• Evolutionary Tinkering Enriches the Hierarchical and Interlaced Structures in Amino Acid Sequences

    分类: 信息科学与系统科学 >> 信息科学与系统科学基础学科 分类: 生物学 >> 生物进化论 分类: 生物学 >> 生物数学 分类: 物理学 >> 交叉学科物理及相关领域的科学与技术 分类: 生物学 >> 遗传学 提交时间: 2023-10-15

    摘要: Background: In bioinformatics, tools like multiple sequence alignment and entropy methods probe sequence information and evolutionary relationships between species. Although powerful, they might miss crucial hierarchical relationships formed by the reuse of repetitive subsequences like duplicons and transposable elements. Such relationships are governed by “evolutionary tinkering'', as described by Fran c{c}ois Jacob. The newly developed Ladderpath theory provides a quantitative framework to describe these hierarchical relationships.

    Results: Based on this theory, we introduce two indicators: order-rate $ eta$, characterizing sequence pattern repetitions and regularities, and ladderpath-complexity $ kappa$, characterizing hierarchical richness within sequences, considering sequence length. Statistical analyses on real amino acid sequences showed: (1) Among the typical species analyzed, humans possess relatively more sequences with large $ kappa$ values. (2) Proteins with a significant proportion of intrinsically disordered regions exhibit increased $ eta$ values. (3) There are almost no super long sequences with low $ eta$. We hypothesize that this arises from varied duplication and mutation frequencies across different evolutionary stages, which in turn suggests a zigzag pattern for the evolution of protein complexity. This is supported by our simulations and examples from protein families such as Ubiquitin and NBPF.

    Conclusions: Our method emphasizes “how objects are generated'', capturing the essence of evolutionary tinkering and reuse. The findings hint at a connection between sequence orderliness and structural uncertainty, and suggest that different species or those in varied environments might adopt distinct protein elongation strategies. These insights highlight our method's value for further in-depth evolutionary biology applications.

  • 使用 Mimics 进行 3D 重建时不同复原精度对头骨测量数值的影响

    分类: 生物学 >> 遗传学 提交时间: 2023-06-01

    摘要: 在古人类研究中,骨骼,尤其是头骨性状的测量是获得标本特征信息的主要手段。随着技术的发展,CT技术及三维复原技术为骨骼测量带来了巨大的便利。其中Mimics软件作为常用的三维重建软件之一,在复原过程中为使用者提供了低、中、高、最佳这四种精度的选择。我们希望获知在不同复原精度得到的模型上进行测量得到的结果存在何种程度的差异,以便在未来研究过程中选择最合适的标准。在本研究中,我们选择了顶骨矢状弦、颅周、头盖面积、乳突小房表面积、颅容量、乳突小房体积这六项性状的测量数据作为检测指标,计算同一批现代人标本在Mimics中采用不同精度复原得到的模型间测量数值的差异,根据Mimics的复原模型简化规则,我们选择未精简的最佳精度模型作为标准进行非参数检验、配对t检验及计算测量差异占比。结果表明,这六项的不同简化精度模型测量数据与最佳精度模型测量数据的非参数检验及配对t检验均具有显著差异。顶骨矢状弦、颅周、头盖面积、颅容量的测量差异占比基本均小于3%,而乳突小房表面积的低精度测量差异占比可达到50%以上,乳突小房体积低精度测量差异占比可达120%以上。除去简化过程造成的模型表面膨胀外,乳突小房的多气房结构造成不同精度之间存在的绝对差异比上一整体体量小区域而形成的巨大相对差异提示我们,在三维模型的测量中,对于头骨内部腔窦这样小体量表面粗糙的部分的复原精度选择及数据比较需要格外谨慎。

  • Revisiting the genetic diversity and population structure of the endangered Green Sea Turtle (Chelonia mydas) breeding populations in the Xisha (Paracel) Islands, South China Sea

    分类: 生物学 >> 遗传学 提交时间: 2022-12-22

    摘要: The Green Sea Turtle (Chelonia mydas) is an umbrella species in the South China Sea, a Chinese national first-level protected wild animal, and the only sea turtle that nests in Chinese waters. The largest C. mydas nesting ground is distributed in the Xisha (Paracel) Islands, which plays a vital role in the survival of sea turtle populations in China. This study reveals the genetic diversity and population structure of the breeding population of C. mydas on the Xisha Islands using three mitochondrial markers. A total of 15 D-loop, 5 Cytochrome b (Cyt b), and 7 Cytochrome C Oxidase subunit I (COI) haplotypes were identified in the breeding population of C. mydas on the Xisha Islands. D-loop haplotypes are distributed in clades III, IV, and VIII of the C. mydas mitochondrial control region. Clade IV is first clade to be discovered in this C. mydas population, and five D-loop haplotypes were also newly identified. The haplotype and nucleotide diversity were calculated for each marker: D-loop (0.415 haplotype diversity, 0.00204 nucleotide diversity), Cyt b (0.140, 0.00038) and COI (0.308, 0.00083). The average genetic distance (p) of each molecular marker was less than 0.01. Neutral detection and nucleotide mismatch analysis suggested that the breeding population of C. mydas in the Xisha Islands did not experience a population expansion event in recent history. It is recommended that a sea turtle protection area be established in the Xisha Islands area to strengthen protection and effectively protect the uniqueness and sustainability of the breeding population of C. mydas in the South China Sea.绿海龟是中国南海的伞护种,国家一级保护野生动物,也是唯一在我国海域筑巢的海龟。西沙群岛分布有中国最大的绿海龟产卵场,对我国海龟种群的生存起着至关重要的作用。本研究利用3个线粒体基因标记揭示了西沙群岛绿海龟繁殖种群的遗传多样性和种群结构。在西沙群岛绿海龟繁殖种群共鉴定出15个D-loop单倍型、5个Cytb单倍型和7个COI单倍型;D-loop单倍型分布在进化支Ⅲ、Ⅳ和Ⅷ,其中进化支Ⅳ首次在西沙群岛绿海龟繁殖种群中发现,且最新发现了5个D-loop单倍型。计算每个标记的单倍型和核苷酸多样性: D-loop(单倍型多样性为0.415,核苷酸多样性为0.00204)、Cyt b(0.140, 0.00038)和COI(0.308, 0.00083)。各分子标记的平均遗传距离(p)均≦0.01。中性检测和核苷酸错配分析显示,西沙群岛绿海龟繁殖种群在近期历史上未经历种群扩张事件。建议在西沙群岛地区建立海龟保护区加强保护,以有效保护中国南海地区绿海龟繁殖种群的特殊性和可持续性。

  • Germline Polymorphisms and Length of Survival of Nasopharyngeal Carcinoma: An Exome-Wide Association Study in Multiple Cohorts

    分类: 医学、药学 >> 临床医学 分类: 生物学 >> 遗传学 提交时间: 2020-03-06

    摘要: Germline polymorphisms have been linked with differential survival outcomes in cancers but have not been well studied in nasopharyngeal carcinoma (NPC). Here, two-phase association study is conducted to discover germline polymorphisms that are associated with the prognosis of NPC. The discovery phase includes two consecutive hospital cohorts of patients with NPC from Southern China. Exome-wide genotypes at 246,173 single nucleotide polymorphisms (SNPs) are determined, followed by survival analysis for each SNP under Cox proportional hazards regression model. Candidate SNP is replicated in another two independent cohorts from Southern China and Singapore. Meta-analysis of all samples (n = 5,553) confirm that the presence of rs1131636-T, located in the 3′-UTR of RPA1, confers an inferior overall survival (HR = 1.33, 95% CI = 1.20-1.47, P = 6.31 × 10-8). Bioinformatics and biological assays show that rs1131636 has regulatory effects on upstream RPA1. Functional studies further demonstrate that RPA1 promoted the growth, invasion, migration, and radioresistance of NPC cells. Additionally, miR-1253 has been identified as a suppressor for RPA1 expression, likely through regulation of its binding affinity to rs1131636 locus. Collectively, these findings provide a promising biomarker aiding in stratifying patients with poor survival, as well as a potential drug target for NPC.

  • 利用全基因组数据解码新型肺炎冠状病毒的进化和传播

    分类: 生物学 >> 病毒学 分类: 生物学 >> 生物进化论 分类: 生物学 >> 遗传学 提交时间: 2020-02-21

    摘要: Background. The outbreak of COVID-19 started in mid-December 2019 in Wuhan, Central China. Up to February 18, 2020, SARS-CoV-2 has infected more than 70,000 people in China, and another 25 countries across five continents. In this study, we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFluTM database to decode the evolution and human-to-human transmissions of SARS-CoV-2 in the recent two months. Methods. Alignment of coding-regions was conducted haplotype analyses using DnaSP. Substitution sites were analyzed in codon. Evolutionary analysis of haplotypes used NETWORK. Population size changes were estimated using both DnaSP and Arlequin. Expansion date of population size was calculated based on the expansion parameter tau (τ) using the formula t=τ/2u. Findings. Eight coding-regions have 120 substitution sites, including 79 non-synonymous and 40 synonymous substitutions. Forty-two non-synonymous substitutions changed the biochemical property of amino acids. No evident combination was found. Fifty-eight haplotypes were classified as five groups, and 31 haplotypes were found in samples from both China and other countries, respectively. The rooted network suggested H13 and H35 to be ancestral haplotypes, and H1 (and its descendent haplotypes including all samples from the Hua Nan market) was derived H3 haplotype. Population size of SARS-CoV-2 were estimated to have a recent expansion on 6 January 2020, and an early expansion on 8 December 2019. Interpretation. Genomic variations of SARS-CoV-2 are still low in comparisons with published genomes of SARS-CoV and MERS-CoV. Phyloepidemiologic analyses indicated the SARS-CoV-2 source at the Hua Nan market should be imported from other places. The crowded market boosted SARS-CoV-2 rapid circulations in the market and spread it to the whole city in early December 2019. Furthermore, phyloepidemiologic approaches have recovered specific direction of human-to-human transmissions, and the import sources of international infectious cases.

  • PIK3CA and AKT2 mutations of gastric cancer in China

    分类: 生物学 >> 遗传学 提交时间: 2018-03-16

    摘要: Mutations in PI3K and/or AKT have been reported in a variety of cancers. This indicates that the two pathways interact to cause cancer. We have therefore investigated their roles in gastric cancer (GC) in China. In our study, exons 9, 18 and 20 of PIK3CA gene and exons 6~14 of AKT2 gene were screened in 10 GC cell lines and 100 advanced primary GC together with matched normal tissues. Denaturing high performance liquid chromatography (DHPLC) and DNA sequencing were used to analyze the mutations in the two genes. Two point mutations in the PIK3CA gene were identified in 4 of 10 GC cell lines and in 4 of 100 GC primary tumors. Two polymorphisms in AKT2 were detected in 19 of 100 GC primary tumors. One point mutation in AKT2 was detected in 1 of 10 GC cell lines and 3 of 100 GC primary tumors, and no hot spot variation was detected. Our results indicate that PIK3CA and AKT2 mutations are found in GC, although not a common event, therefore they might still play an important role in mediating kinase activities towards gastric carcinogenesis.