FoxO gene family evolution in vertebrates

<p>Abstract</p> <p>Background</p> <p>Forkhead box, class O (FoxO) belongs to the large family of forkhead transcription factors that are characterized by a conserved forkhead box DNA-binding domain. To date, the FoxO group has four mammalian members: FoxO1, FoxO3a, FoxO4 and FoxO6, which are orthologs of DAF16, an insulin-responsive transcription factor involved in regulating longevity of worms and flies. The degree of homology between these four members is high, especially in the forkhead domain, which contains the DNA-binding interface. Yet, mouse FoxO knockouts have revealed that each FoxO gene has its unique role in the physiological process. Whether the functional divergences are primarily due to adaptive selection pressure or relaxed selective constraint remains an open question. As such, this study aims to address the evolutionary mode of FoxO, which may lead to the functional divergence.</p> <p>Results</p> <p>Sequence similarity searches have performed in genome and scaffold data to identify homologues of FoxO in vertebrates. Phylogenetic analysis was used to characterize the family evolutionary history by identifying two duplications early in vertebrate evolution. To determine the mode of evolution in vertebrates, we performed a rigorous statistical analysis with FoxO gene sequences, including relative rate ratio tests, branch-specific <it>d</it>_<it>N</it>/<it>d</it>_{<it>S </it>}ratio tests, site-specific <it>d</it>_<it>N</it>/<it>d</it>_{<it>S </it>}ratio tests, branch-site <it>d</it>_<it>N</it>/<it>d</it>_{<it>S </it>}ratio tests and clade level amino acid conservation/variation patterns analysis. Our results suggest that FoxO is constrained by strong purifying selection except four sites in FoxO6, which have undergone positive Darwinian selection. The functional divergence in this family is best explained by either relaxed purifying selection or positive selection.</p> <p>Conclusion</p> <p>We present a phylogeny describing the evolutionary history of the FoxO gene family and show that the genes have evolved through duplications followed by purifying selection except for four sites in FoxO6 fixed by positive selection lie mostly within the non-conserved optimal PKB motif in the C-terminal part. Relaxed selection may play important roles in the process of functional differentiation evolved through gene duplications as well.</p

A Comparative Study of Mouse Hepatic and Intestinal Gene Expression Profiles under PPARα Knockout by Gene Set Enrichment Analysis

Gene expression profiling of PPARα has been used in several studies, but fewer studies went further to identify the tissue-specific pathways or genes involved in PPARα activation in genome-wide. Here, we employed and applied gene set enrichment analysis to two microarray datasets both PPARα related respectively in mouse liver and intestine. We suggested that the regulatory mechanism of PPARα activation by WY14643 in mouse small intestine is more complicated than in liver due to more involved pathways. Several pathways were cancer-related such as pancreatic cancer and small cell lung cancer, which indicated that PPARα may have an important role in prevention of cancer development. 12 PPARα dependent pathways and 4 PPARα independent pathways were identified highly common in both liver and intestine of mice. Most of them were metabolism related, such as fatty acid metabolism, tryptophan metabolism, pyruvate metabolism with regard to PPARα regulation but gluconeogenesis and propanoate metabolism independent of PPARα regulation. Keratan sulfate biosynthesis, the pathway of regulation of actin cytoskeleton, the pathways associated with prostate cancer and small cell lung cancer were not identified as hepatic PPARα independent but as WY14643 dependent ones in intestinal study. We also provided some novel hepatic tissue-specific marker genes

A comparative genome analysis of gene expression reveals different regulatory mechanisms between mouse and human embryo pre-implantation development

<p>Abstract</p> <p>Background</p> <p>Pre-implantation development is a crucial step in successful implantation and pregnancy in mammals. It has been studied in depth, but mostly in laboratory animal models. Less is known about the regulatory mechanism involved in the pre-implantation development in humans and about the comparative aspects.</p> <p>Methods</p> <p>Here, we employed the microarray datasets from the public database library of GEO and applied comparative analysis of genome wide temporal gene expression data based on statistical analysis and functional annotation for both mouse and human, demonstrating the discordance between the regulatory mechanisms of both mouse and human pre-implantation development.</p> <p>Results</p> <p>There were differences between mouse and human pre-implantation development both in the global gene expression pattern and in the expression changes of individual genes at each stage, including different major transient waves of transcription profiles and some stage-specific genes and significantly related pathways. There also appeared to be different functional changes from one stage to another between mouse and human.</p> <p>Conclusions</p> <p>The analysis presented here lead to interesting and complementary conclusions that the regulatory mechanism of human pre-implantation development is not completely the same as the mouse. Not as the fact that 1-cell to 2-cell stage is important for mouse pre-implantation development, the 4-cell stage and 8-cell stage are both essential for human. Unlike in mouse, of which most of pathways found were related to energy, RNA and protein metabolism, the identified pathways in human were mostly disease-related and associated with human pre-implantation embryonic development. All of these suggest that a further comparative analysis should be required for applying the result of mouse expression data to human research or therapy, particularly in pre-implantation developments. Our study provides several potential targets of genes and pathways for studying the regulatory mechanism of human pre-implantation development using mouse model.</p

ReCGiP, a database of reproduction candidate genes in pigs based on bibliomics

<p>Abstract</p> <p>Background</p> <p>Reproduction in pigs is one of the most economically important traits. To improve the reproductive performances, numerous studies have focused on the identification of candidate genes. However, it is hard for one to read all literatures thoroughly to get information. So we have developed a database providing candidate genes for reproductive researches in pig by mining and processing existing biological literatures in human and pigs, named as ReCGiP.</p> <p>Description</p> <p>Based on text-mining and comparative genomics, ReCGiP presents diverse information of reproduction-relevant genes in human and pig. The genes were sorted by the degree of relevance with the reproduction topics and were visualized in a gene's co-occurrence network where two genes were connected if they were co-cited in a PubMed abstract. The 'hub' genes which had more 'neighbors' were thought to be have more important functions and could be identified by the user in their web browser. In addition, ReCGiP provided integrated GO annotation, OMIM and biological pathway information collected from the Internet. Both pig and human gene information can be found in the database, which is now available.</p> <p>Conclusions</p> <p>ReCGiP is a unique database providing information on reproduction related genes for pig. It can be used in the area of the molecular genetics, the genetic linkage map, and the breeding of the pig and other livestock. Moreover, it can be used as a reference for human reproduction research.</p

Pig jejunal single-cell RNA landscapes revealing breed-specific immunology differentiation at various domestication stages

BackgroundDomestication of wild boars into local and intensive pig breeds has driven adaptive genomic changes, resulting in significant phenotypic differences in intestinal immune function. The intestine relies on diverse immune cells, but their evolutionary changes during domestication remain poorly understood at single-cell resolution.MethodsWe performed single-cell RNA sequencing (scRNA-seq) and marker gene analysis on jejunal tissues from wild boars, a Chinese local breed (Jinhua), and an intensive breed (Duroc). Then, we developed an immune cell evaluation system that includes immune scoring, gene identification, and cell communication analysis. Additionally, we mapped domestication-related clustering relationships, highlighting changes in gene expression and immune function.ResultsWe generated a single-cell atlas of jejunal tissues, analyzing 26,246 cells and identifying 11 distinct cell lineages, including epithelial and plasma cells, and discovered shared and unique patterns in intestinal nutrition and immunity across breeds. Immune cell evaluation analysis confirmed the conservation and heterogeneity of immune cells, manifested by highly conserved functions of immune cell subgroups, but wild boars possess stronger immune capabilities than domesticated breeds. We also discovered four patterns of domestication-related breed-specific genes related to metabolism, immune surveillance, and cytotoxic functions. Lastly, we identified a unique population of plasma cells with distinctive antibody production in Jinhua pig population.ConclusionsOur findings provide valuable single-cell insights into the cellular heterogeneity and immune function evolution in the jejunum during pig at various domestication stages. The single-cell atlas also serves as a resource for comparative studies and supports breeding programs aimed at enhancing immune traits in pigs

Twinning-assisted dynamic adjustment of grain boundary mobility

Grain boundary (GB) plasticity dominates the mechanical behaviours of nanocrystalline materials. Under mechanical loading, GB configuration and its local deformation geometry change dynamically with the deformation; the dynamic variation of GB deformability, however, remains largely elusive, especially regarding its relation with the frequently-observed GB-associated deformation twins in nanocrystalline materials. Attention here is focused on the GB dynamics in metallic nanocrystals, by means of well-designed in situ nanomechanical testing integrated with molecular dynamics simulations. GBs with low mobility are found to dynamically adjust their configurations and local deformation geometries via crystallographic twinning, which instantly changes the GB dynamics and enhances the GB mobility. This selfadjust twin-assisted GB dynamics is found common in a wide range of face-centred cubic nanocrystalline metals under different deformation conditions. These findings enrich our understanding of GB-mediated plasticity, especially the dynamic behaviour of GBs, and bear practical implication for developing high performance nanocrystalline materials through interface engineering

Genome-Wide and Trait-Specific Markers: A Perspective in Designing Conservation Programs

Nowadays, breed conservation has entered the genomics era and it is imperative to develop novel theory to design the breeding schemes of the conservation populations by using the genomic information. The genome-wide markers have been regarded as a useful strategy to maintain genetic diversity. However, using the genome-wide SNPs to optimize diversity might not be optimal for some specific loci associated with specific-traits. Using the sequencing data of the conserved population of the Saba pig breed, we demonstrated that the conservation program designed by using the genome-wide SNPs might result in the loss of the genetic diversity of the reproduction trait. We suggested an idea of using phylogenetic tree to select valuable individuals for conservation program based on the genome-wide and trait-specific makers. The selection rule was to make the selected samples to be widely distributed as much as possible in both the genome-wide and trait-specific phylogenetic trees