历时10个月，代谢分工宇宙的第六篇作品终于被PNAS接收发表了！
这篇工作阐述了一个出人意料的发现：在模式分工群落的实验进化中，功能缺陷的分工种群通过水平基因转移，从合作同伴处获得了缺失的基因，反向演化成了功能完整的“超级菌株”。虽然大量宏基因组学的研究已经暗示了微生物间水平基因转移的广泛性，但本研究的发现提供了首个实验证据，表明在进化尺度上，水平基因转移可以介导群落中微生物相互作用关系的改变，即合作的崩溃和独立自治的出现。
关于文章的详细解读，请移步文章解读帖：靠队友不如靠自己？北大吴晓磊、聂勇组PNAS揭示分工向全能逆向演化机制 (qq.com)。本文主要讲述论文投稿PNAS过程的辛酸史：首轮被拒稿，申诉成功获得修改机会，后又经过3轮修改终于接收！虽然辛酸，但我们始终相信我们扎实和独具特色的研究工作，在一番努力终于成功发光了！这其中的心路历程，以及与编辑审稿人沟通的经验，想必会有同行朋友会感兴趣，于是单独写一个帖子来与大家分享。
-2023年10月：文章投稿并收到送审通知
-2023年12月初：收到第一轮审稿意见，拒稿
PNAS的完整决定信只会发给通讯作者，其他作者只会收到一个通知，里面没有审稿意见。看到邮件里的“rejection”决定时，内心当然是伤心的，不过还是心存侥幸，万一是“rejection but encouraging resubmission”呢？于是迫不及待跑到系统里去看了下完整决定信，以下是读整个决定信的心路历程。
1. 第一段是编辑部的模板意见，读完后内心拔凉拔凉的。
拒稿信第一段节选：“...These reviews, which appear below, were considered by the editor, who determined that the issues raised by the reviewers were of sufficient concern to merit rejection of the manuscript. Our goal at PNAS, to publish novel, transformational research rapidly, prevents us from undertaking multiple rounds of revision and re-review after receiving negative reviews. Accordingly, resubmission of the article will not be permitted.”
很显然，没有resubmission的可能性，就是彻彻底底的拒稿！
2. 第二段是handling Editor的具体意见，读完后内心有了很多疑惑。
前半段：“Both Reviewers appreciated the work described in this manuscript. The work connects the evolution of division of labor, evolution in fluctuating environments, and evolution through horizontal gene transfer. Extensive previous work has been done in all of these areas, but not combined in this way. There is also a nice integration of experiments and models.”
夸得这么狠，看起来不太像会给拒稿的样子啊！
后半段：“However, reviewers raised significant concerns about statements that are not justified by data and that would require extensive additional experiments. While this is strong work that will contribute to the field there was concern that the quality was ultimately not sufficient to warrant publication in PNAS. ”
好了，拒稿原因来了！看来是审稿人提出了要补比较复杂的实验，在短时间无法完成，所以决定拒稿。往下看审稿人都说了啥。
3. 然后仔细阅读了总共两位审稿人的意见，读完后觉得，太冤了！！！
审稿人1意见总结段：“The manuscript, although lengthy, provides a detailed description of methods and evolutionary concepts used during the work. Overall, a nicely-written and solid work, however, I am missing one crucial experiment... it might be easily demonstrated with such simple experiment. ”
虽然不完美，但至少Overall nicely-written and solid了，算是positive的审稿意见了。好像也没有extensive additional experiments要补，而只是一个simple but crucial experiment。
审稿人2意见总结段：“We would like to first start by thanking the authors for this very interesting paper, with a pleasingly counter-intuitive idea. Overall, we are convinced that there is solid support for their main hypotheses by both the experiments and the model. As far as we can tell, the idea is novel, and we estimate that it brings enough to the field to recommend the manuscript for publication. And while we do not have any major concerns with the manuscript, we would like to see some questions addressed to improve the readability and transparency of the manuscript. ”
看完第一句的内心戏：“不用谢，感谢您的喜欢！”整段看完，夸得有点狠，都不太好意思了（不过学到了新表达，以后审稿也多夸夸好的工作）。审稿人2也没有强制要求补充新的实验。虽然审稿意见中确实有一些实验要补（有很多还不是强制要补的，虽然我们最后都补了），但不像是extensive additional experiments！收到了两个positive 的审稿意见，却被拒稿，比窦娥还冤！既然如此，咱可不能就这么算了，得尝试着申诉！
-2023年12月底：发起申诉，给编辑怼回去
虽然要申诉，也得按程序来，咱也不能胡搅蛮缠。于是去查了PNAS关于被拒稿后申诉（Appeal）的说明（https://www.pnas.org/author-center/editorial-and-journal-policies#resubmissions-and-appeals）：
“Resubmissions to PNAS may be allowed upon request. Appeals must be made in writing and sent to pnas@nas.edu. PNAS may consider author appeals of decisions on rejected papers; however, appeals on the basis of novelty or general interest are unlikely to be granted. Due to the high volume of submissions that PNAS receives, a quick decision on appeals cannot be guaranteed. If an appeal is rejected, further appeals of the decision will not be considered and the paper may not be resubmitted. Repeated appeals or resubmissions of a rejected manuscript without invitation by the Editorial Board will not be considered and may result in the authors being banned from submitting to PNAS.”
关键信息包括：（1）首先需要写一封申诉信发到pnas@nas.edu；（2）申诉一般不能质疑编辑或审稿人对于创新性和general interest的判断；（3）只有申诉被编辑部考虑和接受以后，才能获得提交修改稿的机会（实际操作是，在线投稿系统会重新开放），强行重投可能会被放入黑名单！
所以，先准备一封申诉信吧，申诉信“应该尽可能详细地说明为什么编辑应重新考虑最初的拒稿决定”（providing as much specific detail as possible about why the original decision should be reconsidered，这句来自ISME J的投稿说明：https://academic.oup.com/ismej/pages/general-instructions）。以下是我们的申诉信：
Subject: Sincere Request for Reconsideration (Paper ###)
Manuscript titled 'The evolution of autonomy from two cooperative specialists in a fluctuating environment' (Paper ###)
Dear Editors,
I hope this message finds you well. On behalf of all the co-authors, I would like to express our sincere gratitude for the valuable feedback provided on our manuscript. We highly appreciate the efficient peer review process and the valuable comments from both reviewers.
Upon careful consideration of the reviewers' comments, we were somewhat surprised by the decision of the Editorial Board to decline our manuscript. Both reviewers, particularly Reviewer 2, provided largely positive evaluations, expressing support for the publication of our work.
(1) Reviewer 2 concluded that ‘Overall, we are convinced that there is solid support for their main hypotheses by both the experiments and the model. As far as we can tell, the idea is novel, and we estimate that it brings enough to the field to recommend the manuscript for publication.’ they said they ‘do not have any major concerns with the manuscript’, and just need us to address some questions.
(2) Reviewer 1 also offered an overall positive evaluation, ‘The manuscript, although lengthy, provides a detailed description of methods and evolutionary concepts used during the work. Overall, a nicely-written and solid work, however, I am missing one crucial experiment.’ This experiment is to test the fitness of the ancestor Autonomist in the presence of Degrader and Detoxifier (Experiment (1)) and they presented that ‘this might be easily demonstrated with such simple experiment,’ which we fully agree. In the specific suggestions, Reviewer 1 suggested three not-complicated experiments: Experiment (2) - Fitness assays between the ancestral Degrader and different evolved derivatives; Experiment (3) - An experimental evolution when only Degrader is started with; Experiment (4) - Fitness assays among the later evolved variants of Degrader.
We understand the importance of Experiment (1) and recognize its significance in further strengthening our conclusions. While direct relative fitness measurements are lacking, a recent study in PNAS (Ram et al., 2019: https://doi.org/10.1073/pnas.1902217116) proposed that growth curve data can accurately predict relative fitness. Therefore, we think our growth curve data in Figure 1A can partially support that the ancestral Autonomist has a higher fitness compared to the consortium. Nevertheless, we agree that direct fitness assays are also important but we believe that these simple fitness assays (Experiments (1), (2), and (4)) can be conducted within a short timeframe. While we acknowledge that Experiment (3) might be perceived as time-consuming, most of the required data are already available because we already finished several subsequent projects based on this work, including a systemically experimental evolution of only Degrader. In summary, we think that Reviewer 1 chose ‘No’ in the ‘Suitable Quality?’ and ‘Conclusions Justified?’ questions (which are the only two ‘No’s in all evaluations) because they need us to add these simple and manageable experiments to defend our conclusions and therefore meet the high standards of PNAS.
Overall, we fully agree with the comments from both reviewers and believe that the proposed revisions are fully manageable within an acceptable timeline. We are committed to fully addressing all concerns raised and revising the manuscript accordingly to meet the high bar of PNAS.
Therefore, with utmost respect, we are writing to you with trepidation to ask whether you can offer us an opportunity to revise the manuscript and resubmit it to PNAS for further consideration. We are eager to receive your guidance on the path forward and appreciate your time and consideration.
Thank you once again for your effort to advance scientific rigor and for your contributions to the peer review process of our manuscript! We are looking forward to your feedback and appreciate your time and consideration!
Sincerely yours,
XXX
总结一下几个要点：
（1）有礼貌，多用“appreciate”、“ Thank you”和“agree”这些词。诚恳地感谢编辑和审稿人的付出，并同意编辑和审稿人的大部分意见，有信心在短时间内完成针对性的修改。
（2）大力强调审稿人的意见很积极（暗指：这么positive，不应该拒稿）。
（3）针对编辑的拒稿原因进行详细回复。比如这里拒稿原因是需要补大量实验，那回复就应尽可能说明没有很多实验要补，具体包括：有些实验是很简单的，不花时间；有些实验的结果已经有了；有些结果还没有，但现有结果可以部分支持结论，有信心在短期内获得结果。
（4）如果部分审稿人意见比较negative，那会比较棘手，需要argue为什么审稿人给出的评价不客观、有失误，这就要依靠更高超的论述手法来说服编辑。当然，我们这次没有遇到这样的情况。
-2024年1月中：收到编辑部的回复，申诉信收到，耐心等待申诉结果。
-2024年2月初：申诉成功，系统重新开启，可提交修改稿。
收到申诉成功邮件时，还是很兴奋的。
“Thank you for your comments regarding the decision to decline your paper for publication in PNAS. We apologize for the delay with rendering a decision on your appeal request. The editor has decided to undertake a further evaluation of your work. Please keep in mind that there is no guarantee the original decision will be overturned.
You must submit your revised manuscript and point-by-point response within 60 days.”
虽然邮件里说得很保守（no guarantee the original decision will be overturned），但至少是有了新的机会。除此之外，3天后又收到了一封补充邮件，看起来像编辑重新阅读了文章，给了一个新意见。
“The authors provide interesting data demonstrating that fluctuating environments can contribute to horizontal gene transfer in mutualistic systems. They use mathematical models to demonstrate that fluctuating environments can contribute through both altering frequency and density of interdependent bacteria in a large parameter space. There is significant literature examining i) when division of labor is selected for and against, ii) how environmental fluctuation impacts coexistence, and iii) how frequency and density impact horizontal gene transfer. That being said less has been shown about when horizontal gene transfer will lead to the erosion of mutualism.”
看起来都是积极评价了，可说是推翻了之前的编辑意见，也算是增强了我们对文章最终能命中的信心。除了这个总结意见外，编辑还另外给了几条重要的修改意见，需要我们在回复审稿人意见的同时，进一步修改（暗示之前拒稿也是有理有据的）。
-2024年4月初：修改稿RA和回复审稿意见提交。
-2024年6月初：第二轮修改意见返回。
幸运地是，编辑没有找新的审稿人，只是将文章返回了原有的两个审稿人。
审稿人1：“Thank you for addressing all comments, even presenting experiments for those comments that might have been solved with rewriting the text. I have no additional remarks. Congratulations on this very neat work!”
直接通过了！不过看来实验补太多了，审稿人本意可能不需要补这么多实验。
审稿人2：“This is a second round of review for the manuscript "The evolution of autonomy from two cooperative specialists in fluctuating environments" by Chen and co-authors. We can see no major issues remaining and find the modifications to the manuscript to be satisfactory.”
也是满意我们的回复了！但审稿人2补充提了1个问题和一些语法问题，问题不大。最后又补充了一条评论：
“Finally, going forward, we encourage the authors to be more concise in their responses to reviewers. 50 pages of responses is arguably quite excessive, even considering the large amount of extra work done by the authors.”
好吧，回复意见写太长了。因为我们的习惯是，把修改的正文语句贴到对应的回复意见下面，所以会显得回复意见特别长。取决于不同审稿人的喜好，有些审稿人喜欢我们这种风格，这样不用再去翻看原文；有些不喜欢我们这种风格，因为回复意见太长，给人第一感受是头大。只能说，各有优劣，看运气吧！当然，在回复审稿人爸爸的这类意见时，当然是认怂：
“We sincerely apologize for the unclarity and potential redundancy of our responses... We sincerely apologize for any inconvenience caused and will improve our response manner in our future submissions.”
不过总结两个审稿人的意见来看，离成功不远了，我们都预测下一轮文章应该会被接收了！
-2024年6月中：修改稿RR和回复审稿意见提交。
-2024年6月底：第三轮修改意见返回，没错，还有第三轮！！
没想到吧！两个审稿人都同意接收以后，编辑又给了十几条的语法修改意见：
“Editor Comments: I have one last round of suggestions to improve clarity of the writing.”
这些意见总体很好，帮助我们进一步提高了文章的质量，这里分享和讨论其中的几条意见（仅代表个人观点）！
意见1：“I would strongly encourage the authors to include more of the methods in the main text rather than having the majority in the supplementary information. I would ask the authors not to lengthen the paper to do this but instead to attempt to reduce text in other sections of the paper. ”
对这条意见非常支持！我们一直非常赞同详细地描述研究方法，以使同行可以重复研究结果，这也是严谨科学研究的基本要求。然而，PNAS对于文章长度有着严格限制（6-12页，包括图、图例和参考文献等所有内容），因此增加方法内容，意味着需要删减正文内容，同时篇幅限制也无法让方法描述得非常充分，依然要大量借助附件材料。这种模式代表了大多数老派杂志的排版要求，由于正文篇幅受限，需要在附件中补充大量的方法甚至结果，PNAS也鼓励这么做，这使得读者既能选择短时间读完正文，了解文章的核心内容；也可以选择进一步研读详细的方法。
另一种则是以Cell Press和eLife为代表的新刊模式。这类杂志以在线发表为主，没有太多的版面限制。以Cell Press旗下的杂志为例，其方法部分（STAR★Methods）独立于正文，没有任何字数限制，并通过固定格式要求作者尽可能详细地描述方法，以提高研究的可重复性，且Cell Press不允许附件材料中有方法描述，这样所有方法都连贯性地展示在一起，方便读者一并查阅。文章正式发表后，作者还可以选择把详细方法整理后发表在Cell Press旗下的STAR Protocols上。个人比较欣赏这种强制措施，这迫使作者提高研究的透明性（transparent），当然真正推行起来可能是有难度的。
意见2：“I appreciate that the authors added caveatsto these statements in later paragraphs. However, for clarity, I would still either recommend dropping the statement or incorporating the caveats with the initial statement... As noted above I would recommend removing the caveat from this paragraph.”
这条意见是让删除文中对文章不足（limitations或caveats）的描述。如果有读者阅读过我们代谢分工宇宙的前五部作品，或许都知道我们都会在最后一段描述本文研究的不足，以警示研究者在引用结果时需要注意的限制条件，以及为之后的研究提供一些方向。我觉得这是现代科学研究发展的趋势，“no research is ever perfect”（这是来自之前一篇文章一位审稿人的话），不过编辑可能是基于文章篇幅的考虑要求精简。修改中，我们把一些不足整理到了附件中，但还有许多本来要申明的“坑”就删掉了，只能向读者们说一声抱歉！
意见3：“Figures 3 and 4: The colors for degrader, detoxifier and autonomist remain difficult to distinguish at least from my printer. This is particularly true for figure 4. ”
这里先放一下原本的Figure 4截选
再放一张修改后的Figure 4：
确实更加distinguishable了，代价是，所有图的配色和风格全部都修改了，以使配色描述统一，花了两周时间！现在的科研人，不仅要好好搞科研，还得有艺术细胞，计算机作图更是基本功，挺难的！关于图片配色的选择，应该有好多公众号教程，有艺术细胞的同学也可以从世界名画当中去截取配色。一句忠告是，一开始就把配色选好，省得到最后了还得痛苦地修改配色！
-2024年7月中：修改稿RRR和回复意见提交。
-2024年8月初：终于终于，文章正式接受！
暂时接收：“We are pleased to inform you that the PNAS Editorial Board has given provisional approval of your article for publication.”
正式接收：“Congratulations on the formal acceptance of your article, "The evolution of autonomy from two cooperative specialists in fluctuating environments" in PNAS. Your manuscript and any supplemental files have now been transferred to our production vendor. ”
相信这是科研人最珍爱的两句话了！10个月的折腾，终于终于尘埃落定！文章接收当天，正在瑞士少女峰徒步，傍晚看到了少女峰的日照金山。看来好运气总是同时到来，也希望把好运气传递给各位辛苦的科研人！
-结语
是金子总会发光！科学研究中，坚持不懈当然是非常重要的！但除此之外，还想强调另外两点：
（1）研究本身得是金子！所以，研究本身几大要素不可或缺：创新性、数据严谨性和general interest。这次我们敢申诉也是因为对文章质量有底气（毕竟两个审稿意见也都是positive的）。在明知研究有显著漏洞的情况下，即使申诉也不会有好结果。现在科研圈发好文章的压力很大，但好的科研需要沉下心来思考、一步步踏实推进，而不是靠碰运气！
（2）申诉得按程序来！就像PNAS的规定一样，强行重投有可能被拉入黑名单！所以，收到拒稿信时还是要冷静分析，有无申诉可能？期刊申诉流程是啥样的？与编辑诚恳沟通寻求机会。回复意见时，该怂还得怂（大佬课题组的同学除外）！在科研工作中，与别人沟通和交流是很重要的（所以E人可能更适合现代科研？哈哈哈）。
最后，来个俗一点的结尾：祝大家发文章都顺利，没有拒稿，别用上我们的经验！
作者简介：
王淼啸，瑞士苏黎世联邦理工学院（ETH Zürich）博士后研究员，工作于Martin Ackermann教授和Olga Schubert研究员所领导的课题组。主要研究方向包括：微生物间相互作用机制及其生态学意义，微生物群落组装及演化机制，合成微生物组的理性设计与构建原理。在PNAS, Cell Systems, Cell Reports、ISME Journal等期刊上发表学术论文20篇，其中第一或通讯作者署名9篇。担任mLife杂志海外兼职编辑；iMeta青年编委；ISME Journal、eLife、ISME Communications等杂志审稿人。热爱户外徒步，是瑞士最大的华人户外徒步团体Crazy Hikers Zürich的领队之一。小红书徒步博主@一天成天旅行的科研🐶。
