Department of Zoology, The Government Sadiq College Women University, Bahawalpur, 63100, Punjab, Pakistan.
Department of Veterinary and Animal Sciences, University of Veterinary and Animal Sciences, Lahore, Punjab, Pakistan.
Mol Biotechnol. 2024 Nov;66(11):3336-3356. doi: 10.1007/s12033-023-00944-3. Epub 2023 Nov 1.
We systematically analyzed BMP gene family in H. sapiens to elucidate genetic structure, phylogenetic relationships, adaptive evolution and tissue-specific expression pattern. Total of 13 BMPs genes were identified in the H. sapiens genome. Bone morphogenetic proteins (BMPs) are composed of a variable number of exons ranging from 2 to 21. They exhibit a molecular weight ranging from 31,081.81 to 82,899.61 Da. These proteins possess hydrophilic characteristics, display thermostability, and exhibit a pH range from acidic to basic. We identified four segmental and two tandem duplication events in BMP gene family of H. sapiens. All of the vertebrate species that were studied show the presence of BMPs 1, 2, 3, 4, 5, 6, 7, 8A, and 15, however only Homo sapiens demonstrated the presence of BMP9 and BMP11. The pathway and process enrichment analysis of BMPs genes showed that these were considerably enriched in positive regulation of pathway-restricted SMAD protein phosphorylation (92%) and cartilage development (77%) biological processes. These genes exhibited positive selection signals that were shown to be conserved across vertebrate lineages. The results showed that BMP2/3/5/6/8a/15 proteins underwent adaptive selection at many amino acid locations and increased positive selection was detected in TGF-β propeptide and TGF-β super family domains which were involved in dorso-ventral patterning, limb bud development. More over the expression pattern of BMP genes revealed that BMP1 and BMP5; BMP4 and BMP6 exhibited substantially identical expression patterns in all tissues while BMP10, BMP15, and BMP3 showed tissue-specific expression.
我们系统地分析了人类中的 BMP 基因家族,以阐明其遗传结构、系统发育关系、适应性进化和组织特异性表达模式。在人类基因组中总共鉴定出 13 个 BMP 基因。骨形态发生蛋白(BMPs)由 2 到 21 个可变数目的外显子组成。它们的分子量范围从 31081.81 到 82899.61Da。这些蛋白质具有亲水性,表现出热稳定性,并且具有从酸性到碱性的 pH 范围。我们在人类的 BMP 基因家族中鉴定出了四个片段和两个串联重复事件。所有研究过的脊椎动物物种都显示出存在 BMPs1、2、3、4、5、6、7、8A 和 15,然而只有人类显示出存在 BMP9 和 BMP11。BMPs 基因的通路和过程富集分析表明,这些基因在通路受限的 SMAD 蛋白磷酸化(92%)和软骨发育(77%)的正向调控中显著富集。这些基因表现出正向选择信号,这些信号在脊椎动物谱系中是保守的。结果表明,BMP2/3/5/6/8a/15 蛋白在许多氨基酸位置经历了适应性选择,并且在 TGF-β前肽和 TGF-β超家族结构域中检测到了增加的正选择,这些结构域参与了背腹模式形成、肢体芽发育。此外,BMP 基因的表达模式表明,BMP1 和 BMP5;BMP4 和 BMP6 在所有组织中表现出基本相同的表达模式,而 BMP10、BMP15 和 BMP3 表现出组织特异性表达。