ~75 million years ago), thus giving rise to two DNMT1 copies in marsupials (copy 1 and copy 2). In the opossum lineage, copy 2 was lost, and copy 1 recently duplicated again, generating three DNMT1 copies: two putatively functional genes (copy 1a and 1b) and one pseudogene (copy 1ψ). Both marsupial copies (DNMT1 copies 1 and 2) are under purifying selection, and copy 2 exhibits elevated rates of evolution and signatures of positive selection, suggesting a scenario of neofunctionalization. This gene duplication might have resulted in modifications in marsupial methylomes and their dynamics.

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Calreticulin molecular evolution: a strong purifying and episodic diversifying selection result

Biologia ◽

10.2478/s11756-013-0327-7 ◽

2014 ◽

Vol 69 (3) ◽

Cited By ~ 3

Author(s):

Rigers Bakiu

Keyword(s):

Molecular Evolution ◽

Higher Plants ◽

Phylogenetic Analyses ◽

Purifying Selection ◽

Amino Acid Sequences ◽

Over Expression ◽

Diversifying Selection ◽

Pathological Conditions ◽

Weight Protein ◽

Low Molecular Weight Protein

AbstractCalreticulin (CRT) is a low molecular weight protein present in vertebrates, invertebrates and higher plants. Its multiple functions have been demonstrated. It plays an important role as a chaperone and Ca2+ buffer inside sarcoplasmic/endoplasmic reticulum (SR/ER), and outside the ER in many physiological/pathological processes. Recently it has been observed that CRT over-expression or its absence is linked to various pathological conditions, such as malignant evolution and progression, and these facts really increased its study interests. Using an evolution approach CRT was further characterized. Several Bayesian phylogenetic analyses were performed using coding and amino acid sequences. CRT molecular evolution was investigated for the presence of negative or/and positive selection using HyPhy package. The results indicated that the purifying selection might have operated over the whole CRT primary structure. Although, an episodic diversifying selection was also found on the analyzed CRT sequences.

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Establishment and Maintenance of Genomic Methylation Patterns in Mouse Embryonic Stem Cells by Dnmt3a and Dnmt3b

Molecular and Cellular Biology ◽

10.1128/mcb.23.16.5594-5605.2003 ◽

2003 ◽

Vol 23 (16) ◽

pp. 5594-5605 ◽

Cited By ~ 473

Author(s):

Taiping Chen ◽

Yoshihide Ueda ◽

Jonathan E. Dodge ◽

Zhenjuan Wang ◽

En Li

Keyword(s):

Dna Methylation ◽

De Novo ◽

Es Cells ◽

Embryonic Stem ◽

Single Copy ◽

Dna Methyltransferases ◽

Methylation Patterns ◽

Genomic Methylation ◽

De Novo Methylation

ABSTRACT We have previously shown that the DNA methyltransferases Dnmt3a and Dnmt3b carry out de novo methylation of the mouse genome during early postimplantation development and of maternally imprinted genes in the oocyte. In the present study, we demonstrate that Dnmt3a and Dnmt3b are also essential for the stable inheritance, or “maintenance,” of DNA methylation patterns. Inactivation of both Dnmt3a and Dnmt3b in embryonic stem (ES) cells results in progressive loss of methylation in various repeats and single-copy genes. Interestingly, introduction of the Dnmt3a, Dnmt3a2, and Dnmt3b1 isoforms back into highly demethylated mutant ES cells restores genomic methylation patterns; these isoforms appear to have both common and distinct DNA targets, but they all fail to restore the maternal methylation imprints. In contrast, overexpression of Dnmt1 and Dnmt3b3 failed to restore DNA methylation patterns due to their inability to catalyze de novo methylation in vivo. We also show that hypermethylation of genomic DNA by Dnmt3a and Dnmt3b is necessary for ES cells to form teratomas in nude mice. These results indicate that genomic methylation patterns are determined partly through differential expression of different Dnmt3a and Dnmt3b isoforms.

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The DNA Methylation Landscape of Giant Viruses

10.1101/2019.12.21.884833 ◽

2019 ◽

Author(s):

Sandra Jeudy ◽

Sofia Rigou ◽

Jean-Marie Alempic ◽

Jean-Michel Claverie ◽

Chantal Abergel ◽

...

Keyword(s):

Dna Methylation ◽

Single Molecule ◽

Defense Mechanism ◽

Methylation Status ◽

Purifying Selection ◽

Dna Methyltransferases ◽

Epigenetic Mark ◽

Host Defense Mechanism ◽

Domains Of Life ◽

Giant Viruses

AbstractDNA methylation is an important epigenetic mark that contributes to various regulations in all domains of life. Prokaryotes use it through Restriction-Modification (R-M) systems as a host-defense mechanism against viruses. The recently discovered giant viruses are widespread dsDNA viruses infecting eukaryotes with gene contents overlapping the cellular world. While they are predicted to encode DNA methyltransferases (MTases), virtually nothing is known about the DNA methylation status of their genomes. Using single-molecule real-time sequencing we studied the complete methylome of a large spectrum of families: the Marseilleviridae, the Pandoraviruses, the Molliviruses, the Mimiviridae along with their associated virophages and transpoviron, the Pithoviruses and the Cedratviruses (of which we report a new strain). Here we show that DNA methylation is widespread in giant viruses although unevenly distributed. We then identified the corresponding viral MTases, all of which are of bacterial origins and subject to intricate gene transfers between bacteria, viruses and their eukaryotic host. If some viral MTases undergo pseudogenization, most are conserved, functional and under purifying selection, suggesting that they increase the viruses’ fitness. While the Marseilleviridae, Pithoviruses and Cedratviruses DNA MTases catalyze N6-methyl-adenine modifications, some MTases of Molliviruses and Pandoraviruses unexpectedly catalyze the formation of N4-methyl-cytosine modifications. In Marseilleviridae, encoded MTases are paired with cognate restriction endonucleases (REases) forming complete R-M systems. Our data suggest that giant viruses MTases could be involved in different kind of virus-virus interactions during coinfections.

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Natural selection and repeated patterns of molecular evolution following allopatric divergence

eLife ◽

10.7554/elife.45199 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 6

Author(s):

Yibo Dong ◽

Shichao Chen ◽

Shifeng Cheng ◽

Wenbin Zhou ◽

Qing Ma ◽

...

Keyword(s):

Positive Selection ◽

Divergence Time ◽

Purifying Selection ◽

Single Copy ◽

Orthologous Genes ◽

Allopatric Species ◽

Genome Wide ◽

Allopatric Divergence ◽

Selective Forces ◽

Repeated Pattern

Although geographic isolation is a leading driver of speciation, the tempo and pattern of divergence at the genomic level remain unclear. We examine genome-wide divergence of putatively single-copy orthologous genes (POGs) in 20 allopatric species/variety pairs from diverse angiosperm clades, with 16 pairs reflecting the classic eastern Asia-eastern North America floristic disjunction. In each pair, >90% of POGs are under purifying selection, and <10% are under positive selection. A set of POGs are under strong positive selection, 14 of which are shared by 10–15 pairs, and one shared by all pairs; 15 POGs are annotated to biological processes responding to various stimuli. The relative abundance of POGs under different selective forces exhibits a repeated pattern among pairs despite an ~10 million-year difference in divergence time. Species divergence times are positively correlated with abundance of POGs under moderate purifying selection, but negatively correlated with abundance of POGs under strong purifying selection.

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Molecular evolution of dengue 2 virus in Puerto Rico: positive selection in the viral envelope accompanies clade reintroduction

Journal of General Virology ◽

10.1099/vir.0.81309-0 ◽

2006 ◽

Vol 87 (4) ◽

pp. 885-893 ◽

Cited By ~ 83

Author(s):

Shannon N. Bennett ◽

Edward C. Holmes ◽

Maritza Chirivella ◽

Dania M. Rodriguez ◽

Manuela Beltran ◽

...

Keyword(s):

Puerto Rico ◽

Molecular Evolution ◽

Positive Selection ◽

Disease Incidence ◽

Phylogenetic Analyses ◽

Acid Sites ◽

Viral Envelope ◽

Envelope Gene ◽

Structural Genes ◽

Phylogenetic Structure

Dengue virus is a circumtropical, mosquito-borne flavivirus that infects 50–100 million people each year and is expanding in both range and prevalence. Of the four co-circulating viral serotypes (DENV-1 to DENV-4) that cause mild to severe febrile disease, DENV-2 has been implicated in the onset of dengue haemorrhagic fever (DHF) in the Americas in the early 1980s. To identify patterns of genetic change since DENV-2's reintroduction into the region, molecular evolution in DENV-2 from Puerto Rico (PR) and surrounding countries was examined over a 20 year period of fluctuating disease incidence. Structural genes (over 20 % of the viral genome), which affect viral packaging, host-cell entry and immune response, were sequenced for 91 DENV-2 isolates derived from both low- and high-prevalence years. Phylogenetic analyses indicated that DENV-2 outbreaks in PR have been caused by viruses assigned to subtype IIIb, originally from Asia. Variation amongst DENV-2 viruses in PR has since largely arisen in situ, except for a lineage-replacement event in 1994 that appears to have non-PR New World origins. Although most structural genes have remained relatively conserved since the 1980s, strong evidence was found for positive selection acting on a number of amino acid sites in the envelope gene, which have also been important in defining phylogenetic structure. Some of these changes are exhibited by the multiple lineages present in 1994, during the largest Puerto Rican outbreak of dengue, suggesting that they may have altered disease dynamics, although their functional significance will require further investigation.

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Evolutionary History of the Toll-Like Receptor Gene Family across Vertebrates

Genome Biology and Evolution ◽

10.1093/gbe/evz266 ◽

2019 ◽

Vol 12 (1) ◽

pp. 3615-3634 ◽

Cited By ~ 6

Author(s):

Guangshuai Liu ◽

Huanxin Zhang ◽

Chao Zhao ◽

Honghai Zhang

Keyword(s):

Positive Selection ◽

Gene Family ◽

Evolutionary History ◽

Phylogenetic Analyses ◽

Receptor Gene ◽

Purifying Selection ◽

Protein Architecture ◽

Wide Range ◽

History Of ◽

Membrane Bound

Abstract Adaptation to a wide range of pathogenic environments is a major aspect of the ecological adaptations of vertebrates during evolution. Toll-like receptors (TLRs) are ancient membrane-bound sensors in animals and are best known for their roles in detecting and defense against invading pathogenic microorganisms. To understand the evolutionary history of the vertebrate TLR gene family, we first traced the origin of single-cysteine cluster TLRs that share the same protein architecture with vertebrate TLRs in early-branching animals and then analyzed all members of the TLR family in over 200 species covering all major vertebrate clades. Our results indicate that although the emergence of single-cysteine cluster TLRs predates the separation of bilaterians and cnidarians, most vertebrate TLR members originated shortly after vertebrate emergence. Phylogenetic analyses divided 1,726 vertebrate TLRs into 8 subfamilies, and TLR3 may represent the most ancient subfamily that emerged before the branching of deuterostomes. Our analysis reveals that purifying selection predominated in the evolution of all vertebrate TLRs, with mean dN/dS (ω) values ranging from 0.082 for TLR21 in birds to 0.434 for TLR11 in mammals. However, we did observe patterns of positive selection acting on specific codons (527 of 60,294 codons across all vertebrate TLRs, 8.7‰), which are significantly concentrated in ligand-binding extracellular domains and suggest host–pathogen coevolutionary interactions. Additionally, we found stronger positive selection acting on nonviral compared with viral TLRs, indicating the more essential nonredundant function of viral TLRs in host immunity. Taken together, our findings provide comprehensive insight into the complex evolutionary processes of the vertebrate TLR gene family, involving gene duplication, pseudogenization, purification, and positive selection.

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Functional Bias and Demographic History Obscure Patterns of Selection among Single-Copy Genes in a Fungal Species Complex

10.1101/107326 ◽

2017 ◽

Author(s):

Santiago Sánchez-Ramírez ◽

Jean-Marc Moncalvo

Keyword(s):

Natural Selection ◽

Positive Selection ◽

Dna Sequences ◽

Demographic History ◽

Purifying Selection ◽

Single Copy ◽

Fungal Species ◽

Ratio Test ◽

Ontology Term ◽

Slightly Deleterious Mutations

AbstractMany different evolutionary processes may be responsible for explaining natural variation within genomes, some of which include natural selection at the molecular level and changes in population size. Fungi are highly adaptable organisms, and their relatively small genomes and short generation times make them pliable for evolutionary genomic studies. However, adaptation in wild populations has been relatively less documented compared to experimental or clinical studies. Here, we analyzed DNA sequences from 502 putative single-copy orthologous genes in 63 samples that represent seven recently diverged North American Amanita (jacksonii-complex) lineages. For each gene and each species, we measured the genealogical sorting index (gsi) and infinite-site-based summary statistics, such as , and DTaj in coding and intron regions. MKT-based approaches and likelihood-ratio-test Kn/Ks models were used to measure natural selection in all coding sequences. Multi-locus (Extended) Bayesian Skyline Plots (eBSP) were used to model intraspecific demographic changes through time based on unlinked, putative neutral regions (introns). Most genes show evidence of long-term purifying selection, likely reflecting a functional bias implicit in single-copy genes. We find that two species have strongly negatively skewed Tajima’s D, while three other have a positive skew, corresponding well with patterns of demographic expansion and contraction. Standard MKT analyses resulted in a high incidence of near-zero α with a tendency towards negative values. In contrast, α estimates based on the distribution of fitness effects (DFE), which accounts for demographic effects and slightly deleterious mutations, suggest a higher proportion of sites fixed by positive selection. The difference was more notorious in species with expansion signatures or with historically low population sizes, evidencing the concealing effects of specific demographic histories. Finally, we attempt to mitigate Gene Ontology term overrepresentation, highlighting the potential adaptive or ecological roles of some genes under positive selection.

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Targeted Enrichment of Large Gene Families for Phylogenetic Inference: Phylogeny and Molecular Evolution of Photosynthesis Genes in the Portullugo (Caryophyllales)

10.1101/145995 ◽

2017 ◽

Author(s):

Abigail J. Moore ◽

Jurriaan M. de Vos ◽

Lillian P. Hancock ◽

Eric Goolsby ◽

Erika J. Edwards

Keyword(s):

Molecular Evolution ◽

Phylogenetic Analyses ◽

Strong Support ◽

Gene Families ◽

Sister Group ◽

Single Copy ◽

Gene Trees ◽

Evolutionary Transitions ◽

Large Gene ◽

Cam Photosynthesis

ABSTRACTHybrid enrichment is an increasingly popular approach for obtaining hundreds of loci for phylogenetic analysis across many taxa quickly and cheaply. The genes targeted for sequencing are typically single-copy loci, which facilitate a more straightforward sequence assembly and homology assignment process. However, single copy loci are relatively uncommon elements of most genomes, and as such may provide a biased evolutionary history. Furthermore, this approach limits the inclusion of most genes of functional interest, which often belong to multi-gene families. Here we demonstrate the feasibility of including large gene families in hybrid enrichment protocols for phylogeny reconstruction and subsequent analyses of molecular evolution, using a new set of bait sequences designed for the “portullugo” (Caryophyllales), a moderately sized lineage of flowering plants (~2200 species) that includes the cacti and harbors many evolutionary transitions to C4 and CAM photosynthesis. Including multi-gene families allowed us to simultaneously infer a robust phylogeny and construct a dense sampling of sequences for a major enzyme of C4 and CAM photosynthesis, which revealed the accumulation of adaptive amino acid substitutions associated with C4 and CAM origins in particular paralogs. Our final set of matrices for phylogenetic analyses included 75–218 loci across 74 taxa, with ~50% matrix completeness across datasets. Phylogenetic resolution was greatly improved across the tree, at both shallow and deep levels. Concatenation and coalescent-based approaches both resolve with strong support the sister lineage of the cacti: Anacampserotaceae + Portulacaceae, two lineages of mostly diminutive succulent herbs of warm, arid regions. In spite of this congruence, BUCKy concordance analyses demonstrated strong and conflicting signals across gene trees for the resolution of the sister group of the cacti. Our results add to the growing number of examples illustrating the complexity of phylogenetic signals in genomic-scale data.

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Molecular Evolution of SARS-CoV-2 Structural Genes: Evidence of Positive Selection in the Spike Glycoprotein

10.21203/rs.3.rs-42498/v2 ◽

2020 ◽

Author(s):

Xiao-Yong Zhan ◽

Ying Zhang ◽

Xuefu Zhou ◽

Ke Huang ◽

Yichao Qian ◽

...

Keyword(s):

Molecular Evolution ◽

Positive Selection ◽

Signal Sequence ◽

Phylogenetic Analyses ◽

Host Cells ◽

Public Health Issue ◽

Intragenic Recombination ◽

Structural Genes ◽

S Protein ◽

Spike Gene

Abstract Background: SARS-CoV-2 has caused a global pandemic since early 2020 and remains a serious public health issue worldwide. Four structural genes, envelope (E), membrane (M), nucleocapsid (N) and spike (S), play a key role in controlling entry into human cells and virion assembly of SARS-CoV-2. The evolution of these genes may determine infectivity of SARS-CoV-2, but thus far, little is known about them. Methods: We analyzed 3090 SARS-CoV-2 isolates from the GenBank database to determine the evolutionary patterns of the four structural genes by employing various molecular evolution algorithms. Results: Phylogenetic analyses showed that global SARS-CoV-2 isolates can be clustered into three to four major clades based upon protein sequence. Although intragenic recombination was not detected among different alleles, purifying selection has affected the evolution of these genes. By analyzing full genomic sequences of these alleles, our result revealed that codon 614 of the S glycoprotein has been subjected to a strong positive selection pressure, and a consistent D614G mutation was identified. Additionally, another potentially positive selection site at codon 5 in the signal sequence of the S protein was also identified with a consistent L5F mutation. The allele containing the D614G mutation has undergone significant expansion during SARS-CoV-2 transmission, implying a better adaptability of isolates with the mutation. Nevertheless, L5F allele expansion was found to be relatively restricted. The D614G mutation is located at subdomain 2 (SD2) of the C-terminal portion (CTP) of the S1 subunit. Protein structural modeling showed that the D614G mutation may cause the disruption of a salt bridge between S protein monomers and increase their flexibility, consequently promoting receptor binding domain (RBD) opening, virus attachment, and ultimately entry into host cells. Located at the signal sequence of S protein, the L5F mutation may facilitate protein folding, assembly, and secretion of the virus. Conclusions: This is the first reported evidence of positive Darwinian selection in the spike gene of SARS-CoV-2. This finding contributes to a broader understanding of the adaptive mechanisms of this virus, and provide insight for the development of novel therapeutic approaches, as well as the creation of effective vaccines, through targeting mutation sites.

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Evolutionary dynamics of chloroplast genomes in low light: a case study of the endolithic green algaOstreobium quekettii

10.1101/049833 ◽

2016 ◽

Author(s):

Vanessa R. Marcelino ◽

Ma Chiela M. Cremen ◽

Christopher J. Jackson ◽

Anthony W.D. Larkum ◽

Heroen Verbruggen

Keyword(s):

Molecular Evolution ◽

Positive Selection ◽

Chloroplast Genome ◽

Evolutionary Dynamics ◽

Purifying Selection ◽

Light Sensitivity ◽

Light Limitation ◽

Comparative Genomic ◽

Low Light ◽

Chloroplast Genomes

Some photosynthetic organisms live in extremely low light environments. Light limitation is associated with selective forces as well as reduced exposure to mutagens, and over evolutionary timescales it can leave a footprint on species genome. Here we present the chloroplast genomes of four green algae (Bryopsidales, Ulvophyceae), including the endolithic (limestone-boring) alga Ostreobium quekettii, which is a low light specialist. We use phylogenetic models and comparative genomic tools to investigate whether the chloroplast genome of Ostreobium corresponds to our expectations of how low light would affect genome evolution. Ostreobium has the smallest and most gene-dense chloroplast genome among Ulvophyceae reported to date, matching our expectation that light limitation would impose resource constraints. Rates of molecular evolution are significantly slower along the phylogenetic branch leading to Ostreobium, in agreement with the expected effects of low light and energy levels on molecular evolution. Given the exceptional ability of our model organism to photosynthesize under extreme low light conditions, we expected to observe positive selection in genes related to the photosynthetic machinery. However, we observed stronger purifying selection in these genes, which might either reflect a lack of power to detect episodic positive selection followed by purifying selection and/or a strengthening of purifying selection due to the loss of a gene related to light sensitivity. Besides shedding light on the genome dynamics associated with a low light lifestyle, this study helps to resolve the role of environmental factors in shaping the diversity of genome architectures observed in nature.

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