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实验评估新进化的小鼠基因 Pldi 的直接适应度效应。

Experimental Evaluation of a Direct Fitness Effect of the De Novo Evolved Mouse Gene Pldi.

机构信息

Department of Evolutionary Genetics, Max-Planck Institute for Evolutionary Biology, 24306 Plön, Germany.

Present address: Max Planck Institute for Biological Intelligence, 82152 Martinsried, Germany.

出版信息

Genome Biol Evol. 2024 May 2;16(5). doi: 10.1093/gbe/evae084.

DOI:10.1093/gbe/evae084
PMID:38742287
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11091481/
Abstract

De novo evolved genes emerge from random parts of noncoding sequences and have, therefore, no homologs from which a function could be inferred. While expression analysis and knockout experiments can provide insights into the function, they do not directly test whether the gene is beneficial for its carrier. Here, we have used a seminatural environment experiment to test the fitness of the previously identified de novo evolved mouse gene Pldi, which has been implicated to have a role in sperm differentiation. We used a knockout mouse strain for this gene and competed it against its parental wildtype strain for several generations of free reproduction. We found that the knockout (ko) allele frequency decreased consistently across three replicates of the experiment. Using an approximate Bayesian computation framework that simulated the data under a demographic scenario mimicking the experiment's demography, we could estimate a selection coefficient ranging between 0.21 and 0.61 for the wildtype allele compared to the ko allele in males, under various models. This implies a relatively strong selective advantage, which would fix the new gene in less than hundred generations after its emergence.

摘要

从头进化而来的基因出现在非编码序列的随机区域,因此没有可以推断其功能的同源物。虽然表达分析和敲除实验可以提供对功能的深入了解,但它们并不能直接测试该基因是否对其载体有益。在这里,我们使用半自然环境实验来测试先前鉴定的从头进化的小鼠基因 Pldi 的适应性,该基因被认为在精子分化中发挥作用。我们使用该基因的敲除(ko)小鼠品系,并在几代自由繁殖中与亲本野生型品系竞争。我们发现,在实验的三个重复中,ko 等位基因频率持续下降。使用近似贝叶斯计算框架,根据模拟实验人口统计学的人口统计学情景模拟数据,我们可以估计在雄性中,与 ko 等位基因相比,野生型等位基因的选择系数在 0.21 到 0.61 之间,在各种模型下。这意味着相对较强的选择优势,这将使新基因在其出现后的不到一百代中固定下来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/11091481/de7f99845617/evae084f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/11091481/36ec04a403a5/evae084f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/11091481/1caef454f401/evae084f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/11091481/de7f99845617/evae084f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/11091481/36ec04a403a5/evae084f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/11091481/1caef454f401/evae084f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97fe/11091481/de7f99845617/evae084f3.jpg

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The Effects of Sequence Length and Composition of Random Sequence Peptides on the Growth of Cells.随机序列肽的序列长度和组成对细胞生长的影响。
Genes (Basel). 2021 Nov 28;12(12):1913. doi: 10.3390/genes12121913.
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Depletion of high-mobility group box 2 causes seminiferous tubule atrophy via aberrant expression of androgen and estrogen receptors in mouse testis†.
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Biol Reprod. 2021 Dec 20;105(6):1510-1520. doi: 10.1093/biolre/ioab187.
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Dedicated transcriptomics combined with power analysis lead to functional understanding of genes with weak phenotypic changes in knockout lines.专注的转录组学结合强大的分析能力,使我们能够深入理解在基因敲除系中具有微弱表型变化的基因的功能。
PLoS Comput Biol. 2020 Nov 12;16(11):e1008354. doi: 10.1371/journal.pcbi.1008354. eCollection 2020 Nov.
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Inbred lab mice are not isogenic: genetic variation within inbred strains used to infer the mutation rate per nucleotide site.近交系实验鼠并非同基因:用于推断每个核苷酸位点突变率的近交系内的遗传变异。
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