Sometimes, important factors for explaining biological processes fall through the cracks, and it is only through careful modeling that their importance eventually comes out to light. In this study, Barroso and Dutheil introduce a new method based on the sequentially Markovian coalescent (SMC, Marjoran and Wall 2006) for jointly estimating local recombination and coalescent rates along a genome. Unlike previous SMC-based methods, however, their method can also co-estimate local patterns of variation in mutation rates. 

This is a powerful improvement which allows them to tackle questions about the reasons for the extensive variation in nucleotide diversity across the chromosomes of a species - a problem that has plagued the minds of population geneticists for decades (Begun and Aquadro 1992, Andolfatto 2007, McVicker et al., 2009, Pouyet and Gilbert 2021). The authors find that variation in de novo mutation rates appears to be the most important factor in determining nucleotide diversity in Drosophila melanogaster. Though seemingly contradicting previous attempts at addressing this problem (Comeron 2014), they take care to investigate and explain why that might be the case.

Barroso and Dutheil have also taken care to carefully explain the details of their new approach and have carried a very thorough set of analyses comparing competing explanations for patterns of nucleotide variation via causal modeling. The reviewers raised several issues involving choices made by the authors in their analysis of variance partitioning, the proper evaluation of the role of linked selection and the recombination rate estimates emerging from their model. These issues have all been extensively addressed by the authors, and their conclusions seem to remain robust. The study illustrates why the mutation landscape should not be ignored as an important determinant of local variation in genetic diversity, and opens up questions about the generalizability of these results to other organisms.

REFERENCES

Andolfatto, P. (2007). Hitchhiking effects of recurrent beneficial amino acid substitutions in the Drosophila melanogaster genome. Genome research, 17(12), 1755-1762. https://doi.org/10.1101/gr.6691007

Barroso, G. V., & Dutheil, J. Y. (2021). The landscape of nucleotide diversity in Drosophila melanogaster is shaped by mutation rate variation. bioRxiv, 2021.09.16.460667, ver. 3 peer-reviewed and recommended by Peer Community in Evolutionary Biology. https://doi.org/10.1101/2021.09.16.460667

Begun, D. J., & Aquadro, C. F. (1992). Levels of naturally occurring DNA polymorphism correlate with recombination rates in D. melanogaster. Nature, 356(6369), 519-520. https://doi.org/10.1038/356519a0

Comeron, J. M. (2014). Background selection as baseline for nucleotide variation across the Drosophila genome. PLoS Genetics, 10(6), e1004434. https://doi.org/10.1371/journal.pgen.1004434

Marjoram, P., & Wall, J. D. (2006). Fast" coalescent" simulation. BMC genetics, 7, 1-9. https://doi.org/10.1186/1471-2156-7-16

McVicker, G., Gordon, D., Davis, C., & Green, P. (2009). Widespread genomic signatures of natural selection in hominid evolution. PLoS genetics, 5(5), e1000471. https://doi.org/10.1371/journal.pgen.1000471

Pouyet, F., & Gilbert, K. J. (2021). Towards an improved understanding of molecular evolution: the relative roles of selection, drift, and everything in between. Peer Community Journal, 1, e27. https://doi.org/10.24072/pcjournal.16

The long-distance transport and introduction of new species by humans is increasingly leading divergent lineages to interact, and sometimes interbreed, even after thousands or millions of years of separation. It is thus of prime importance to understand the consequences of these contemporary admixture events on the evolutionary fitness of interacting organisms, and their ecological implications.

Ciona robusta and Ciona intestinalis are two species of sea squirts that diverged between 1.5 and 2 million years ago and recently came into contact again. This occurred through human-mediated introduction of C. robusta (native to the Northwest Pacific) into the range of C. intestinalis (the English channeled Northeast Atlantic). In this study, Fraïsse et al. (2022) follow up on earlier work by Le Moan et al. (2021), who had identified a long genomic hotspot of introgression of C. robusta ancestry segments in chromosome 5 of C. intestinalis. The hotspot bears suggestive evidence of positive selection and the authors aimed to investigate this further using fully phased whole-genome sequences.

The authors narrow down on the exact boundaries of the introgressed region, and make a compelling case that it has been the likely target of positive selection after introgression, using various complementary approaches based on patterns of population differentiation, haplotype structure and local levels of diversity in the region. Using extensive demographic modeling, they also show that the introgression event was likely recent (approximately 75 years ago), and distinct from other tracts in the C. intestinalis genome that are likely a product of more ancient episodes of interbreeding in the past 30,000 years. Narrowing down on the potential drivers of selection, the authors show that candidate SNPs in the region overlap with the cytochrome family 2 subfamily U gene - involved in the detoxification of exogenous compounds - potentially reflecting adaptation to chemicals encountered in the sea squirt's environment. There also appears to be copy number variation at the candidate SNPs, which provides clues into the adaptation mechanism in the region.

All reviewers agreed that the work carried out by the authors is elegant and the results are robustly supported and well presented. In a round of reviews, various clarifications of the manuscript were suggested by the reviewers, including on the quality of the newly generated sequencing data, and some suggestions for qualifications on the conclusions reached by the authors as well as changes in the figures to increase their clarity. The authors addressed the different concerns of the reviewers, and the new version is much improved. 

This study into human-mediated introgression and its consequences for adaptation is, in my view, both well thought-out and executed. I therefore provide an enthusiastic recommendation of this manuscript.

References

Fraïsse C, Le Moan A, Roux C, Dubois G, Daguin-Thiébaut C, Gagnaire P-A, Viard F and Bierne N (2022) Introgression between highly divergent sea squirt genomes: an adaptive breakthrough? bioRxiv, 2022.03.22.485319, ver. 4 peer-reviewed and recommended by Peer Community in Evolutionary Biology. https://doi.org/10.1101/2022.03.22.485319

Le Moan A, Roby C, Fraïsse C, Daguin-Thiébaut C, Bierne N, Viard F (2021) An introgression breakthrough left by an anthropogenic contact between two ascidians. Molecular Ecology, 30, 6718–6732. https://doi.org/10.1111/mec.16189