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At least 19 recordsLinked to original sources
PubMed2026

Asymmetric Functional Divergence of alx4a and alx4b in Iridophore Differentiation and Cranial Development in Nile Tilapia.

Neural crest cells give rise to the craniofacial skeleton and multiple pigment cell lineages, yet how duplicated developmental regulators partition their ancestral functions after teleost-specific whole-genome duplication remains unclear. Here, we employed CRISPR/Cas9 to generate alx4a and alx4b single and double mutants in Nile tilapia (Oreochromis niloticus). By integrating phenotype, skeleton, transcriptome, quantitative PCR, and AlphaFold-based structural modeling analyses, we revealed their functional divergence. Loss of alx4a caused a regionally restricted reduction in iridophore-derived reflectance and abnormal cranial morphology, whereas alx4b single mutants showed no obvious phenotype under the conditions examined. By contrast, double mutants exhibited an almost complete loss of iridophore-derived structural coloration and substantially more severe cranial defects, accompanied by reduced calcein labeling in the opercular region, consistent with altered cranial mineralization. Skin transcriptomic and quantitative PCR analyses revealed marked downregulation of pnp4a and tfec, which are associated with iridophore differentiation and coloration, whereas no significant expression differences were detected for the iridophore survival-related genes ltk and mpv17. AlphaFold2-assisted HDOCK protein-DNA modeling yielded more favorable docking metrics for Alx4a than for Alx4b with the pnp4a promoter, supporting a potential Alx4a-pnp4a promoter interaction that requires experimental validation. In contrast, no significant genotype-dependent differences were detected in the measured abundance of melanophores, xanthophores, or erythrophores, and no obvious difference in gross dorsal-fin spine formation was observed under the conditions examined. Together, these findings reveal unequal functional contributions of alx4a and alx4b, with alx4a acting as the dominant paralog in iridophore-associated structural coloration and both paralogs contributing unequally to cranial development, and support pnp4a as a candidate downstream gene associated with Alx4a activity.

Animals↗
PubMed2025

Analysis of Duplication and Potential Functional Divergence of Wing Gene Network Components in Pea Aphids.

A fundamental focus of evolutionary developmental biology is uncovering the genetic mechanisms responsible for the gain and loss of characters. One approach to this question is to investigate changes in the coordinated expression of a group of genes important for the development of a character of interest (a gene regulatory network). Here we consider the possibility that modifications to the wing gene regulatory network (wGRN), as defined by work primarily done in Drosophila melanogaster, were involved in the evolution of wing dimorphisms of the pea aphid (Acyrthosiphon pisum). We hypothesize that this may have occurred via changes in expression levels or by duplication followed by divergence of wGRN components. To test this, we annotated members of the wGRN in the pea aphid genome and assessed their expression levels in first and third nymphal instars of winged and wingless morphs of males and asexual females. We find that only 2 of the 32 assessed genes exhibit morph-biased expression. We also find that three wing genes (apterous (ap), warts (wts), and decapentaplegic (dpp)) have undergone gene duplication. In each case, the resulting paralogs show signs consistent with functional divergence, exhibiting either sex-, morph-, or stage-specific expression. Two gene duplicates, wts2 and dpp3, are of particular interest with respect to wing dimorphism, as they exhibit male morph-specific isoforms and wingless male-biased expression, respectively. These gene expression results provide an important first step toward identifying members of the pea aphid wGRN that may play a causative role in differentiating winged from wingless morphs. These findings supplement our understanding of trends in developmental gene network evolution, such as side-stepping pleiotropic constraint via duplication and sub-functionalization, underlying the emergence of novel phenotypes.

Animals↗
PubMed2026

Divergent PXR function in seals: Endocrine adaptation or functional loss?

Seals accumulate xenobiotics through dietary biomagnification and exposure to polluted marine environments, with contaminants concentrating in their blubber. Biotransformation mitigates xenobiotic toxicity by converting lipophilic compounds into excretable hydrophilic metabolites, a process coordinated by nuclear receptors including the Pregnane X Receptor (PXR), whose plastic ligand-binding domain enables broad xenobiotic sensing. By examining PXR in pinnipeds, we investigated the evolutionary conservation and functional characterization of PXR using genomic sequence analysis, protein structural prediction, and transactivation assays, revealing broadly conserved structural features alongside species-specific functional divergence in receptor responsiveness to environmental stressors. Specifically, the obtained results highlight divergent gene and functional landscapes with ORF-disrupting mutations identified in Monachus monachus and Neomonachus schauinslandi that abolish receptor activation toward known PXR ligands. In contrast, Leptonychotes weddelli retained an intact PXR ORF but showed reduced receptor activity, revealing functional divergence in PXR among pinnipeds.

Biotransformation↗
PubMed2026

Functional divergence of two soybean cytosolic serine hydroxymethyltransferases in development and defense against soybean cyst nematode.

Serine hydroxymethyltransferase (SHMT) is an enzyme essential for one-carbon metabolism. In higher plants, multiple SHMT genes code for isoforms that function in the cytosol, nucleus, mitochondria, and chloroplasts. The soybean genome contains two cytosolic SHMTs, GmSHMT05 and GmSHMT08, sharing high sequence identity and similar expression throughout soybean development. In certain soybean genotypes, two amino acid substitutions negatively impact GmSHMT08's ability to bind to tetrahydrofolate (THF), leading to a gain-of-function in resistance to the soybean cyst nematode (SCN). Whether this perturbation to the enzyme has other functional consequences for soybean growth and development remains unknown. Here, we investigated the roles of cytosolic GmSHMTs in soybean growth and development. We determined that the 3D structure and folate-binding affinity of GmSHMT05 are highly similar to the version of GmSHMT08 found in susceptible soybeans. We further measured phenotypic traits of two ethyl methanesulfonate-derived Gmshmt08 mutant plants in an SCN-resistant soybean background. Aboveground soybean growth and development were similar, except the Gmshmt08 mutant plants showed a significant increase in pods/plant in field phenotyping trials. Belowground analyses revealed a significant increase in lateral root and total root length in mutant plants, and CRISPR-Cas9 editing demonstrated an essential role of cytosolic SHMTs in root growth. Taken together, our results indicate that GmSHMT05 sustains overall soybean growth and development in the absence of GmSHMT08; however, GmSHMT08's gain-of-function in SCN resistance negatively influences pod and root growth, highlighting a potential trade-off between soybean defense and development that may impact yield when breeding with GmSHMT08 to develop SCN-resistant varieties.

1-C folate metabolism↗
PubMed1982

Mouse kallikrein arginyl-esteropeptidase genes: analysis of cloned cDNAs suggests rapid functional divergence from a common ancestral sequence.

A previously-cloned cDNA coding for a member of the kallikrein arginyl-esteropeptidase group of serine proteases, (pMK-1), was used as a hybridization probe to identify a second partial cDNA clone (pMK-2) from mouse submaxillary gland. pMK-2 shares more than a 98% nucleotide sequence homology with pMK-1; the 3' untranslated regions are identical and there are only two predicted amino acid changes over the C-terminal 66 amino acids. The site of one change is implicated in determining substrate specificity, while the other may affect the catalytic mechanism. Thus despite the marked similarity of pMK-1 and pMK-2, the differences probably give rise to functionally distinct enzymes and are not simply polymorphic alleles.

Amino Acid Sequence↗
PubMed1975

Lactate dehydrogenase isozymes of salmonid fish. Evidence for unique and rapid functional divergence of duplicated H-4 lactate dehydrogenases.

Salmonid fish, as a result of total genome duplication, have two genes, Ldh H and Ldh H', coding for polypeptides H and H', respectively, both of which have been shown in their tetrameric forms to be immunologically related to the classical H-4 lactate dehydrogenase isozyme of higher vertebrates (Bailey, G. S., and Wilson, A. C. (1968) J. Biol. Chem. 243,5843). The H-4 and H'-4 isozymes have now been highly purified from quinnat salmon, and their chemical, physical, immunological, and catalytic properties examined, and compared to the M-4 isozyme of salmon. The two proteins H-4 and H'-4 are shown to be very similar in amino acid composition, but significant differences in a few residues suggest differences in amino acid sequences. This suggestion was born out by quantitative immunological experiments in which the H-4 and H'-4 isozymes were shown to be about as different from each other as are the H-4 lactate dehydrogenases of chicken and duck. This suggests that the gene duplication event in salmon which give rise to two Ldh H genes occurred approximately 80 to 100 million years ago. The H'-4 lactate dehydrogenase which has risen from this duplication in salmon is shown to be somewhat intermediate between H-4 and M-4 in thermal stability, and in all catalytic properties examined, including substrate optima, Michaelis constants, and susceptibility to inhibition by high levels of substrate. In particular the H'-4 isozyme is almost exactly intermediate between H-4 and M-4 in its resistance to product inhibition by lactate, the catalytic parameter suggested to be of major functional importance to M-4 lactate dehydrogenase isozymes (Stambaugh, R., and Post D. (1966) J. Biol. Chem. 241,1462). Further, tissue distribution of these isozymes in salmon and trout are shown to be unusual. The M-4 isozyme salmon and trout are shown to be unusual. The M-4 isozyme occurs in very few tissues in detectable levels. It is the H-4 and H'-4 rather than H-4 and M-4, which occur in independently variable but significant levels in most tissues examined. Thus the H'-4 isozyme, despite its very close structural similarity to H-4 appears to possess functional properties which are different from either H-4 or M-4 in salmon, and some properties are midway between the two. This finding, together with the unusual tissue distribution of these isozymes, suggests that salmon with H'-4 lactate dehydrogenase is evolving to function catalytically in the absence of a balanced H-4-M-4 isozyme complement in most tissues. This balance seems to be met in most tissues by combinations of H-4 and H'-4,

Amino Acids↗
PubMed1989

Mechanistic and functional divergence between thyrotropin-releasing hormone and RO 15-4513 interactions with ethanol.

Both thyrotropin-releasing hormone (TRH) and RO 15-4513 antagonize ethanol-induced depression, but this common property does not infer that both compounds share similar mechanisms of action. In the present studies, both TRH (30 mg/kg, i.p.) and RO 15-4513 (10 mg/kg, i.p.) reversed ethanol-induced depression of locomotor activity, in accord with previous reports. However, the benzodiazepine antagonist, RO 15-1788, blocked this action of RO 15-4513, while exerting no effect on the analeptic action of TRH. Using a model of seizure activity electrically elicited from the inferior colliculus, ethanol exerted a dose-related attenuation of seizure activity. This anticonvulsant action of ethanol was not altered by TRH (30 mg/kg, i.p.), but RO 15-4513 (3 mg/kg) reversed the effect of the 0.5, but not the 1.0 g/kg, dose of ethanol. In addition, pretreatment with RO 15-4513 (1 or 3 mg/kg, i.p.), but not TRH (30 mg/kg, i.p.), caused seizure generalization into the forebrain following inferior collicular stimulation, further verifying the proconvulsant properties of RO 15-4513. In conclusion, the analeptic action of TRH appears independent of benzodiazepine activity, and in contrast to RO 15-4513, TRH does not exhibit proconvulsant properties. Furthermore, because TRH did not antagonize both depressant actions of ethanol studied, it appears unlikely that TRH directly interacts with the molecular basis of ethanol action.

Animals↗
PubMed1989

Homologous rat hepatic protease inhibitor genes show divergent functional responses to inflammation.

The genes encoding three distinct serine protease inhibitors (Spi) have been cloned from rat liver. These inhibitors are highly homologous with each other and are similar to alpha 1-antitrypsin at the nucleic and amino acid sequence level. Although previous investigators have examined the regulation of the Spi 2 locus by inflammation, the use of various techniques and the complexity of this genetic locus have led to incomplete and somewhat confusing results. Oligonucleotide probes specific for Spi 2.1, Spi 2.2, Spi 2.3, and a 3' mouse cDNA probe for alpha 1-antitrypsin mRNA were used to measure these mRNA after induction of inflammation with subcutaneous turpentine in Fischer rats. alpha 1-Antitrypsin mRNA increased 1.8-fold, and Spi 2.2 increased 7-fold. In contrast, Spi 2.1 and 2.3 mRNA sequences decreased fourfold. The maximal changes occurred between 24 and 48 h after inflammation, with a gradual return toward normal over the next 4 days. Since Spi 2.1, Spi 2.3, and alpha 1-antitrypsin mRNA sequences are responsive to growth hormone, two other growth hormone-responsive mRNA sequences, alpha 2u-globulin and insulin-like growth factor I, were measured, and they also decreased after induction of inflammation. The results of this study show that, despite a marked similarity of nucleotide sequence, Spi 2.1 and 2.3 genes respond very differently from Spi 2.2 and alpha 1-antitrypsin to both growth hormone and inflammation. We speculate that the functions of Spi 2.1 and 2.3 products are different from those of Spi 2.2 and alpha 1-antitrypsin and may involve the regulation of growth.

Animals↗
PubMed2025

Evolution of primate T-cell leukemia virus type 1 accessory genes and functional divergence of its antisense proteins.

Human T-cell leukemia virus type 1 (HTLV-1) is derived from simian T-cell leukemia virus type 1 (STLV-1), and together they form a broader category known as primate T-cell leukemia virus type 1 (PTLV-1). PTLV-1 encodes multiple proteins from overlapping open reading frames (ORFs) in the pX region. This study aims to characterize the conservation of these proteins in different PTLV-1 subtypes and their role in pathogenesis. For the first time, we report the full-length proviral sequence of an STLV-1 strain isolated from chimpanzee and African green monkey. Phylogenetic analysis reveals high conservation of the accessory proteins p12, p30, and p13 in the HTLV-1a subtype. Conversely, some African PTLV-1 subtypes exhibit loss of ORFs for p12 or p13. For Asian subtypes, simian strains often lack p12, p13, or p30 proteins, whereas human strains retain the ORFs of p30 and p13 but not p12. To assess the infectivity of a simian strain of PTLV-1 lacking ORFs for p12, p13, and p30, we constructed a molecular clone from a naturally infected Japanese macaque (Mfu: Macaca fuscata) and compared it with HTLV-1a. Using a reporter assay and ELISA, we found similar infectivity to Jurkat T cells; however, STLV-1 Mfu exhibited impaired infectivity in the monocytic cell line THP-1. Additionally, despite the conservation of the HTLV-1/STLV-1 bZIP factor (HBZ/SBZ) ORFs, HBZ/SBZ proteins derived from HTLV-1a and African PTLV-1 subtypes induce significantly higher activation of the TGF-β/Smad signaling pathway than those from Asian subtypes. Collectively, our findings suggest that the acquisition of the accessory proteins by PTLV-1 subtypes potentially confers an advantageous adaptation of PTLV-1 during infection in apes, including humans. Moreover, among PTLV-1 strains, HBZ/SBZ had varying degrees of activity on the TGF-β/Smad pathway; this fact underscores the complex interplay between viral proteins and host signaling pathways, possibly influencing the viral pathogenicity in different species.

Animals↗
PubMed2025

Subgenomic divergence and functional innovation following whole-genome duplication in Maleae species of Rosaceae.

Whole-genome duplication (WGD) drives plant evolution by inducing karyotype rearrangements and gene loss through subgenome fractionation. In this study, we investigate post-WGD evolutionary dynamics in Rosaceae, focusing on Maleae species, which uniquely experienced an additional WGD. Using phylogenetic and synteny analyses, we reveal that chromosomal breakpoints act as hotspots for localized fractionation, contributing to blurred homoeologous origins and influencing gene retention patterns. Here, we reconstruct karyotype evolution across Rosaceae subfamilies, highlighting chromosome reductions and lineage-specific rearrangements in Dryadoideae, Rosoideae, and Amygdaloideae. We also identify a bias for retaining transcription factors and hormone-related genes from older WGDs in subsequent polyploidy events. Transcriptome analysis classifies WGD-derived genes in Maleae species, such as apple and loquat, into three expression groups, with hormone-enriched genes playing roles in lignification and fruit-related innovations. These findings demonstrate the interplay between chromosomal breakpoints, biased retention, and functional divergence, revealing their contributions to genomic and phenotypic evolution in Maleae and their adaptive success within Rosaceae.

Genome, Plant↗
PubMed2025

Complex and Dynamic Gene-by-Age and Gene-by-Environment Interactions Underlie Functional Morphological Variation in Adaptive Divergence in Arctic Charr (Salvelinus alpinus).

The evolution of adaptive phenotypic divergence requires heritable genetic variation. However, it is underappreciated that trait heritability is molded by developmental processes interacting with the environment. We hypothesized that the genetic architecture of divergent functional traits was dependent on age and foraging environment. Thus, we induced plasticity in full-sib families of Arctic charr (Salvelinus alpinus) morphs from two Icelandic lakes by mimicking prey variation in the wild. We characterized variation in body shape and size at two ages and investigated their genetic architecture with quantitative trait locus (QTL) analysis. Age had a greater effect on body shape than diet in most families, suggesting that development strongly influences phenotypic variation available for selection. Consistent with our hypothesis, multiple QTL were detected for all traits and their location depended on age and diet. Many of the genome-wide QTL were located within a subset of duplicated chromosomal regions suggesting that ancestral whole genome duplication events have played a role in the genetic control of functional morphological variation in the species. Moreover, the detection of two body shape QTL after controlling for the effects of age provides additional evidence for genetic variation in the plastic response of morphological traits to environmental variation. Thus, functional morphological traits involved in phenotypic divergence are molded by complex genetic interactions with development and environment.

Animals↗
PubMed1991

DNA sequence divergence and functional conservation at the STB locus of yeast 2 microns circle variants.

2 microns DNA isolated from industrial Saccharomyces cerevisiae yeasts exhibited extensive restriction fragment length polymorphisms. At least five 2 microns species were identified from eleven [cir+] strains. Southern hybridization mapped restriction fragment length polymorphisms at STB, a cis-acting locus essential for plasmid partitioning. Some 2 microns variants (e.g., 4110-2 microns and 4108-2 microns) had an altered number of 125-bp consensus repeats at STB. However, the corresponding region of 7754-2 microns has only approximately 70% nucleotide sequence homology with the 125-bp STB consensus repeat. YRp plasmids containing 7754-2 microns STB behave as YEp plasmids in laboratory yeasts, thereby indicating STB sequence divergence coupled to conservation of function.

Alleles↗
PubMed1980

Nucleotide sequence divergence and functional constraint in mRNA evolution.

Comparison of about 50 pairs of homologous nucleotide sequences for different genes revealed that the substitutions between synonymous codons occurred at much higher rates than did amino acid substitutions. Furthermore, five pairs of mRNA sequences for different genes were compared in species that had diverged at the same time. The evolutionary rate of synonymous substitution was estimated to be 5.1 X 10(-9) per site per year on the average and is approximately constant among different genes. It also is suggested that this property would be suitable for a molecular clock to determine the evolutionary relationships and branching order of duplicated genes. Each functional block of the noncoding region evolves with a rate that is almost constant, regardless of the types of genes. The intervening sequence and the 5' portion of the 3' noncoding region show considerable divergence, the extent of which is almost comparable to that in the synonymous codon sites, whereas the other blocks consisting of the 5' noncoding region and the 3' portion of the 3' noncoding region are strongly conserved, showing approximatley half of the divergence of the synonymous sites. This strong sequence preservation might be due to the functional requirements for transcription and modification of mRNA.

Amino Acid Sequence↗
PubMed2025

Genome-wide identification and expression profiling of the MADS-box gene family in Lavandula angustifolia.

BACKGROUND: MADS-box genes encode transcription factors critical for plant development, particularly floral organogenesis, flowering time regulation, and adaptation to environmental stresses. Among these, the MIKCC-type genes are pivotal regulators in floral developmental processes. Although the evolutionary diversification and functional dynamics of MADS-box genes have been extensively characterized in model plants such as Arabidopsis thaliana and Oryza sativa, their evolutionary relationships and functional profiles in Lavandula angustifolia, an economically significant aromatic plant, remain poorly understood. RESULTS: Genome-wide analysis identified 173 MADS-box genes in L. angustifolia, categorized into type I (Mα: 26; Mβ: 0; Mγ: 10) and type II (MIKCC: 125; MIKC*: 12) based on phylogenetic comparisons with A. thaliana. The MIKCC subgroup was further subdivided into 12 subclasses, including genes central to the ABCDE model of floral organ specification. Structural analyses revealed distinct conserved motifs and exon-intron configurations specific to each subgroup, indicative of functional divergence. Synteny analysis demonstrated Whole Genome Duplication (WGD) and segmental duplications as major contributors to MIKCC gene family expansion, notably among genes linked to floral organ development. Expression profiling via RNA-seq and quantitative real-time PCR (qPCR) showed type II MADS-box genes exhibited higher expression levels with pronounced tissue-specific and developmental stage-specific expression patterns compared to type I genes. Many type II genes displayed significant associations with floral organogenesis, floral transition, and abiotic stress responses, underscoring their essential roles in reproductive development and environmental adaptability in L. angustifolia. CONCLUSIONS: The identification and comprehensive characterization of 173 MADS-box genes in L. angustifolia highlight the significant expansion of the MIKCC subgroup driven primarily by WGD and segmental duplications. The distinct structural features and specific expression patterns observed provide insights into the functional divergence and complexity of these genes, particularly regarding floral organogenesis and adaptation to environmental stress. This study establishes a robust molecular basis for further functional analysis and genetic improvement of aromatic plants.

MADS Domain Proteins↗
PubMed1985

Nucleotide sequence divergence and functional constraint in VIP precursor mRNA evolution between human and rat.

The nucleotide sequence analysis of cloned cDNA for VIP precursor from rat cerebral cortex reveals that the precursor contains both rat VIP and PHI-27. The deduced primary structure of rat VIP is identical with human VIP. The amino acid sequence of rat PHI-27 differs by 4 amino acids from human PHM-27. When each VIP precursor is divided functionally into 6 domains, the amino acid sequence homology between rat and human precursors ranges from 69 to 100%. In contrast, any domain exhibits an essentially equal degree of nucleotide sequence homology.

Amino Acid Sequence↗
PubMed1991

Predicting outcome following pulmonary resection in cystic fibrosis patients.

A small subset of cystic fibrosis (CF) patients develop pulmonary disease primarily limited to one lobe or lung segment requiring prolonged recurrent hospitalizations with intensive medical therapy. Although surgery has been advocated for patients who do not respond to medical therapy, very little is known about criteria for selection of patients who might benefit from resection of the involved parenchyma. In an attempt to further define criteria for pulmonary resection in these patients, we retrospectively reviewed our experience at Tulane Medical Center over the past 10 years. Fourteen patients with CF, ranging from 3 to 30 years of age, underwent 17 pulmonary resections. Indications for surgery were persistent lobar or pulmonary atelectasis and bronchiectasis requiring multiple hospitalizations and unresponsive to medical therapy (n = 13), bronchopleural fistula (n = 2), or hemoptysis not responding to medical therapy or selective embolization (n = 2). Thirteen lobectomies and four pneumonectomies were performed. Only two resections were on the left side and 11 right upper lobectomies were performed. Postoperative hospitalization ranged from 5 to 21 days (mean, 8.5 days). Preoperative pulmonary function tests showed widely divergent function in these patients. Forced expiratory volume (FEV1) ranged from 11% to 88% whereas forced vital capacity (FVC) ranged from 20% to 100% of predicted values. Oxygen saturation ranged from 86% to 99%. Although there was no significant difference in preoperative and postoperative FVC or O2 saturation, there was a significant (P less than .003) decrease in the postoperative FEV1. In the 12 surviving patients followed for at least 1 year, there was also a significant reduction (P less than .001) in the number of hospitalizations required due to pulmonary exacerbations from an average 2.2 admissions per year (range, 0.44 to 3.5 admissions per year) to 1.1 admissions per year (range, 0 to 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗