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91.
Whole-genome duplication (polyploidization) is among the most dramatic mutational processes in nature, so understanding how natural selection differs in polyploids relative to diploids is an important goal. Population genetics theory predicts that recessive deleterious mutations accumulate faster in allopolyploids than diploids due to the masking effect of redundant gene copies, but this prediction is hitherto unconfirmed. Here, we use the cotton genus (Gossypium), which contains seven allopolyploids derived from a single polyploidization event 1–2 Million years ago, to investigate deleterious mutation accumulation. We use two methods of identifying deleterious mutations at the nucleotide and amino acid level, along with whole-genome resequencing of 43 individuals spanning six allopolyploid species and their two diploid progenitors, to demonstrate that deleterious mutations accumulate faster in allopolyploids than in their diploid progenitors. We find that, unlike what would be expected under models of demographic changes alone, strongly deleterious mutations show the biggest difference between ploidy levels, and this effect diminishes for moderately and mildly deleterious mutations. We further show that the proportion of nonsynonymous mutations that are deleterious differs between the two coresident subgenomes in the allopolyploids, suggesting that homoeologous masking acts unequally between subgenomes. Our results provide a genome-wide perspective on classic notions of the significance of gene duplication that likely are broadly applicable to allopolyploids, with implications for our understanding of the evolutionary fate of deleterious mutations. Finally, we note that some measures of selection (e.g., dN/dS, πN/πS) may be biased when species of different ploidy levels are compared. 相似文献
92.
Rohit Suratekar Pritha Ghosh Michiel J M Niesen Gregory Donadio Praveen Anand Venky Soundararajan A J Venkatakrishnan 《Molecular systems biology》2022,18(2)
The highly contagious Delta variant of SARS‐CoV‐2 has become a prevalent strain globally and poses a public health challenge around the world. While there has been extensive focus on understanding the amino acid mutations in the Delta variant’s Spike protein, the mutational landscape of the rest of the SARS‐CoV‐2 proteome (25 proteins) remains poorly understood. To this end, we performed a systematic analysis of mutations in all the SARS‐CoV‐2 proteins from nearly 2 million SARS‐CoV‐2 genomes from 176 countries/territories. Six highly prevalent missense mutations in the viral life cycle‐associated Membrane (I82T), Nucleocapsid (R203M, D377Y), NS3 (S26L), and NS7a (V82A, T120I) proteins are almost exclusive to the Delta variant compared to other variants of concern (mean prevalence across genomes: Delta = 99.74%, Alpha = 0.06%, Beta = 0.09%, and Gamma = 0.22%). Furthermore, we find that the Delta variant harbors a more diverse repertoire of mutations across countries compared to the previously dominant Alpha variant. Overall, our study underscores the high diversity of the Delta variant between countries and identifies a list of amino acid mutations in the Delta variant’s proteome for probing the mechanistic basis of pathogenic features such as high viral loads, high transmissibility, and reduced susceptibility against neutralization by vaccines. 相似文献
93.
It has previously been shown that, conditional on its fixation, the time to fixation of a semi-dominant deleterious autosomal mutation in a randomly mating population is the same as that of an advantageous mutation. This result implies that deleterious mutations could generate selective sweep-like effects. Although their fixation probabilities greatly differ, the much larger input of deleterious relative to beneficial mutations suggests that this phenomenon could be important. We here examine how the fixation of mildly deleterious mutations affects levels and patterns of polymorphism at linked sites—both in the presence and absence of interference amongst deleterious mutations—and how this class of sites may contribute to divergence between-populations and species. We find that, while deleterious fixations are unlikely to represent a significant proportion of outliers in polymorphism-based genomic scans within populations, minor shifts in the frequencies of deleterious mutations can influence the proportions of private variants and the value of FST after a recent population split. As sites subject to deleterious mutations are necessarily found in functional genomic regions, interpretations in terms of recurrent positive selection may require reconsideration. 相似文献
94.
Paloma Acebo María Teresa Alda Manuel Espinosa Gloria del Solar 《FEMS microbiology letters》1996,140(1):85-91
Abstract Streptococcus pneumoniae genetic systems designed for isolation of plasmid mutants with copy-up phenotypes have been developed. The target plasmids have the pLS1 replicon, and two different strategies have been followed: (i) selection of clones exhibiting augmented resistance to antibiotics, or (ii) obligatory co-existence of incompatible plasmids. We have isolated 23 plasmid mutants exhibiting increased number of copies. All the mutations corresponded to four different alleles of the copG gene of plasmid pLS1. These strategies could be used with other plasmids. 相似文献
95.
96.
《Structure (London, England : 1993)》2020,28(2):244-251.e3
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97.
The hypothesis of the exclusively genetic origin of cancer (cancer is a disease of genes, a tumor without any damage to the genome does not exist) dominated in the oncology until recently. A considerable amount of data confirming this hypothesis was accumulated during the last quarter of the last century. It was demonstrated that the accumulation of damage of specific genes lies at the origin of a tumor and its following progression. The damage gives rise to structural changes in the respective proteins and, consequently, to inappropriate mitogenic stimulation of cells (activation of oncogenes) or to the inactivation of tumor suppressor genes that inhibit cell division, or to the combination of both (in most cases). According to an alternative (epigenetic) hypothesis that was extremely unpopular until recently, a tumor is caused not by a gene damage, but by an inappropriate function of genes (cancer is a disease of gene regulation and differentiation). However, recent studies led to the convergence of these hypotheses that initially seemed to be contradictory. It was established that both factors–genetic and epigenetic–lie at the origin of carcinogenesis. The relative contribution of each varies significantly in different human tumors. Suppressor genes and genes of repair are inactivated in tumors due to their damage or methylation of their promoters (in the latter case an epimutation, an epigenetic equivalent of a mutation, occurs, producing the same functional consequences). It is becoming evident that not only the mutagens, but various factors influencing cell metabolism, notably methylation, should be considered as carcinogens. 相似文献
98.
Computational studies on mutant protein stability: The correlation between surface thermal expansion and protein stability
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Thermal stability of mutant proteins has been investigated using temperature dependent molecular dynamics (MD) simulations in vacuo. The numerical modeling was aimed at mimicking protein expansion upon heating. After the conditions for an expanding protein accessible surface area were established for T4 lysozyme and barnase wild-type proteins, MD simulations were carried out under the same conditions using the crystal structures of several mutant proteins. The computed thermal expansion of the accessible surface area of mutant proteins was found to be strongly correlated with their experimentally measured stabilities. A similar, albeit weaker, correlation was observed for model mutant proteins. This opens the possibility of obtaining stability information directly from protein structure. 相似文献
99.
通道病理学是当今国际学术发展中一门新兴学科。本文将针对有关电压门控钠通道的变异所导致的机体疾患,如高血钾性周期性麻痹,先天性肌强直等骨骼肌疾患,LQT3,原发笥心室纤颤等心脏病及其所涉及的钠通道突变体,通道的突变位点和电生理性质等一些研究资料与进展作一概括介绍。 相似文献
100.
Cassava breeding: opportunities and challenges 总被引:4,自引:0,他引:4
Although cassava is a major food crop, its scientific breeding began only recently compared with other crops. Significant progress has been achieved, particularly in Asia where cassava is used mainly for industrial processes and no major biotic constraints affect its productivity. Cassava breeding faces several limitations that need to be addressed. The heterozygous nature of the crop and parental lines used to generate new segregating progenies makes it difficult to identify parents with good breeding values. Breeding so far has been mainly based on a mass phenotypic recurrent selection. There is very little knowledge on the inheritance of traits of agronomic relevance. Several approaches have been taken to overcome the constraints in the current methodologies for the genetic improvement of cassava. Evaluations at early stages of selection allow for estimates of general combining ability effect or breeding values of parental lines. Inbreeding by sequential self-pollination facilitates the identification of useful recessive traits, either already present in the Manihot gene pool or induced by mutagenesis. 相似文献