نوع مقاله : مقاله پژوهشی
نویسنده
گروه علوم دامی، دانشکده کشاورزی، دانشگاه یاسوج
چکیده
کلیدواژهها
موضوعات
عنوان مقاله [English]
نویسنده [English]
Introduction: The BRCA1 gene is a pivotal candidate in current research endeavors, specifically drawing significant attention in studies related to bovine mammary tumors and human breast cancer. This gene is recognized for its fundamental biological role, as it encodes a protein that primarily functions as a tumor suppressor. Understanding the intricate evolutionary trajectory and the degrees of conservation or divergence of the BRCA1 gene across various species is of paramount importance. Such an understanding can provide profoundly crucial insights into its underlying functional mechanisms and can offer invaluable comparative perspectives directly relevant to the development and progression of diseases in both human populations and livestock. Considering the substantial and impactful economic consequences that mammary tumors exert on agricultural productivity within cattle farming, alongside the pervasive and persistent challenge posed by breast cancer in human health, a detailed phylogenetic analysis of the BRCA1 gene across a broad and representative spectrum of species becomes an imperative scientific undertaking. This research endeavor specifically aimed to meticulously reconstruct the evolutionary history of the BRCA1 gene across a wide array of selected species. By successfully achieving this, it sought to contribute significantly to a deeper and more comprehensive understanding of its functional preservation across evolutionary time. Moreover, it is intended to explore its potential practical applications, which notably include informing more effective breeding strategies designed to foster disease-resistant livestock and guiding the development of novel diagnostic approaches pertinent to improving human health.
Materials and methods: In this computational study, the coding sequence (CDS) region of the BRCA1 gene was precisely extracted from the genomes of 32 mammalian species from the NCBI database. The extracted sequences were then aligned using the BLAST algorithm and MEGA software. To reconstruct the evolutionary relationships, five phylogenetic methods were employed: DNAPARS, Pars, PhyML, Dnaml, and Proml. This comprehensive approach allowed for a multifaceted analysis of the gene's evolutionary history. The current version of Dnaml is faster than its previous iterations. This algorithm accounts for unequal predicted frequencies of the four DNA bases and allows for different predicted frequencies of transitions and transversions, along with various methods for incorporating different rates of interaction at distinct DNA sites. Key assumptions of this algorithm include the independent evolution of each DNA site and different lineages. Proml, optimized for protein data, offers robust statistical inference.
Results and discussion: The application of various selected phylogenetic algorithms consistently revealed that all methods clustered closely related species, such as Bos taurus and Ovis aries, into similar phylogenetic groups. This consistent grouping strongly confirms the conserved functional role of BRCA1 in DNA repair and immune regulation. However, significant differences in phylogenetic tree topology were observed. Maximum likelihood methods (PhyML/Dnaml) grouped humans (Homo sapiens) with primates, showing bootstrap values of 65-75%. In contrast, maximum parsimony methods (DNAPARS/Pars) revealed weaker associations for rodents, with bootstrap values of 50-60%. The Proml algorithm, based on Bayesian inference, also showed uncertainty in estimating branch lengths. These differences highlight the sensitivity of the methods to the heterogeneous evolutionary rate of BRCA1 and underscore the necessity of using combined mRNA and protein data to reduce methodological biases. The results showed that most mammals are grouped into closely related clusters; however, even within a single phylogeny, maximum likelihood did not always yield consistent topologies, hinting at complex evolutionary dynamics not fully captured by single gene analyses.
Conclusions: The findings of this study not only illuminate the intricate evolutionary history of BRCA1 but also possess practical applications in breeding disease-resistant livestock and in human breast cancer research. Future research should investigate the role of horizontal gene transfer and its influence on BRCA1 evolution. This study ultimately provides a framework for the evolutionary analysis of disease-resistance genes. Given the crucial role of the BRCA1 gene in mammary tumors and breast cancer, the results of this study can provide a better evolutionary perspective across different species and be utilized in diagnostic assays for both humans and livestock. The study consistently showed that in most procedures and algorithms, bovine and ovine species form a very close evolutionary cluster. Therefore, the evolutionary results for one species can be applied to another. The BRCA1 gene, essential for maintaining genomic stability through its role in DNA repair and cell cycle regulation, exhibits a high degree of evolutionary conservation, particularly in the N-terminal RING domain and C-terminal BRCT domains. This was demonstrated in this study, indicating that these vital regions are conserved among various vertebrate species, underscoring their functional importance.
کلیدواژهها [English]
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