Tuesday, September 29, 2020

Gene Loss Association Study (GLAS) in budding yeast gets published in PeerJ

A central goal in evolutionary biology is the identification of changes in the genome that result in  changes at the level of the phenotype. Associating gene loss events with a specific phenotype has seen increasing interest with the availability of high quality genome assemblies for large numbers of species. A detailed discussion of the approach and examples of associations that have been successfully established is provided in Shinde et al. 2019. Graphical summary of the idea of Gene Loss Association Studies or GLAS is provided in below figure.


Figure 1 from Shinde et al. 2019

Two years ago, while screening the budding yeast genomes to identify associations between gene loss and kinetochore phenotypes, it became apparent that four genes from the inner kinetochore were missing in Naumovozyma species. The Kobayashi et al. 2015 paper had studied centromeres in both Naumovozyma species with genome assemblies using ChIP-seq and established the uncoventional point centromeres. Hence, this association between gene loss and transition to evolutionary neo-centromeres (ENC's) seemed an important observation to better understand the processes involved in generating ENC's. While the manuscript was under preparation, an influential study (Kasinathan et al 2018) about defining features of centromeres was published from the Henikoff lab. This study was important as they compared sequence characteristics of Naumovozyma centromeres in addition to several other species. Continuing on the work from Henikoff lab we compared the dyad density of the old and new centromeres in both Naumovozyma species. 

Being a bird coloration enthusiast i studied plumage coloration in crows during my PhD. A prominent discovery in the field of bird morphs around this time was the identification of a large chromosomal inversion in Ruff's that associates with a morph polymorphism (see Kupper et al 2016). One breakpoint of this inversion is known to disrupt the essential CENP-N gene. As a result of this lethality, individuals homozygous for the inversion allele don't exist. The existence of this balanced polymorphism has been the focus of subsequent research. One of the four genes that were found to be lost in Naumovozyma was CHL4, an ortholog of CENP-N. This is an interesting example of a gene which can be essential in certain species while becoming dispensable in a different group of species. 

Given the recent interest in neo-centromere formation and its evolutionary emergence and role in karyotype evolution, the time seems ripe for understanding the sequence of genetic events involved in such transitions. Role of centromere repositioning in reproductive isolation has also received attention. My manuscript describing the GLAS in budding yeast was submitted to PeerJ for Peer review sometime after the nationwide lockdown took hold of India (18th of June). Manuscript was assessed by 3 reviewers, each of whom gave constructive and detailed comments. Quality of the manuscript definitely improved based on the feedback from these anonymous reviewers and the editor. Since, PeerJ provides an option to publish the reviewer comments along with the manuscript, these comments can be seen online. Revision is due in approximately 40 days with some flexibility as no fixed deadline is provided. This is a very useful feature as the time taken to revise a manuscript can vary widely from one manuscript to another. Overall turnaround time for the reviews seemed reasonable and matched with how detailed the reviewer comments were. First set of reviewer comments were received (on 21st July) approximately 1 month after submission. It took me another one month (19th August) to revise the manuscript as other manuscripts had shorter timelines. PeerJ staff checked the manuscript for various issues to ensure it is properly formatted prior to the second round of review. All this was completed by 26th August. The article was finally accepted on 11th September after a second round of review. PeerJ surprisingly does not have an interactive review system and might be for the better. The total time from submission to acceptance was 86 days (~3 months). Proofing of the article was a very smooth experience that involved annotating the pdf proof and uploading it back again. Shortly after the proof was submitted, the article was scheduled for publication on Sep 29th, 2020. This follows in the tradition of PeerJ publishing articles on every Tuesday and Thursday. The publication is now available on the PeerJ website with the title "Loss of inner kinetochore genes is associated with the transition to an unconventional point centromere in budding yeast"