{"title":"共同使用的基因更有可能在进化过程中通过突变机制融合在一起:对 \"使用-融合假说 \"的生物信息学检验》(Bioinformatic Test of the Used-Fused Hypothesis)。","authors":"Evgeni Bolotin, Daniel Melamed, Adi Livnat","doi":"10.1007/s11692-022-09579-9","DOIUrl":null,"url":null,"abstract":"<p><p>Cases of parallel or recurrent gene fusions in evolution as well as in genetic disease and cancer are difficult to explain, because unlike point mutations, they can require the repetition of a similar configuration of multiple breakpoints rather than the repetition of a single point mutation. The used-together-fused-together hypothesis holds that genes that are used together repeatedly and persistently in a specific context are more likely to undergo fusion mutation in the course of evolution for mechanistic reasons. This hypothesis offers to explain gene fusion in both evolution and disease under one umbrella. Using bioinformatic data, we tested this hypothesis against alternatives, including that all gene pairs can fuse by random mutation, but among pairs thus fused, those that had interacted previously are more likely to be favored by selection. Results show that across multiple measures of gene interaction, human genes whose orthologs are fused in one or more species are more likely to interact with each other than random pairs of genes of the same genomic distance between pair members; that an overlap exists between genes that fused in the course of evolution in non-human species and genes that undergo fusion in human cancers; and that across six primate species studied, fusions predominate over fissions and exhibit substantial evolutionary parallelism. Together, these results support the used-together-fused-together hypothesis over its alternatives. Multiple implications are discussed, including the relevance of mutational mechanisms to the evolution of genome organization, to the distribution of fitness effects of mutation, to evolutionary parallelism and more.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s11692-022-09579-9.</p>","PeriodicalId":50471,"journal":{"name":"Evolutionary Biology","volume":"50 1","pages":"30-55"},"PeriodicalIF":1.9000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925542/pdf/","citationCount":"0","resultStr":"{\"title\":\"Genes that are Used Together are More Likely to be Fused Together in Evolution by Mutational Mechanisms: A Bioinformatic Test of the Used-Fused Hypothesis.\",\"authors\":\"Evgeni Bolotin, Daniel Melamed, Adi Livnat\",\"doi\":\"10.1007/s11692-022-09579-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cases of parallel or recurrent gene fusions in evolution as well as in genetic disease and cancer are difficult to explain, because unlike point mutations, they can require the repetition of a similar configuration of multiple breakpoints rather than the repetition of a single point mutation. The used-together-fused-together hypothesis holds that genes that are used together repeatedly and persistently in a specific context are more likely to undergo fusion mutation in the course of evolution for mechanistic reasons. This hypothesis offers to explain gene fusion in both evolution and disease under one umbrella. Using bioinformatic data, we tested this hypothesis against alternatives, including that all gene pairs can fuse by random mutation, but among pairs thus fused, those that had interacted previously are more likely to be favored by selection. Results show that across multiple measures of gene interaction, human genes whose orthologs are fused in one or more species are more likely to interact with each other than random pairs of genes of the same genomic distance between pair members; that an overlap exists between genes that fused in the course of evolution in non-human species and genes that undergo fusion in human cancers; and that across six primate species studied, fusions predominate over fissions and exhibit substantial evolutionary parallelism. Together, these results support the used-together-fused-together hypothesis over its alternatives. Multiple implications are discussed, including the relevance of mutational mechanisms to the evolution of genome organization, to the distribution of fitness effects of mutation, to evolutionary parallelism and more.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s11692-022-09579-9.</p>\",\"PeriodicalId\":50471,\"journal\":{\"name\":\"Evolutionary Biology\",\"volume\":\"50 1\",\"pages\":\"30-55\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925542/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Evolutionary Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s11692-022-09579-9\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/11/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"EVOLUTIONARY BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Evolutionary Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s11692-022-09579-9","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/11/30 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"EVOLUTIONARY BIOLOGY","Score":null,"Total":0}
Genes that are Used Together are More Likely to be Fused Together in Evolution by Mutational Mechanisms: A Bioinformatic Test of the Used-Fused Hypothesis.
Cases of parallel or recurrent gene fusions in evolution as well as in genetic disease and cancer are difficult to explain, because unlike point mutations, they can require the repetition of a similar configuration of multiple breakpoints rather than the repetition of a single point mutation. The used-together-fused-together hypothesis holds that genes that are used together repeatedly and persistently in a specific context are more likely to undergo fusion mutation in the course of evolution for mechanistic reasons. This hypothesis offers to explain gene fusion in both evolution and disease under one umbrella. Using bioinformatic data, we tested this hypothesis against alternatives, including that all gene pairs can fuse by random mutation, but among pairs thus fused, those that had interacted previously are more likely to be favored by selection. Results show that across multiple measures of gene interaction, human genes whose orthologs are fused in one or more species are more likely to interact with each other than random pairs of genes of the same genomic distance between pair members; that an overlap exists between genes that fused in the course of evolution in non-human species and genes that undergo fusion in human cancers; and that across six primate species studied, fusions predominate over fissions and exhibit substantial evolutionary parallelism. Together, these results support the used-together-fused-together hypothesis over its alternatives. Multiple implications are discussed, including the relevance of mutational mechanisms to the evolution of genome organization, to the distribution of fitness effects of mutation, to evolutionary parallelism and more.
Supplementary information: The online version contains supplementary material available at 10.1007/s11692-022-09579-9.
期刊介绍:
The aim, scope, and format of Evolutionary Biology will be based on the following principles:
Evolutionary Biology will publish original articles and reviews that address issues and subjects of core concern in evolutionary biology. All papers must make original contributions to our understanding of the evolutionary process.
The journal will remain true to the original intent of the original series to provide a place for broad syntheses in evolutionary biology. Articles will contribute to this goal by defining the direction of current and future research and by building conceptual links between disciplines. In articles presenting an empirical analysis, the results of these analyses must be integrated within a broader evolutionary framework.
Authors are encouraged to submit papers presenting novel conceptual frameworks or major challenges to accepted ideas.
While brevity is encouraged, there is no formal restriction on length for major articles.
The journal aims to keep the time between original submission and appearance online to within four months and will encourage authors to revise rapidly once a paper has been submitted and deemed acceptable.