Mammalian Gene Family Research Articles

Fc gamma receptors: Their evolution, genomic architecture, genetic variation, and impact on human disease.

Fc gamma receptors (FcγRs) are a family of receptors that bind IgG antibodies and interface at the junction of humoral and innate immunity. Precise regulation of receptor expression provides the necessary balance to achieve healthy immune homeostasis by establishing an appropriate immune threshold to limit autoimmunity but respond effectively to infection. The underlying genetics of the FCGR gene family are central to achieving this immune threshold by regulating affinity for IgG, signaling efficacy, and receptor expression. The FCGR gene locus was duplicated during evolution, retaining very high homology and resulting in a genomic region that is technically difficult to study. Here, we review the recent evolution of the gene family in mammals, its complexity and variation through copy number variation and single-nucleotide polymorphism, and impact of these on disease incidence, resolution, and therapeutic antibody efficacy. We also discuss the progress and limitations of current approaches to study the region and emphasize how new genomics technologies will likely resolve much of the current confusion in the field. This will lead to definitive conclusions on the impact of genetic variation within the FCGR gene locus on immune function and disease.

The CATERPILLERS.

This Pillars of Immunology article is a commentary on “Cutting Edge: CATERPILLER: A large family of mammalian genes containing CARD, pyrin, nucleotide-binding, and leucine-rich repeat domains,” a pivotal article written by J. A. Harton, M. W. Linhoff, J. Zhang, and J. P.-Y. Ting,” and published in The Journal of Immunology, in 2002. https://doi.org/10.4049/jimmunol.169.8.4088.

Circadian gene Per3 promotes astroblastoma progression through the P53/BCL2/BAX signalling pathway

The key circadian genes, Period1(Per1), Period2(Per2), and Period3(Per3), constitute the mammalian Period gene family. The abnormal expression of Per1 and Per2 is closely related to tumor development, but there are few reports on Per3 and tumorigenesis. This study was conducted to determine whether the abnormal expression of Per3 could influence the progression of astroblastoma. The results indicated that the expression level of Per3 was increased in astroblastoma cells, and the high expression of Per3 was correlated with the poor overall survival time of glioma patients. The role of Per3 in astroblastoma cells was then investigated using two approaches: interference and overexpression. The interference of Per3 inhibited astroblastoma cell proliferation by inducing the cell cycle at the S phase. The interference of Per3 inhibited the migration and invasion of astroblastoma cells, while promoted the astroblastoma cell apoptosis and the expression of the apoptosis genes Cleaved-CASP3, P53, and BAX. The overexpression of Per3 promoted proliferation by affecting the S phase distribution of the astroblastoma cell cycle. The overexpression of Per3 promoted the migration and invasion of astroblastoma cells, while inhibited the astroblastoma cell apoptosis and the expression of apoptosis genes Cleaved-CASP3, P53, and BAX. RNA-seq analysis showed that the interference of Per3 in astrocytoma cells resulted in significant changes in the expression levels of 764 genes. Among the differentially expressed genes enriched in apoptosis-related pathways, the interference of Per3 resulted in significant upregulation of MARCKSL1 expression, in contrast to significant downregulation of SFRP4, EPB41L3, and GPC5 expression. Taken together, our results suggest that Per3 appears to be a pro-cancer gene by altering the proliferation, migration, invasion, and apoptosis of astroblastoma cells. As a result, the Per3 gene may be a promising therapeutic target in the treatment of astroblastoma.

The expression of Nramp1 modulates the uptake of Mycobacterium tuberculosis by macrophages through alternating inflammatory responses

Natural-resistance-associated macrophage protein-1 (NRAMP1) is a transmembrane protein of the mammalian SLC11 gene family. Previously, genome-wide association study (GWAS) have shown that the single nucleotide polymorphisms (SNPs) of NRAMP1 are associated with human susceptibility to tuberculosis (TB), and the detection of clinical samples have demonstrated that the expression levels of NRAMP1 are concomitant with the susceptibility to TB in humans and cows, but underlying mechanism is unknown. In this study, we completed a series of experiments to investigate how the expression of Nramp1 affects the infection of macrophages with Mycobacterium tuberculosis (Mtb). We found that the increase of Nramp1 expression induced the decrease of Mtb infection efficiency and the higher-level expression of pro-inflammatory cytokines and chemokines, However, the knockdown of Nramp1 promoted the efficiency of bacilli infection to macrophages and induced lower-levels of expression of pro-inflammatory cytokines and chemokines. Collectively, the results in this study demonstrated that the levels of Nramp1 expression affect Mtb infection of macrophage and regulate pro-inflammatory responses of macrophages to Mtb infection, indicating the population with the low-expression level of NRAMP1 predispose to Mtb infection and TB development, and suggesting SNPs in NRAMP1 modulate the host susceptibility to TB through its regulation of NRAMP1 expression.

Expression signature and prognostic value of CREC gene family in human colorectal cancer

Colorectal cancer (CRC) is one of the malignant tumors with the highest morbidity and mortality and poor prognosis. The mammalian gene family of Cab45/reticulocalbin/ERC-45/calumenin (CREC) consists of RCN1, RCN2, RCN3, SDF4 and CALU. Although CREC family members have been associated with CRC, the expression pattern, prognostic value, and the role of CREC family in CRC remain unclear. In this study, the expression, survival and biological functions of CREC family in CRC were determined via bioinformatic datasets analysis and experimental verification on clinical CRC specimen. Bioinformatic analysis showed that the expression levels of most CREC family genes were higher in CRC tissues than in normal colorectal tissues. The qPCR and western blot results also revealed that the transcriptional and protein levels of CREC family were elevated in CRC tissues compared with adjacent tissues. Besides, CREC family was significantly correlated with advanced tumor stage and poor prognosis of CRC patients. The expression levels of CREC family had correlations with genomic mutation and methylation, and with the infiltration levels of CD4 + T cells, macrophages, neutrophils, and dendritic cells in the microenvironment of CRC. Functional networks enrichment analysis indicated that the genes of CREC family were essential factors for CRC metastasis. Collectively, these findings suggest that CREC family might be potential targets for the treatment of CRC and candidate prognostic markers for CRC patients.

The NLR gene family: from discovery to present day.

The mammalian NLR gene family was first reported over 20 years ago, although several genes that were later grouped into the family were already known at that time. Although it is widely known that NLRs include inflammasome receptors and/or sensors that promote the maturation of caspase 1, IL-1β, IL-18 and gasdermin D to drive inflammation and cell death, the other functions of NLR family members are less well appreciated by the scientific community. Examples include MHC class II transactivator (CIITA), a master transcriptional activator of MHC class II genes, which was the first mammalian NBD-LRR-containing protein to be identified, and NLRC5, which regulates the expression ofMHC class I genes. Other NLRs govern key inflammatory signalling pathways or interferon responses, and several NLR family members serve as negative regulators of innate immune responses. Multiple NLRs regulate the balance of cell death, cell survival, autophagy, mitophagy and even cellular metabolism. Perhaps the least discussed group of NLRs are those with functions in the mammalian reproductive system. The focus of this Review is to provide a synopsis of the NLR family, including both the intensively studied and the underappreciated members. We focus on the function, structure and disease relevance of NLRs and highlight issues that have received less attention in the NLR field. We hope this may serve as an impetus for future research on the conventional and non-conventional roles of NLRs within and beyond the immune system.

Effects of the Zbtb1 Gene on Chromatin Spatial Structure and Lymphatic Development: Combined Analysis of Hi-C, ATAC-Seq and RNA-Seq

Zbtb1 (zinc finger and BTB domain containing 1) is a member of mammalian zbtb gene family. A series of bioinformatics analysis was carried out for the EL4 cell and the Zbtb1-deficient EL4 cell by Hi-C, ATAC-seq and RNA-seq techniques. Finally, Hi-C results showed that the intensity of chromatin interaction in the deletion group decreased with distance, the degree of chromosome interaction decreased significantly, the AB division region changed significantly, and the compactness of TAD structure decreased; The results of ATAC-seq showed that the open area and degree of chromatin in the deletion group decreased; 7778 differentially expressed mRNAs were found by RNA-seq. Our experimental results for the first time expounded the significance of Zbtb1 gene for T cell development, lymphocyte production and apoptosis from the aspects of chromosome spatial structure and chromatin opening degree, and provided relevant theoretical basis and data support for the in-depth study of related Zbtb1 genes in the future.

Manipulating Galectin Expression in Zebrafish (Danio rerio).

Techniques for disrupting gene expression are invaluable tools for the analysis of the biological role of a gene product. Because of its genetic tractability and multiple advantages over conventional mammalian models, the zebrafish (Danio rerio) is recognized as a powerful system for gaining new insight into diverse aspects of human health and disease. Among the multiple mammalian gene families for which the zebrafish has shown promise as an invaluable model for functional studies, the galectins have attracted great interest due to their participation in early development, regulation of immune homeostasis, and recognition of microbial pathogens. Galectins are β-galactosyl-binding lectins with a characteristic sequence motif in their carbohydrate recognition domains (CRDs), that constitute an evolutionary conserved family ubiquitous in eukaryotic taxa. Galectins are emerging as key players in the modulation of many important pathological processes, which include acute and chronic inflammatory diseases, autoimmunity and cancer, thus making them potential molecular targets for innovative drug discovery. Here, we provide a review of the current methods available for the manipulation of gene expression in the zebrafish, with a focus on gene knockdown [morpholino (MO)-derived antisense oligonucleotides] and knockout (CRISPR-Cas) technologies.

MicroRNA and circRNA Expression Analysis in a Zbtb1 Gene Knockout Monoclonal EL4 Cell Line.

Zinc finger and BTB domain containing 1(Zbtb1) is a transcriptional suppressor protein, and a member of the mammalian Zbtb gene family. Previous studies have shown that Zbtb1 is essential for T-cell development. However, the role of Zbtb1 in T-cell lymphoma is undetermined. In this study, an EL4 cell line with Zbtb1 deletion was constructed using the CRISPR-Cas9 technique. The expression profiles of microRNA and circRNA produced by the control and gene deletion groups were determined by RNA-seq. In general, 24 differentially expressed microRNA and 16 differentially expressed circRNA were found between normal group and gene deletion group. Through further analysis of differentially expressed genes, GO term histogram and KEGG scatter plot were drawn, and three pairs of miRNA and circRNA regulatory relationships were found. This study describes the differentially expressed microRNA and circRNA in normal and Zbtb1-deficient EL4 cell lines, thus providing potential targets for drug development and clinical treatment of T-cell lymphoma.

Oxidative stress drives divergent evolution of the glutathione peroxidase (GPX) gene family in mammals.

The molecular basis for adaptations to extreme environments can now be understood by interrogating the ever-increasing number of sequenced genomes. Mammals such as cetaceans, bats, and highland species can protect themselves from oxidative stress, a disruption in the balance of reactive oxygen species, which results in oxidative injury and cell damage. Here, we consider the evolution of the glutathione peroxidase (GPX) family of antioxidant enzymes by interrogating publicly available genome data from 70 mammalian species from all major clades. We identified 8 GPX subclasses ubiquitous to all mammalian groups. Mammalian GPX gene families resolved into the GPX4/7/8 and GPX1/2/3/5/6 groups and are characterized by several instances of gene duplication and loss, indicating a dynamic process of gene birth and death in mammals. Seven of the eight GPX subfamilies (all but GPX7) were under positive selection, with the residues under selection located at or close to active sites or at the dimer interface. We also reveal evidence of a correlation between ecological niches (e.g. high oxidative stress) and the divergent selection and gene copy number of GPX subclasses. Notably, a convergent expansion of GPX1 was observed in several independent lineages of mammals under oxidative stress and may be important for avoiding oxidative damage. Collectively, this study suggests that the GPX gene family has shaped the adaption of mammals to stressful environments.

Expression Patterns and Prognostic Values of ORMDL1 in Different Cancers

The mammalian orosomucoid-like gene family (ORMDL), containing ORMDL1, ORMDL2, and ORMDL3, is the important regulator of sphingolipid metabolism, which is relevant to cell growth, proliferation, migration, and invasion. Since the role of ORMDL1 in cancers remained unclear, the main purpose of our study was to explore the expression patterns and prognostic values of ORMDL1 in different tumors, especially in cholangiocarcinoma (CHOL), lymphoid neoplasm diffuse large B cell lymphoma (DLBCL), acute myeloid leukemia (LAML), and thymoma (THYM). Bioinformatics tools including GEPIA, CCLE, LinkedOmics, cBioPortal, and TIMER databases were used. As a result, the expression levels of ORMDL1 in tumor tissues and normal tissues varied in different cancers, especially significantly upregulated in CHOL, DLBCL, LAML, and THYM. Moreover, ORMDL1 mRNA was also highly expressed in cell lines of DLBCL and LAML. Further studies showed that ORMDL1 overexpression was associated with poor prognosis in DLBCL, but not significant in CHOL, LAML, and THYM. Consistently, there were genetic alterations of ORMDL1 in DLBCL, and patients with genetic alterations indicated worse survival. Coexpressed genes and related biological events with ORMDL1 in DLBCL were found via LinkedOmics, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The relationship between ORMDL1 and cancer immune cells was investigated, and ORMDL1 expression was positively correlated with infiltrating levels of B cells. In conclusion, ORMDL1 is suggested to be a tumorigenic factor and considered as the potential therapeutic target and prognostic biomarker in DLBCL.

Convergent degeneration of olfactory receptor gene repertoires in marine mammals

BackgroundOlfactory receptors (ORs) can bind odor molecules and play a crucial role in odor sensation. Due to the frequent gains and losses of genes during evolution, the number of OR members varies greatly among different species. However, whether the extent of gene gains/losses varies between marine mammals and related terrestrial mammals has not been clarified, and the factors that might underlie these variations are unknown.ResultsTo address these questions, we identified more than 10,000 members of the OR family in 23 mammals and classified them into 830 orthologous gene groups (OGGs) and 281 singletons. Significant differences occurred in the number of OR repertoires and OGGs among different species. We found that all marine mammals had fewer OR genes than their related terrestrial lineages, with the fewest OR genes found in cetaceans, which may be closely related to olfactory degradation. ORs with more gene duplications or loss events tended to be under weaker purifying selection. The average gain and loss rates of OR genes in terrestrial mammals were higher than those of mammalian gene families, while the average gain and loss rates of OR genes in marine mammals were significantly lower and much higher than those of mammalian gene families, respectively. Additionally, we failed to detect any one-to-one orthologous genes in the focal species, suggesting that OR genes are not well conserved among marine mammals.ConclusionsMarine mammals have experienced large numbers of OR gene losses compared with their related terrestrial lineages, which may result from the frequent birth-and-death evolution under varied functional constrains. Due to their independent degeneration, OR genes present in each lineage are not well conserved among marine mammals. Our study provides a basis for future research on the olfactory receptor function in mammals from the perspective of evolutionary trajectories.

Msx Homeobox Genes Act Downstream of BMP2 to Regulate Endometrial Decidualization in Mice and in Humans.

Endometrial stromal cells differentiate to form decidual cells in a process known as decidualization, which is critical for embryo implantation and successful establishment of pregnancy. We previously reported that bone morphogenetic protein 2 (BMP2) mediates uterine stromal cell differentiation in mice and in humans. To identify the downstream target(s) of BMP2 signaling during decidualization, we performed gene-expression profiling of mouse uterine stromal cells, treated or not treated with recombinant BMP2. Our studies revealed that expression of Msx2, a member of the mammalian Msx homeobox gene family, was markedly upregulated in response to exogenous BMP2. Interestingly, conditional ablation of Msx2 in the uterus failed to prevent a decidual phenotype, presumably because of functional compensation of Msx2 by Msx1, a closely related member of the Msx family. Indeed, in Msx2-null uteri, the level of Msx1 expression in the stromal cells was markedly elevated. When conditional, tissue-specific ablation of both Msx1 and Msx2 was accomplished in the mouse uterus, a dramatically impaired decidual response was observed. In the absence of both Msx1 and Msx2, uterine stromal cells were able to proliferate, but they failed to undergo terminal differentiation. In parallel experiments, addition of BMP2 to human endometrial stromal cell cultures led to a robust enhancement of MSX1 and MSX2 expression and stimulated the differentiation process. Attenuation of MSX1 and MSX2 expression by small interfering RNAs greatly reduced human stromal differentiation in vitro, indicating a conservation of their roles as key mediators of BMP2-induced decidualization in mice and women.

Sestrin2 Supports Lung Tumor Growth in Early Stages of Cancer Development in Mice but Might Play a Tumor Suppressive Role in the Late Stages of Carcinogenesis

The goal of this study was to understand the role of the p53‐inducible SESN1 and SESN2 genes in the development of lung cancer. Our studies are based on the development of mouse models employing inducible activation of the Kras oncogene in mice deficient for Sesn1 or Sesn2 genes. These mice develop lung cancers in response to injection with Adeno‐Cre virus.The members of the mammalian Sestrin gene family (SESN1, SESN2 and SESN3) encode evolutionary conserved proteins called sestrins that play an important role in regulating cell viability and metabolism in response to stress. The major activity of Sestrins is modulation of mammalian target of rapamycin complexes 1 and 2 (mTORC1/2), which are responsible for regulation of cell growth, metabolism, autophagy and viability. Strikingly, two of three members of the mammalian sestrin family, i.e. SESN1 and SESN2, are targets of transcription factor p53 which plays a major role in tumor suppression. We found that both SESN1 and SESN2 genes are downregulated in the majority of human lung cancers. Therefore, we proposed that SESN1 and SESN2 might be responsible for tumor suppressive activities of p53. However, inactivation of a single Sesn2 gene or both Sesn1 and Sesn2 genes did not affect the number of tumors in mice. Moreover, we observed that Sestrin2‐positive tumors were larger, indicating that Sestrin2 supports tumor growth during early stages of lung carcinogenesis. These effects correlated with higher activity of AKT kinase in the Sestrin2‐proficient mice as compared to Sestrin2‐deficient counterparts. Being a major regulator of cell growth and proliferation, AKT can be a critical target of Sestrin2 in regulating of tumor growth. Nevertheless, we have also demonstrated that silencing of Sestrin2 in human lung adenocarcinoma cells accelerates growth of tumor xenografts in nude mice and provides resistance to anticancer genotoxic drugs.Therefore, we conclude that Sestrin2 support tumor growth at early stages of cancer development, but might suppress carcinogenesis in the late stages. Moreover, tumors with low expression of Sestrin2 may be selected during chemo‐ and radiotherapy.Support or Funding InformationThe studies were supported by the Grant 17‐14‐01420 from the Russian Science Foundation to AB and NCI CA172660 to SG.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Olfactory receptors expressed in various non-olfactory tissues.

Olfactory receptor(OR)genes constitute the largest gene family in mammals. Some of them have been shown to be expressed not only in the olfactory system, but also in various non-olfactory tissues. So far, the roles of such ectopically expressed ORs have been suggested mainly by in vitro experiments using cultured cells or tissues. Recently, analyses using OR knockout mice have revealed a few examples of important physiological functions outside the olfactory epithelium. An OR expressed in the carotid body senses the hypoxia and regulates breathing. An OR expressed in enterochromaffin(EC)cells in the gut senses microbial metabolites and induces a serotonin release to modulate serotonin-sensitive primary afferent neurons. These results suggest that ectopically expressed ORs sense an internal environmental change through chemical cues and modulate physiologically significant functions specific to each tissue where an OR is expressed. Further work will be required to understand their roles in other tissues.

Evolution of Trichocyte Keratin Associated Proteins.

The major components of hair are keratins and keratin associated proteins (KRTAPs). KRTAPs form the interfilamentous matrix between intermediate filament bundles through extensive disulfide bond cross-linking with the numerous cysteine residues in hair keratins. A variable number of approximately100-180 genes compose the KRTAP gene family in mammals. KRTAP gene family members present a typical pattern of concerted evolution, and its evolutionary features are consistent with the evolution of mammalian hair. KRATP genes might be more important in determining the structure of cashmere fibers in domestic mammals like sheep and goats. KRTAP gene variants thus should provide information for improved wool by sheep and goat breeding.

Aligning coding sequences with frameshift extension penalties

BackgroundFrameshift translation is an important phenomenon that contributes to the appearance of novel coding DNA sequences (CDS) and functions in gene evolution, by allowing alternative amino acid translations of gene coding regions. Frameshift translations can be identified by aligning two CDS, from a same gene or from homologous genes, while accounting for their codon structure. Two main classes of algorithms have been proposed to solve the problem of aligning CDS, either by amino acid sequence alignment back-translation, or by simultaneously accounting for the nucleotide and amino acid levels. The former does not allow to account for frameshift translations and up to now, the latter exclusively accounts for frameshift translation initiation, not considering the length of the translation disruption caused by a frameshift.ResultsWe introduce a new scoring scheme with an algorithm for the pairwise alignment of CDS accounting for frameshift translation initiation and length, while simultaneously considering nucleotide and amino acid sequences. The main specificity of the scoring scheme is the introduction of a penalty cost accounting for frameshift extension length to compute an adequate similarity score for a CDS alignment. The second specificity of the model is that the search space of the problem solved is the set of all feasible alignments between two CDS. Previous approaches have considered restricted search space or additional constraints on the decomposition of an alignment into length-3 sub-alignments. The algorithm described in this paper has the same asymptotic time complexity as the classical Needleman–Wunsch algorithm.ConclusionsWe compare the method to other CDS alignment methods based on an application to the comparison of pairs of CDS from homologous human, mouse and cow genes of ten mammalian gene families from the Ensembl-Compara database. The results show that our method is particularly robust to parameter changes as compared to existing methods. It also appears to be a good compromise, performing well both in the presence and absence of frameshift translations. An implementation of the method is available at https://github.com/UdeS-CoBIUS/FsePSA.

Population genetics of mouse lemur vomeronasal receptors: current versus past selection and demographic inference

BackgroundA major effort is underway to use population genetic approaches to identify loci involved in adaptation. One issue that has so far received limited attention is whether loci that show a phylogenetic signal of positive selection in the past also show evidence of ongoing positive selection at the population level. We address this issue using vomeronasal receptors (VRs), a diverse gene family in mammals involved in intraspecific communication and predator detection. In mouse lemurs, we previously demonstrated that both subfamilies of VRs (V1Rs and V2Rs) show a strong signal of directional selection in interspecific analyses. We predicted that ongoing sexual selection and/or co-evolution with predators may lead to current directional or balancing selection on VRs. Here, we re-sequence 17 VRs and perform a suite of selection and demographic analyses in sympatric populations of two species of mouse lemurs (Microcebus murinus and M. ravelobensis) in northwestern Madagascar.ResultsM. ravelobensis had consistently higher genetic diversity at VRs than M. murinus. In general, we find little evidence for positive selection, with most loci evolving under purifying selection and one locus even showing evidence of functional loss in M. ravelobensis. However, a few loci in M. ravelobensis show potential evidence of positive selection. Using mismatch distributions and expansion models, we infer a more recent colonisation of the habitat by M. murinus than by M. ravelobensis, which most likely speciated in this region earlier on.ConclusionsThese findings suggest that the analysis of VR variation is useful in inferring demographic and phylogeographic history of mouse lemurs. In conclusion, this study reveals a substantial heterogeneity over time in selection on VR loci, suggesting that VR evolution is episodic.

Coordinated shift of olfactory amino acid responses and V2R expression to an amphibian water nose during metamorphosis.

All olfactory receptors identified in teleost fish are expressed in a single sensory surface, whereas mammalian olfactory receptor gene families segregate into different olfactory organs, chief among them the main olfactory epithelium expressing ORs and TAARs, and the vomeronasal organ expressing V1Rs and V2Rs. A transitional stage is embodied by amphibians, with their vomeronasal organ expressing more 'modern', later diverging V2Rs, whereas more 'ancient', earlier diverging V2Rs are expressed in the main olfactory epithelium. During metamorphosis, the main olfactory epithelium of Xenopus tadpoles transforms into an air-filled cavity (principal cavity, air nose), whereas a newly formed cavity (middle cavity) takes over the function of a water nose. We report here that larval expression of ancient V2Rs is gradually lost from the main olfactory epithelium as it transforms into the air nose. Concomitantly, ancient v2r gene expression begins to appear in the basal layers of the newly forming water nose. We observe the same transition for responses to amino acid odorants, consistent with the hypothesis that amino acid responses may be mediated by V2R receptors.

Evolution and Distribution of Teleost myomiRNAs: Functionally Diversified myomiRs in Teleosts.

Myosin heavy chain (MYH) genes belong to a multigene family, and the regulated expression of each member determines the physiological and contractile muscle properties. Among these, MYH6, MYH7, and MYH14 occupy unique positions in the mammalian MYH gene family because of their specific expression in slow/cardiac muscles and the existence of intronic micro(mi) RNAs. MYH6, MYH7, and MYH14 encode miR-208a, miR-208b, and miR-499, respectively. These MYH encoded miRNAs are designated as myomiRs because of their muscle-specific expression and functions. In mammals, myomiRs and host MYHs form a transcription network involved in muscle fiber-type specification; thus, genomic positions and expression patterns of them are well conserved. However, our previous studies revealed divergent distribution and expression of MYH14/miR-499 among teleosts, suggesting the unique evolution of myomiRs and host MYHs in teleosts. Here, we examined distribution and expression of myomiRs and host MYHs in various teleost species. The major cardiac MYH isoforms in teleosts are an intronless gene, atrial myosin heavy chain (amhc), and ventricular myosin heavy chain (vmhc) gene that encodes an intronic miRNA, miR-736. Phylogenetic analysis revealed that vmhc/miR-736 is a teleost-specific myomiR that differed from tetrapoda MYH6/MYH7/miR-208s. Teleost genomes also contain species-specific orthologs in addition to vmhc and amhc, indicating complex gene duplication and gene loss events during teleost evolution. In medaka and torafugu, miR-499 was highly expressed in slow/cardiac muscles whereas the expression of miR-736 was quite low and not muscle specific. These results suggest functional diversification of myomiRs in teleost with the diversification of host MYHs.