scholarly journals Non-synonymous to synonymous substitutions suggest that orthologs tend to keep their functions, while paralogs are a source of functional novelty

2018 ◽  
Author(s):  
Juan Miguel Escorcia-Rodríguez ◽  
Mario Esposito ◽  
Julio Augusto Freyre-González ◽  
Gabriel Moreno-Hagelsieb

AbstractBackgroundOrthologs diverge after speciation events and paralogs after gene duplication. It is thus expected that orthologs would tend to keep their functions, while paralogs could be a source of new functions. Because protein functional divergence follows from non-synonymous substitutions, we performed an analysis based on the ratio of non-synonymous to synonymous substitutions (dN/dS) as proxy for functional divergence. We used four working definitions of orthology, including reciprocal best hits (RBH), among other definitions based on network analyses and clustering.ResultsThe results showed that orthologs, by all definitions tested, had values of dN/dS noticeably lower than those of paralogs, not only suggesting that orthologs keep their functions better, but also that paralogs are a readily source of functional novelty. The differences in dN/dS ratios remained favouring the functional stability of orthologs after eliminating gene comparisons with potential problems, such as genes having a high codon usage bias, low coverage of either of the aligned sequences, or sequences with very high similarities. The dN/dS ratios kept suggesting better functional stability of orthologs regardless of overall sequence divergence. Separating orthologs and paralogs into groups with similar overall substitution rates kept showing dN/dS differences favouring the functional stability of orthologs over that of paralogs.AvailabilityA couple of programs for obtaining orthologs and dN/dS values as tested in this manuscript are available at github: https://github.com/Computational-conSequences/SequenceTools.

2020 ◽  
Author(s):  
Juan Miguel Escorcia-Rodriguez ◽  
Mario Esposito ◽  
Julio Augusto Freyre-Gonzalez ◽  
Gabriel Moreno-Hagelsieb

Abstract Background: Orthologs diverge after speciation events and paralogs after gene duplication. It is thus expected that orthologs would tend to keep their functions, while paralogs could be a source of new functions. Because protein functional divergence follows from non-synonymous substitutions, we performed an analysis based on the ratio of non-synonymous to synonymous substitutions (dN/dS) as proxy for functional divergence. We used four working definitions of orthology, including reciprocal best hits (RBH), among other definitions based on network analyses and clustering.Results: The results showed that orthologs, by all definitions tested, had values of dN/dS noticeably lower than those of paralogs, not only suggesting that orthologs keep their functions better, but also that paralogs are a readily source of functional novelty. The differences in dN/dS ratios remained favouring the functional stability of orthologs after eliminating gene comparisons with potential problems, such as genes having a high codon usage bias, low coverage of either of the aligned sequences, or sequences with very high similarities. The dN/dS ratios kept suggesting better functional stability of orthologs regardless of overall sequence divergence.Availability: A couple of programs for obtaining orthologs and dN/dS values as tested in this manuscript are available at github: https://github.com/Computational-conSequences/SequenceTools.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10426
Author(s):  
Jingjing Wang ◽  
Yuriy L. Orlov ◽  
Xue Li ◽  
Yincong Zhou ◽  
Yongjing Liu ◽  
...  

Background Genetic regulation is known to contribute to the divergent expression of duplicate genes; however, little is known about how epigenetic modifications regulate the expression of duplicate genes in plants. Methods The histone modification (HM) profile patterns of different modes of gene duplication, including the whole genome duplication, proximal duplication, tandem duplication and transposed duplication were characterized based on ChIP-chip or ChIP-seq datasets. In this study, 10 distinct HM marks including H2Bub, H3K4me1, H3K4me2, H3K4me3, H3K9ac, H3K9me2, H3K27me1, H3K27me3, H3K36me3 and H3K14ac were analyzed. Moreover, the features of gene duplication with different HM patterns were characterized based on 88 RNA-seq datasets of Arabidopsis thaliana. Results This study showed that duplicate genes in Arabidopsis have a more similar HM pattern than single-copy genes in both their promoters and protein-coding regions. The evolution of HM marks is found to be coupled with coding sequence divergence and expression divergence after gene duplication. We found that functionally selective constraints may impose on epigenetic evolution after gene duplication. Furthermore, duplicate genes with distinct functions have more divergence in histone modification compared with the ones with the same function, while higher expression divergence is found with mutations of chromatin modifiers. This study shows the role of epigenetic marks in regulating gene expression and functional divergence after gene duplication in plants based on sequencing data.


2021 ◽  
Vol 22 (6) ◽  
pp. 3012
Author(s):  
James I. Mitchell-White ◽  
Thomas Stockner ◽  
Nicholas Holliday ◽  
Stephen J. Briddon ◽  
Ian D. Kerr

The five members of the mammalian G subfamily of ATP-binding cassette transporters differ greatly in their substrate specificity. Four members of the subfamily are important in lipid transport and the wide substrate specificity of one of the members, ABCG2, is of significance due to its role in multidrug resistance. To explore the origin of substrate selectivity in members 1, 2, 4, 5 and 8 of this subfamily, we have analysed the differences in conservation between members in a multiple sequence alignment of ABCG sequences from mammals. Mapping sets of residues with similar patterns of conservation onto the resolved 3D structure of ABCG2 reveals possible explanations for differences in function, via a connected network of residues from the cytoplasmic to transmembrane domains. In ABCG2, this network of residues may confer extra conformational flexibility, enabling it to transport a wider array of substrates.


2020 ◽  
Vol 21 (5) ◽  
pp. 1752 ◽  
Author(s):  
Jin Yang ◽  
Jie Zhou ◽  
Hong-Jun Zhou ◽  
Mang-Mang Wang ◽  
Ming-Ming Liu ◽  
...  

Phosphate (Pi) transporters play critical roles in Pi acquisition and homeostasis. However, currently little is known about these genes in oil crops. In this study, we aimed to characterize the five Pi transporter gene families (PHT1-5) in allotetraploid Brassica napus. We identified and characterized 81 putative PHT genes in B. napus (BnaPHTs), including 45 genes in PHT1 family (BnaPHT1s), four BnaPHT2s, 10 BnaPHT3s, 13 BnaPHT4s and nine BnaPHT5s. Phylogenetic analyses showed that the largest PHT1 family could be divided into two groups (Group I and II), while PHT4 may be classified into five, Groups I-V. Gene structure analysis revealed that the exon-intron pattern was conservative within the same family or group. The sequence characteristics of these five families were quite different, which may contribute to their functional divergence. Transcription factor (TF) binding network analyses identified many potential TF binding sites in the promoter regions of candidates, implying their possible regulating patterns. Collinearity analysis demonstrated that most BnaPHTs were derived from an allopolyploidization event (~40.7%) between Brassica rapa and Brassica oleracea ancestors, and small-scale segmental duplication events (~39.5%) in the descendant. RNA-Seq analyses proved that many BnaPHTs were preferentially expressed in leaf and flower tissues. The expression profiles of most colinearity-pairs in B. napus are highly correlated, implying functional redundancy, while a few pairs may have undergone neo-functionalization or sub-functionalization during evolution. The expression levels of many BnaPHTs tend to be up-regulated by different hormones inductions, especially for IAA, ABA and 6-BA treatments. qRT-PCR assay demonstrated that six BnaPHT1s (BnaPHT1.11, BnaPHT1.14, BnaPHT1.20, BnaPHT1.35, BnaPHT1.41, BnaPHT1.44) were significantly up-regulated under low- and/or rich- Pi conditions in B. napus roots. This work analyzes the evolution and expression of the PHT family in Brassica napus, which will help further research on their role in Pi transport.


2021 ◽  
Author(s):  
Stefano Pascarelli ◽  
Paola Laurino

Connecting protein sequence to function is becoming increasingly relevant since high-throughput sequencing studies accumulate large amounts of genomic data. Protein database annotation helps to bridge this gap; however, it is fundamental to understand the mechanisms underlying functional inheritance and divergence. If the homology relationship between proteins is known, can we determine whether the function diverged? In this work, we analyze different possibilities of protein sequence evolution after gene duplication and identify "residue inversions", i.e., sites where the relationship between the ancestry and the functional signal is decoupled. Residues in these sites play a role in functional divergence and could indicate a shift in protein function. We develop a method to recognize residue inversions in a phylogeny and test it on real and simulated datasets. In a dataset built from the Epidermal Growth Factor Receptor (EGFR) sequences found in 88 fish species, we identify 19 positions that went through inversion after gene duplication, mostly located at the ligand-binding extracellular domain.


2020 ◽  
Vol 230 (1) ◽  
pp. 37-37
Author(s):  
Aissette Baanannou ◽  
Sepand Rastegar ◽  
Amal Bouzid ◽  
Masanari Takamiya ◽  
Vanessa Gerber ◽  
...  

2008 ◽  
Vol 8 (1) ◽  
pp. 259 ◽  
Author(s):  
Angèle Tingaud-Sequeira ◽  
François Chauvigné ◽  
Mercedes Fabra ◽  
Juanjo Lozano ◽  
Demetrio Raldúa ◽  
...  

2011 ◽  
Vol 50 (3-4) ◽  
pp. 235-248 ◽  
Author(s):  
Changgui Dong ◽  
Junpeng Zhang ◽  
Jian Qiao ◽  
Guimei He

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