BMC Genomics最新文献

Effective metabolization of exogenous compounds in humans is a key for health and drug efficacy albeit a complex process determined by one's genetic background. The enzyme, N-Acetyltransferase-2 (NAT2), which metabolizes different xenobiotic compounds (including folate) and various therapeutic drugs, is encoded by the NAT2 gene. Based on acetylation capacity, an individual is either a fast or slow acetylator. Although the apportionment of NAT2 gene and its acetylator types are widely documented in human populations, the evolutionary genetic affinities and functional background of NAT2 variations with closely-related taxa are not well understood. Herein, we have analyzed 60 NAT2 gene coding sequences (873 bp) representing 59 different taxa belonging to mammalian and avian taxa and two most prevalent human NAT2 alleles ((NAT2*4 and NAT2*6A) to document the phylogenetics relationship among taxa; to characterize DNA methylation patterns in this gene and to evaluate species specific binding efficiency to folate using molecular docking approach. Phylogenetic analysis showed 3 broad clades representing where humans and other primates were found to be closely related. The CpG analysis revealed a one conserved region of same length (total 200 bp) across taxa as well as variable short regions of differing lengths (ranging from minimum 50 to maximum 100 bp length sequences) in some taxa. Molecular docking showed variable binding affinities of NAT2 protein models with human slow acetylator allele (NAT2*6A) showing highest binding affinity to folate, indicative of adaptive response to folate bioavailability. Through our analysis we highlight the evolutionary conservation and functional divergence in NAT2 gene across Mammals and Aves likely to be driven by ecological and dietary factors. Our findings provide new insights into evolutionary adaptations to processing folate across various taxa, which may be significant in studies focusing on evolutionary genetics of drug metabolism.

Background: The Rhododendron genus (Rhododendron L.), recognized as the most extensive woody plant genus in the Northern Hemisphere, captivates with its strikingly beautiful corollas and variety of flower colors. In addition, the Rhododendron genus exhibits a complex evolutionary history and substantial species diversification. To comprehensively understand the genomic complexity and flower color diversity within this genus, comparative genomics has emerged as a promising approach, enabling analysis at a super-species level.

Results: Here, we collected whole-genome data from seven rhododendrons of different subgenera to investigate the patterns of interspecific genomic and sequence divergence, as well as evolutionary dynamics of gene family related to flower color. We discovered that approximately 50% of Rhododendron genomes are composed of transposable elements (TEs), with over half of them being long terminal repeat retrotransposons (LTR-RTs). TEs significantly associate with genomic differentiation and structural variances within the genus. Additionally, the duplication and loss of genes associated with flower color and their corresponding expression over time are potentially driven by TEs.

Conclusion: Our comparative genomic analysis accentuates the critical role of TEs in genome divergence within the Rhododendron genus, highlighting their potential role as a key factor governing speciation and interspecific variability within the genus.

Background: Hanwoo cattle, a native Korean breed, display diverse coat colors, with White Hanwoo being extremely rare. Understanding the genetic basis of white coat color is essential for preserving genetic diversity and uncovering pigmentation mechanisms. This study aims to explore genetic differences between White and Brown Hanwoo and identify coat color-associated variants through genome-wide association study.

Results: Population structure analysis revealed clear genetic difference between the Brown Hanwoo (B×B) and White Hanwoo (W×W) groups. The W×W_White population exhibited the highest number of runs of homozygosity (ROH, n = 423) and the highest identity-by-descent (IBD) value (0.3547), suggesting reduced genetic diversity and potential inbreeding due to artificial selection. In contrast, the B×B_Brown group showed lower ROH (n = 78) and IBD (0.2956), indicating greater genetic variability. Genome-wide association study identified 3,482 SNPs significantly related to coat color. Notably, five missense variants were discovered in TYR, FAT3, ENSBTAG00000051637, and SPTY2D1, including a G-to-C substitution in exon 2 of the TYR gene. This mutation caused a glycine-to-arginine amino acid change, and structural modeling indicated a potential alteration in TYR protein conformation and hydrogen bonding, suggesting its involvement in melanin biosynthesis and coat color expression.

Conclusion: This study highlights significant genomic differences between White and Brown Hanwoo populations, including reduced genetic diversity in White Hanwoo due to potential inbreeding. In addition, it confirms the TYR gene as a critical determinant of coat color through the identification of a functionally relevant missense variant. These findings provide valuable insights for Hanwoo breeding and conservation strategies and lay the foundation for further functional studies on pigmentation-related genes.

Background: The genus Polycelis is characterized by the arrangement of multiple eye spots along the anterior dorsal margin of the head. These freshwater planarians are predominantly distributed in high-altitude ecosystems of temperate and subarctic zones across the Northern Hemisphere. Despite their significance as ecological bioindicators and models for regeneration, Polycelis remains controversial in taxonomy and phylogeny due to a critical lack of molecular data. Mitochondrial genomes (mitogenomes) have emerged as powerful tools for resolving deep phylogenetic relationships and species boundaries in morphologically conserved taxa. In this study, we present the first comparative mitogenomic analyses of four Polycelis species and phylogenetic reconstructions within Tricladida.

Results: Through next-generation sequencing, we successfully assembled four complete mitogenomes of Polycelis species. Each circular mitogenome contains 12 protein-coding genes (PCGs), 22 tRNA genes (tRNAs), 2 rRNA genes (rRNAs), and a non-coding region. Comparative genomic analyses revealed conservation in both gene arrangement and nucleotide compositions across the four species. The tandem repeat sequences and stem-loop structures were identified in their non-coding regions. Evolutionary analyses integrating nucleotide diversity (Pi), genetic distance, and Ka/Ks ratios across 12 PCGs demonstrated significant evolutionary heterogeneity: cox1 showed relatively low evolutionary rate, while nad6 displayed the highest sequence variability. Phylogenomic reconstruction using Bayesian inference (BI) and maximum likelihood (ML) methods based on 30 triclad mitogenomes, consistently resolved Polycelis as a monophyletic clade within Planariidae. Four Polycelis species exhibited synapomorphic gene rearrangements.

Conclusions: This study firstly elucidates Polycelis mitogenome architecture, evolutionary dynamics, providing critical insights into the genomic basis of mitochondrial evolution, the utility of mitogenomic data for molecular taxonomy, and the phylogenetic position of Polycelis within Tricladida. Additionally, this research offers valuable references for conservation and utilization of Polycelis genetic resources.

We used the Tibetan pig, a miniature swine breed, as a human heart model. By investigating the alterations in higher-order chromatin structure and transcriptional regulation spanning from the fetal stage to sexual maturity and early senescence, we aimed to elucidate their functions in physiological development and the aging process. To assess the Tibetan pig's suitability as a biomedical model and a potential organ donor for humans, we conducted cross-species comparisons of transcriptomes and chromatin structures between human and porcine hearts.Our study uncovered several previously unreported phenomena regarding structural changes in the three-dimensional genome across multiple scales. Changes in intensity of B-B interactions and correlation between sequence features and A/B compartment switches revealed that heterochromatin gradually stacked and relaxed during development and senescence. A finer examination of TADs and loops/PEIs showed that, compared to fetal and aged pigs, young adults boast higher correlation of gene expression and TAD connectivity, more space between dynamic boundaries and their targeted genes, and stronger 'loop skew' towards A compartments, indicating that young adults tend to have finer control of chromatin structure dynamics than fetal and aged pigs.Cross-species analyses of human-specific gene expression and chromatin structure changes compared to pigs indicated stronger cardiac contractility in humans, providing insights into evolution and physiological incompatibility of pig-to-human heart xenotransplantation. In particular, we found that human-specific loops showed motif enrichment of TFs TEAD1, TBX20 and ZEB2, whose target genes were mainly over-represented in cardiac contraction and fatty acid metabolism. In addition, we also observed human-specific elevated gene expression for TRPM1 and STIM, which reside in proximity to human-specific TAD boundaries and are known to play critical roles in calcium and potassium transmembrane transport.

Leaf morphology plays a crucial role in photosynthetic efficiency, environmental adaptation, and stress tolerance. Most Rosa species produce odd-pinnate compound leaves, whereas Rosa persica is the only species with simple leaves. In the wild, a naturally occurring deep-lobed leaf variant resembling a near-compound leaf was identified, providing a unique model for studying leaf development in woody plants. In this study, we aimed to characterize the NAC transcription factor family in R. persica and to investigate their roles in leaf margin morphogenesis. The NAC gene family was comprehensively analyzed using various bioinformatic approaches, including physicochemical property characterization, collinearity analysis and phylogenetic analyses, etc. Furthermore, WGCNA and expression profiling allowed the identification of five RpNAC genes, whose functions were subsequently investigated through subcellular localization, transcriptional activation assays, and heterologous overexpression in Arabidopsis thaliana. Candidate RpNAC proteins were nuclear-localized and exhibited transcriptional activation. Overexpression of RpNAP1 and RpNAC090.2 in Arabidopsis led to wavy leaf margins, increased leaf width, and enhanced chlorophyll content, indicating their important roles in leaf morphology and potential involvement in plant photosynthesis. These findings provide novel insights into the mechanism controlling leaf margin development in Rosa species and may facilitate targeted breeding of ornamental and stress-resilient traits.