Orthologous Counterparts Research Articles

Dynamic gene expression pattern in zebrafish gall bladder - an experimental study

Gall bladder cancer (GBC) is one of the common biliary tract malignancies that is often associated with late presentation of clinical symptoms resulting in poor prognosis, thereby considerably increasing the mortality rate. Geographic and ethnic variations are one of the major causes of GBC incidence. However, in addition to genetic susceptibility to GBC, other factors like age, obesity, gender, and exposure to certain heavy chemicals may also lead to the incidence of GBC. Most of GBC research has so far used traditional cell culture systems. Recently, newer approaches using 2D and 3D cultures, xenograft models, and organoids are also becoming popular. However, whole organism model systems for GBC research have not yet been established. In this study, we propose the use of zebrafish as a model organism to study GBC. However, the zebrafish gall bladder is relatively unexplored besides the anatomical features. Here, we unravel and then compare the unique transcriptomic profile of zebrafish gall bladder with humans to identify genes consistently expressed in both species. We provide a comprehensive list of all gall bladder specific genes in zebrafish that also have their orthologous counterparts in humans. Therefore, they can be used as potential biomarkers for gall bladder transcriptomic profile. To the best of our knowledge, this is the only study so far to provide a complete genomic expression profile of zebrafish gall bladder along with an exhaustive cross-species comparison, thus paving the path for using zebrafish as a model organism to study GBC and help identify novel biomarkers for its early detection and diagnosis.

Conserved and unique features of pepper FLOWERING LOCUS T-like genes revealed by comparative analysis among solanaceous crops

FLOWERING LOCUS T (FT)-like genes play crucial and antagonistic roles in flowering induction in plants. We analyzed the functional and evolutionary characteristics of pepper FT-like genes. According to their similarity to an FT ortholog of tomato, 10 phosphatidylethanolamine-binding protein family genes were retrieved from the pepper genome. Phylogenetic analysis placed the proteins encoded by six of these genes (CaFT1–CaFT6) into an FT-like clade. Comparative genomic analysis showed that four of pepper FT-like genes (CaFT1, CaFT2, CaFT3, CaFT4) have orthologous counterparts in other three solanaceous crops (tomato, potato, and tobacco). CaFT5, which is unique to pepper, was inferred to have arisen by genomic rearrangement followed by duplication of CaFT2. Interestingly, CaFT6, which has been nominated as a pepper FT ortholog, was located in a genomic region not syntenic to the loci of FT orthologs in other crops and was clustered with two other FT-like genes. This result implies the involvement of a unique evolutionary process in the origin of CaFT6. Pepper FT-like genes were mostly expressed in leaves, and their protein products interacted with FLOWERING LOCUS D. When they were overexpressed in Arabidopsis, flowering was promoted by two genes (CaFT6 and CaFT4) and delayed by two others (CaFT1 and CaFT3). The expressions of CaFT6 and CaFT4 were also negatively related to flowering time in pepper accessions implying that they act as flowering promoter genes. The conserved and unique characteristics of pepper FT-like genes provide insights into the dynamic evolution of FT-like genes and useful information for manipulation of FT-like genes to improve the productivity.

New insights into natural rubber biosynthesis from rubber-deficient lettuce mutants expressing goldenrod orguayule cis-prenyltransferase.

Lettuce produces natural rubber (NR) with an average Mw of > 1 million Da in laticifers, similar to NR from rubber trees. As lettuce is an annual, self-pollinating, and easily transformable plant, it is an excellent model for molecular genetic studies of NR biosynthesis. CRISPR/Cas9 mutagenesis was optimized using lettuce hairy roots, and NR-deficient lettuce was generated via bi-allelic mutations in cis-prenyltransferase (CPT). This is the first null mutant of NR deficiency in plants. In the CPT mutant, orthologous CPT counterparts from guayule (Parthenium argentatum) and goldenrod (Solidago canadensis) were expressed under a laticifer-specific promoter to examine how the average Mw of NR is affected. No developmental defects were observed in the NR-deficient mutants. The lettuce mutants expressing guayule and goldenrod CPT produced 1.8 and 14.5 times longer NR, respectively, than the plants of their origin. This suggests that, although goldenrod cannot synthesize a sufficiently lengthy NR, goldenrod CPT has the catalytic competence to produce high-quality NR in the cellular context of lettuce laticifers. Thus, CPT alone does not determine the length of NR. Other factors, such as substrate concentration, additional proteins, and/or the nature of protein complexes including CPT-binding proteins, influence CPT activity in determining NR length.

Genome-Wide Identification and Expression Analysis of the R2R3-MYB Transcription Factor Family Revealed Their Potential Roles in the Flowering Process in Longan (Dimocarpus longan).

Longan (Dimocarpus longan Lour.) is a productive fruit crop with high nutritional and medical value in tropical and subtropical regions. The MYB gene family is one of the most widespread plant transcription factor (TF) families participating in the flowering regulation. However, little is known about the MYB TFs involved in the flowering process in longan and its regulatory network. In this study, a total of 119 DlR2R3-MYB genes were identified in the longan genome and were phylogenetically grouped into 28 subgroups. The groupings were supported by highly conserved gene structures and motif composition of DlR2R3-MYB genes in each subgroup. Collinearity analysis demonstrated that segmental replications played a more crucial role in the expansion of the DlR2R3-MYB gene family compared to tandem duplications, and all tandem/segmental duplication gene pairs have evolved under purifying selection. Interspecies synteny analysis among longan and five representative species implied the occurrence of gene duplication events was one of the reasons contributing to functional differentiation among species. RNA-seq data from various tissues showed DlR2R3-MYB genes displayed tissue-preferential expression patterns. The pathway of flower development was enriched with six DlR2R3-MYB genes. Cis-acting element prediction revealed the putative functions of DlR2R3-MYB genes were related to the plant development, phytohormones, and environmental stresses. Notably, the orthologous counterparts between Arabidopsis and longan R2R3-MYB members tended to play conserved roles in the flowering regulation and stress responses. Transcriptome profiling on off-season flower induction (FI) by KClO3 indicated two up-regulated and four down-regulated DlR2R3-MYB genes involved in the response to KClO3 treatment compared with control groups. Additionally, qRT-PCR confirmed certain genes exhibited high expression in flowers/flower buds. Subcellular localization experiments revealed that three predicted flowering-associated MYB proteins were localized in the nucleus. Future functional studies on these potential candidate genes involved in the flowering development could further the understanding of the flowering regulation mechanism.

Natural variation in OsGASR7 regulates grain length in rice.

Natural variation in OsGASR7 regulates grain length in rice.

Revisiting the Role of Transcription Factors in Coordinating the Defense Response Against Citrus Bark Cracking Viroid Infection in Commercial Hop (Humulus Lupulus L.).

Transcription factors (TFs) play a major role in controlling gene expression by intricately regulating diverse biological processes such as growth and development, the response to external stimuli and the activation of defense responses. The systematic identification and classification of TF genes are essential to gain insight into their evolutionary history, biological roles, and regulatory networks. In this study, we performed a global mining and characterization of hop TFs and their involvement in Citrus bark cracking viroid CBCVd infection by employing a digital gene expression analysis. Our systematic analysis resulted in the identification of a total of 3,818 putative hop TFs that were classified into 99 families based on their conserved domains. A phylogenetic analysis classified the hop TFs into several subgroups based on a phylogenetic comparison with reference TF proteins from Arabidopsis thaliana providing glimpses of their evolutionary history. Members of the same subfamily and subgroup shared conserved motif compositions. The putative functions of the CBCVd-responsive hop TFs were predicted using their orthologous counterparts in A. thaliana. The analysis of the expression profiling of the CBCVd-responsive hop TFs revealed a massive differential modulation, and the expression of the selected TFs was validated using qRT-PCR. Together, the comprehensive integrated analysis in this study provides better insights into the TF regulatory networks associated with CBCVd infections in the hop, and also offers candidate TF genes for improving the resistance in hop against viroids.

Subtractive Genomics, Molecular Docking and Molecular Dynamics Simulation Revealed LpxC as a Potential Drug Target Against Multi-Drug Resistant Klebsiella pneumoniae

The emergence and dissemination of pan drug resistant clones of Klebsiella pneumoniae are great threat to public health. In this regard new therapeutic targets must be highlighted to pave the path for novel drug discovery and development. Subtractive proteomic pipeline brought forth UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase (LpxC), a Zn+2 dependent cytoplasmic metalloprotein and catalyze the rate limiting deacetylation step of lipid A biosynthesis pathway. Primary sequence analysis followed by 3-dimensional (3-D) structure elucidation of the protein led to the detection of K. pneumoniae LpxC (KpLpxC) topology distinct from its orthologous counterparts in other bacterial species. Molecular docking study of the protein recognized receptor antagonist compound 106, a uridine-based LpxC inhibitory compound, as a ligand best able to fit the binding pocket with a Gold Score of 67.53. Molecular dynamics simulation of docked KpLpxC revealed an alternate binding pattern of ligand in the active site. The ligand tail exhibited preferred binding to the domain I residues as opposed to the substrate binding hydrophobic channel of subdomain II, usually targeted by inhibitory compounds. Comparison with the undocked KpLpxC system demonstrated ligand induced high conformational changes in the hydrophobic channel of subdomain II in KpLpxC. Hence, ligand exerted its inhibitory potential by rendering the channel unstable for substrate binding.

O-GlcNAcase Fragment Discovery with Fluorescence Polarimetry.

The attachment of the sugar N-acetyl-D-glucosamine (GlcNAc) to specific serine and threonine residues on proteins is referred to as protein O-GlcNAcylation. O-GlcNAc transferase (OGT) is the enzyme responsible for carrying out the modification, while O-GlcNAcase (OGA) reverses it. Protein O-GlcNAcylation has been implicated in a wide range of cellular processes including transcription, proteostasis, and stress response. Dysregulation of O-GlcNAc has been linked to diabetes, cancer, and neurodegenerative and cardiovascular disease. OGA has been proposed to be a drug target for the treatment of Alzheimer's and cardiovascular disease given that increased O-GlcNAc levels appear to exert a protective effect. The search for specific, potent, and drug-like OGA inhibitors with bioavailability in the brain is therefore a field of active research, requiring orthogonal high-throughput assay platforms. Here, we describe the synthesis of a novel probe for use in a fluorescence polarization based assay for the discovery of inhibitors of OGA. We show that the probe is suitable for use with both human OGA, as well as the orthologous bacterial counterpart from Clostridium perfringens, CpOGA, and the lysosomal hexosaminidases HexA/B. We structurally characterize CpOGA in complex with a ligand identified from a fragment library screen using this assay. The versatile synthesis procedure could be adapted for making fluorescent probes for the assay of other glycoside hydrolases.

Genome-wide identification, characterization and evolution of cuticular protein genes in the malaria vector Anopheles sinensis (Diptera: Culicidae).

Thirteen cuticular protein (CP) families have been recognized in arthropods. In this study, 250 Anopheles sinensis CP genes were identified and named based on genome and transcriptome sequences. They were classified into 10 families based on motifs and phylogenetic analyses. In 11 other insect species, nine had CP numbers > 150 while Apis mellifera and Tribolium castaneum had CP numbers less than 52. The CPs of eight species occupied > 1.4% of the total genomic gene number, whereas in three species the CPs occupied < 1%. The phylogenies for each CP family in An. sinensis were constructed and discussed. The 250 CPs each had 1-8 exons with 144 CPs (57.6%) having two exons. The intron length ranged from 66-3888 bp with 174 introns (54.0%) being 66-100 bp long. Except for two CPs on two contigs, 248 CPs were mapped onto 28 scaffolds with 136 genes (54.4%) restricted to five scaffolds. A total of 107 CPs were clustered and located at 27 loci. The CPR family had the conserved motif GSYSLVEPDGTVRTV. The RR-1 subfamily had an additional 21 amino acid (aa) motifs with the YVADENGF sequence that is common in insects. The RR-2 subfamily had an additional 50 aa motifs with two additional regions RDGDVVKG and G-x(3)-VV. A comparison with 115 orthologous counterparts of An. gambiae CPs suggested purifying selection for all of these genes. This study provides basic information useful for further studies on biological functions of An. sinensis CPs as well as for comparative genomics of insect CPs.

AmphiBase: A new genomic resource for non-model amphibian species.

More than five thousand genes annotated in the recently published Xenopus laevis and Xenopus tropicalis genomes do not have a candidate orthologous counterpart in other vertebrate species. To determine whether these sequences represent genuine amphibian-specific genes or annotation errors, it is necessary to analyze them alongside sequences from other amphibian species. However, due to large genome sizes and an abundance of repeat sequences, there are limited numbers of gene sequences available from amphibian species other than Xenopus. AmphiBase is a new genomic resource covering non-model amphibian species, based on public domain transcriptome data and computational methods developed during the X. laevis genome project. Here, I review the current status of AmphiBase, including amphibian species with available transcriptome data or biological samples, and describe the challenges of building a comprehensive amphibian genomic resource in the absence of genomes. This mini-review will be informative for researchers interested in functional genomic experiments using amphibian model organisms, such as Xenopus and axolotl, and will assist in interpretation of results implicating "orphan genes." Additionally, this study highlights an opportunity for researchers working on non-model amphibian species to collaborate in their future efforts and develop amphibian genomic resources as a community.

Evolutionary fate of SVA2 elements in primate genomes

SVA (SINE/VNTR/Alu) transposable element, one of non-LTR retrotransposons, emerged in the primate genome about 25 million years ago. Currently, ~2,800 SVA copies exist in the human genome. Recently, a group of transposable elements named SVA2 is discovered. SVA2 elements share the VNTR region with the SVA element but do not contain the SINE-R region of the SVA elements. In this study, we studied the SVA2 evolution and the impact of the SVA2 elements on primate genomes. We first identified 144, 139, 136, 139, and 116 SVA2 elements in the human, chimpanzee, gorilla, orangutan, and rhesus macaque genomes, respectively. To examine the evolutionary state and structure of the elements, we performed comparative genomics, comparing human SVA2 with its orthologous counterpart from non-human primates. The result suggests that SVA2 subfamily is not, at present, retrotranspositionally active in the primate genomes because none of the SVA2 elements identified in this study are species-specific. In addition, we found that four human SVA2 elements locate in human genes and two of them have miRNA target sites, indicating that they might regulate gene expression and involve in the gene-related human diseases.

Divergence of Flowering‐Related Genes in Three Legume Species

We used a set of approximately 200 Arabidopsis thaliana (L.) Heynh. genes that are involved in the control of flowering time as a reference to identify orthologous (or homologous) counterparts of these genes in three legume species, that is, Lotus corniculatus L. var. japonicus Regel [syn. Lotus japonicus (Regel) K. Larsen], Medicago truncatula Gaertn. (barrel medic), and soybean [Glycine max (L.) Merr.]. A total of 96, 98, and 304 homologs of flowering genes were identified in L. corniculatus var. japonicus, M. truncatula, and G. max, respectively. Most of these genes were categorized into seven different flowering pathways, including photoperiod, vernalization, gibberellins, autonomous pathways, floral pathway integrators (FPIs), and floral meristem identity. Many key genes, including the FPI genes FT, SOC1, and LFY, are conserved in the legumes while CO, FRI, FLC, and FD were not. Eighteen genes were conserved as single copy genes in all three legume species, including GI, VRN2, COP1, and TSF. The chromosomal distribution of paralog‐rich genes revealed differences in the major evolutionary processes affecting flowering genes in legumes, including whole genome duplication in soybean, tandem duplication in M. truncatula, and ectopic duplication in L. corniculatus var. japonicus. High divergence was observed among the members of large gene families, most containing transcription factors, indicating the accumulation of gene copies and gene divergence during evolutionary adaptations to environmental changes.

Human Monogenic Disease Genes Have Frequently Functionally Redundant Paralogs

Mendelian disorders are often caused by mutations in genes that are not lethal but induce functional distortions leading to diseases. Here we study the extent of gene duplicates that might compensate genes causing monogenic diseases. We provide evidence for pervasive functional redundancy of human monogenic disease genes (MDs) by duplicates by manifesting 1) genes involved in human genetic disorders are enriched in duplicates and 2) duplicated disease genes tend to have higher functional similarities with their closest paralogs in contrast to duplicated non-disease genes of similar age. We propose that functional compensation by duplication of genes masks the phenotypic effects of deleterious mutations and reduces the probability of purging the defective genes from the human population; this functional compensation could be further enhanced by higher purification selection between disease genes and their duplicates as well as their orthologous counterpart compared to non-disease genes. However, due to the intrinsic expression stochasticity among individuals, the deleterious mutations could still be present as genetic diseases in some subpopulations where the duplicate copies are expressed at low abundances. Consequently the defective genes are linked to genetic disorders while they continue propagating within the population. Our results provide insight into the molecular basis underlying the spreading of duplicated disease genes.

A conserved histone deacetylase with a role in the regulation of cytokinesis in Schizosaccharomyces pombe

BackgroundIn Schizosaccharomyces pombe the SET domain protein, Set3p - together with its interacting partners, Snt1p, and Hif2p - form a complex that aids in preventing cell division failure upon mild cytokinetic stress. Intriguingly, the human orthologs of these proteins (MLL5, NCOR2, and TBL1X) are also important for the faithful completion of cytokinesis in tissue culture cells. Since MLL5, NCOR2, and TBL1X form a complex with the histone deacetylase, HDAC3, we sought to determine if an orthologous counterpart played a regulatory role in fission yeast cytokinesis.ResultsIn this report we identify the hos2 gene as the fission yeast HDAC3 ortholog. We show that Hos2p physically interacts with Set3p, Snt1p, and Hif2p, and that hos2∆ mutants are indeed compromised in their ability to reliably complete cell division in the presence of mild cytokinetic stresses. Furthermore, we demonstrate that over-expression of hos2 causes severe morphological and cytokinetic defects. Lastly, through recombinase mediated cassette exchange, we show that expression of human HDAC3 complements the cytokinetic defects exhibited by hos2∆ cells.ConclusionsThese data support a model in which Hos2p functions as an essential component of the Set3p-Snt1p-Hif2p complex with respect to the regulation of cytokinesis. The ability of human HDAC3 to complement the cytokinesis defects associated with the deletion of the hos2 gene suggests that further analysis of this system could provide insight into the role of HDAC3 in both the regulation of cell division, as well as other biological processes influenced by HDAC3 deacetylation.

Using Drosophila as a model system to study cold tolerance

The simple genetics yet high homology of Drosophila genes to their orthologous counterparts in higher organisms and the availability of genetic perturbation toolkits make Drosophila species a powerful system for cold tolerance tests. Particular enzymes including adenosine monophosphate phosphatase have previously been shown to underlie cold tolerance in ice worms by regulating the body energy levels. The mechanism is assumed to be linked to rates of mitochondrial oxidative metabolism; this, in turn, causes the shutdown of molecular thermostats and allows for cold tolerance. To evaluate for cold tolerance in Drosophila, we developed a mobility test of third‐instar larvae under different temperatures. Our results indicate that significant differences in mobility across species are present between certain specified temperature intervals. Remarkably, adult flies survived more than three times longer in lower temperature than that in room temperature. Our findings of tolerance in lower temperatures provide tools to continue studying the effects of lower temperatures on the wild type and genetically perturbed flies, contributing ultimately to the research on extending the tight 24‐hour period shelf life of donated human organs. This research is supported by Dean's Undergraduate Research Fund and Travel Fund and by NIH‐NIGMS R15 GM093685‐01 awarded to DS and NY.

Atypical epigenetic mark in an atypical location: cytosine methylation at asymmetric (CNN) sites within the body of a non-repetitive tomato gene

BackgroundEukaryotic DNA methylation is one of the most studied epigenetic processes, as it results in a direct and heritable covalent modification triggered by external stimuli. In contrast to mammals, plant DNA methylation, which is stimulated by external cues exemplified by various abiotic types of stress, is often found not only at CG sites but also at CNG (N denoting A, C or T) and CNN (asymmetric) sites. A genome-wide analysis of DNA methylation in Arabidopsis has shown that CNN methylation is preferentially concentrated in transposon genes and non-coding repetitive elements. We are particularly interested in investigating the epigenetics of plant species with larger and more complex genomes than Arabidopsis, particularly with regards to the associated alterations elicited by abiotic stress.ResultsWe describe the existence of CNN-methylated epialleles that span Asr1, a non-transposon, protein-coding gene from tomato plants that lacks an orthologous counterpart in Arabidopsis. In addition, to test the hypothesis of a link between epigenetics modifications and the adaptation of crop plants to abiotic stress, we exhaustively explored the cytosine methylation status in leaf Asr1 DNA, a model gene in our system, resulting from water-deficit stress conditions imposed on tomato plants. We found that drought conditions brought about removal of methyl marks at approximately 75 of the 110 asymmetric (CNN) sites analysed, concomitantly with a decrease of the repressive H3K27me3 epigenetic mark and a large induction of expression at the RNA level. When pinpointing those sites, we observed that demethylation occurred mostly in the intronic region.ConclusionsThese results demonstrate a novel genomic distribution of CNN methylation, namely in the transcribed region of a protein-coding, non-repetitive gene, and the changes in those epigenetic marks that are caused by water stress. These findings may represent a general mechanism for the acquisition of new epialleles in somatic cells, which are pivotal for regulating gene expression in plants.

The Cellular Factors Vps18 and Mon2 Are Required for Efficient Production of Infectious HIV-1 Particles

Like all viruses, HIV-1 requires cellular host factors for replication. The mechanisms for production of progeny virions involving these host factors, however, are not fully understood. To better understand these mechanisms, we used a yeast (Saccharomyces cerevisiae) genetic screen to identify mutant strains in which HIV-1 Gag targeting to the plasma membrane was aberrant. Of the 917 mutants identified, we selected 14 mutants whose missing genes had single orthologous counterparts in human and tested them for Gag-induced viruslike particle (VLP) release in yeast cells. We found that the Vps18 and Mon2 proteins were important for HIV-1 Gag-induced VLP release in yeast. In eukaryote cells, these host proteins are highly conserved and function in protein trafficking. Depletion of hVps18 or hMon2 reduced the efficient production of infectious HIV-1 virions in human cells. Our data suggest that these cellular factors play an important role in the efficient production of infectious HIV-1 virion particles.

Proposed new nomenclature for Bos taurus cytochromes P450 involved in xenobiotic drug metabolism

The cytochrome P450 (CYP) superfamily of drug metabolizing enzymes (DMEs) plays a central role in the oxidative metabolism of xenobiotics to which living organisms are exposed. In Bos taurus (cattle), a definitive nomenclature for CYP proteins is still lacking, and to unambiguously settle cattle nomenclature a phylogenetic analysis of proteins belonging to CYP 1-4 families was performed. Sequences collected from GenBank and Dr Nelson's P450 homepage databases were analyzed according to the maximum likelihood method. Phylogenetic outputs showed that CYPs sharing the same name and collected from different species did not form, in several instances, monophyletic groups. Some cattle CYPs did not group with their supposed human orthologous counterparts, thus requiring a new nomenclature. Name changes mostly mirrored the orthologous counterparts established for other species, and new names were created when no clear orthologous sequences were identified. The new nomenclature will allow a more appropriate investigation of biochemical and molecular mechanisms involved in the expression and regulation of these DMEs.

Families of H/ACA ncRNA molecules in Trypanosomatids

H/ACA molecules are small nucleolar RNAs (snoRNAs) that guide the conversion of a uridine into a pseudouridine. This modification is crucial for ribosomal RNA (rRNA) function. In addition, H/ACA RNA also function in ribosomal RNA processing. Unlike the double hairpin structure of H/ACA molecules in other organisms, H/ACA molecules in Trypanosomes have a single hairpin structure. Here we describe the repertoire of H/ACA molecules of the 46 published of Trypanosoma brucei, as well as identify the orthologous counterparts in other Trypanosomatids enlarging the H/ACA collection in this family to over 300.

Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases

BackgroundAlternative splicing (AS) is a primary mechanism of functional regulation in the human genome, with 60% to 80% of human genes being alternatively spliced. As part of the bovine genome annotation team, we have analysed 4567 bovine AS genes, compared to 16715 human and 16491 mouse AS genes, along with Gene Ontology (GO) analysis. We also analysed the two most important events, cassette exons and intron retention in 94 human disease genes and mapped them to the bovine orthologous genes. Of the 94 human inherited disease genes, a protein domain analysis was carried out for the transcript sequences of 12 human genes that have orthologous genes and have been characterised in cow.ResultsOf the 21,755 bovine genes, 4,567 genes (21%) are alternatively spliced, compared to 16,715 (68%) in human and 16,491 (57%) in mouse. Gene-level analysis of the orthologous set suggested that bovine genes show fewer AS events compared to human and mouse genes. A detailed examination of cassette exons across human and cow for 94 human disease genes, suggested that a majority of cassette exons in human were present and constitutive in bovine as opposed to intron retention which exhibited 50% of the exons as present and 50% as absent in cow. We observed that AS plays a major role in disease implications in human through manipulations of essential/functional protein domains. It was also evident that majority of these 12 genes had conservation of all essential domains in their bovine orthologous counterpart, for these human diseases.ConclusionWhile alternative splicing has the potential to create many mRNA isoforms from a single gene, in cow the majority of genes generate two to three isoforms, compared to six in human and four in mouse. Our analyses demonstrated that a smaller number of bovine genes show greater transcript diversity. GO definitions for bovine AS genes provided 38% more functional information than currently available in the sequence database. Our protein domain analysis helped us verify the suitability of using bovine as a model for human diseases and also recognize the contribution of AS towards the disease phenotypes.