Protein domains are found on genomes with notable statistical distributions, which bear a high degree of similarity. Previous work has shown how these distributions can be accounted for by simple models, where the main ingredients are probabilities of duplication, innovation, and loss of domains. However, no one so far has addressed the issue that these distributions follow definite trends depending on protein-coding genome size only. We present a stochastic duplication/innovation model, falling in the class of so-called Chinese Restaurant Processes, able to explain this feature of the data. Using only two universal parameters, related to a minimal number of domains and to the relative weight of innovation to duplication, the model reproduces two important aspects: (a) the populations of domain classes (the sets, related to homology classes, containing realizations of the same domain in different proteins) follow common power-laws whose cutoff is dictated by genome size, and (b) the number of domain families is universal and markedly sublinear in genome size. An important ingredient of the model is that the innovation probability decreases with genome size. We propose the possibility to interpret this as a global constraint given by the cost of expanding an increasingly complex interactome.
Motivation: Protein-to-genome alignment is critical to annotating genes in non-model organisms. While there are a few tools for this purpose, all of them were developed over ten years ago and did not incorporate the latest advances in alignment algorithms. They are inefficient and could not keep up with the rapid production of new genomes and quickly growing protein databases. Results: Here we describe miniprot, a new aligner for mapping protein sequences to a complete genome. Miniprot integrates recent techniques such as k-mer sketch and SIMD-based dynamic programming. It is tens of times fas…
Replication of SARS-CoV2 virions is an error-prone process which may eventually generate a percentage of impaired protein copies with complete lack of functionality. For instance, after RNA mis-replication, a very premature stop codon (UAG, UAA, UGA) coding for a prematurely truncated (nonsense-mutated) spike protein may occur. In the natural virus replication process via cell infection, the nonsense genomes are corrected by the proofreading enzymes of the virus, strongly penalized by natural selection and condemned to a very short life by the host cell's mRNA watching mechanisms. However, for…
Protein structure and sequence re-analysis of 2019-nCoV genome does not indicate snakes as its intermediate host or the unique similarity between its spike protein insertions and HIV-1
由于2019-nCoV冠状病毒感染正在迅速发展成为全球肺炎疫情，因此迫切需要对其传播和细胞机制进行仔细分析。在这份报告中，我们重新分析了Ji et al.（https：//doi.org/10.1002/jmv.25682）和Pradhan et al.（https：//doi.org/10.1101/2020.01.30.927871）最近两篇手稿中提出的计算方法和发现，得出的结论是蛇是2019-nCoV的中间宿主，2019-nCoV刺突蛋白插入与HIV-1具有独特的相似性。我们使用最先进的生物信息学方法和数据库在更大规模的数据集上重新实施分析的结果不支持这些手稿提出的结论。根据我们的分析和冠状病毒的现有数据，我们得出结论，2019-nCoV的中间宿主更有可能是哺乳动物和鸟类，而不是蛇，并且在刺突蛋白中观察到的“新插入”是从蝙蝠冠状病毒自然进化而来的。
Range-Limited Heaps' Law for Functional DNA Words in the Human Genome
Stony Brook University（石溪大学）；The Feinstein Institutes for Medical Research, Northwell Health（费因斯坦医学研究所，诺思韦尔健康）；Institute of Nanoscience and Nanotechnology National Center for Scientific Research, “Demokritos”（纳米科学与技术研究所，德谟克利特国家科学研究中心）
Bacterial genomes have been shown to be partitioned into several kilobases long chromosomal domains that are topologically independent from each other, meaning that change of DNA superhelicity in one domain does not propagate to neighbors. Both in vivo and in vitro experiments have been performed to question the nature of the topological barriers at play, leading to several predictions on possible molecular actors. Here, we address the question of topological barriers using polymer models of supercoiled DNA chains. More specifically, we determine under which conditions DNA-bridging proteins ma…
Increasing biological complexity is positively correlated with the relative genome-wide expansion of non-protein-coding DNA sequences
背景资料：在当前的基因组时代之前，有人认为生物体所使用的蛋白质编码基因的数量是衡量其复杂性的有效指标。然而，现在很清楚的是，主要的不一致性存在，生物复杂性和蛋白质编码基因的数量之间只有微弱的关系。例如，使用蛋白质编码基因数量作为评估生物复杂性的基础，将使尾索动物和昆虫的复杂性低于线虫，而人类的复杂性低于水稻。结果如下：我们分析了85个测序物种的非编码基因组DNA与总基因组DNA的比率（ncDNA/tgDNA），发现这个比率与生物学复杂性的增加密切相关。对于原核生物，ncDNA/tgDNA比率通常包含在0.05-0.24的带宽内，但在单细胞真核生物中上升到0.26-0.52，并且对于发育复杂的多细胞生物体上升到0.62-0.985。值得注意的是，原核生物物种的物种分布不均匀，接近平均值0.1177 ncDNA/tgDNA（p=1.58 x 10^-13），ncDNA/tgDNA与基因组大小呈非线性关系（r=0.15）。重要的是，ncDNA/tgDNA比率校正倍性，并且基本上不受重复序列的可变负荷的影响。结论：我们认为，所观察到的非编码DNA的增加和组成模式主要是增加的信息含量的函数。因此，内含子、基因间序列、重复元件和基因组DNA可能对复杂生物的进化和功能库比以前认识到的要重要得多。
Scientists have been trying to identify all of the genes in the human genome since the initial draft of the genome was published in 2001. Over the intervening years, much progress has been made in identifying protein-coding genes, and the estimated number has shrunk to fewer than 20,000, although the number of distinct protein-coding isoforms has expanded dramatically. The invention of high-throughput RNA sequencing and other technological breakthroughs have led to an explosion in the number of reported non-coding RNA genes, although most of them do not yet have any known function. A combinati…
Genome assembly is a fundamental problem in Bioinformatics, requiring to reconstruct a source genome from an assembly graph built from a set of reads (short strings sequenced from the genome). A notion of genome assembly solution is that of an arc-covering walk of the graph. Since assembly graphs admit many solutions, the goal is to find what is definitely present in all solutions, or what is safe. Most practical assemblers are based on heuristics having at their core unitigs, namely paths whose internal nodes have unit in-degree and out-degree, and which are clearly safe. The long-standing op…
As organisms are faced with intense rapidly changing selective pressures, new genetic material is required to facilitate adaptation. Among sources of genetic novelty, gene duplications and transposable elements (TEs) offer new genes or new regulatory patterns that can facilitate evolutionary change. With advances in genome sequencing it is possible to gain a broader view of how gene family proliferation and TE content evolve in non-model species when populations become threatened. Freshwater bivalves (Unionidae) currently face severe anthropogenic challenges. Over 70% of species in the United …
