Patterns of recombination in snakes reveal a tug-of-war between PRDM9 and promoter-like features

Abstract

In some mammals, notably humans, recombination occurs almost exclusively where the protein PRDM9 binds, whereas in vertebrates lacking an intact PRDM9 , such as birds and canids, recombination rates are elevated near promoter-like features. To determine whether PRDM9 directs recombination in nonmammalian vertebrates, we focused on an exemplar species with a single, intact PRDM9 ortholog, the corn snake ( Pantherophis guttatus ). Analyzing historical recombination rates along the genome and crossovers in pedigrees, we found evidence that PRDM9 specifies the location of recombination events, but we also detected a separable effect of promoter-like features. These findings reveal that the uses of PRDM9 and promoter-like features need not be mutually exclusive and instead reflect a tug-of-war that is more even in some species than others.

Increased Positive Selection in Highly Recombining Genes Does not Necessarily Reflect an Evolutionary Advantage of Recombination

“…Of note, those hotspot still remain long enough so that they leave a clear gBGC footprint in substitutions across mammals ( Berglund et al 2009 ; Galtier et al 2009 ; Ratnakumar et al 2010 ; Clément and Arndt 2013 ; Lartillot 2013 ; Lesecque et al 2014 ; Galtier 2021 ). On the other hand, many species including most placental mammals, passerine birds, colubroid snakes, budding yeasts and many angiosperm plants exhibit recombination hotspots in 5’ of genes that are relatively long-lived ( Axelsson et al 2012 ; Choi and Henderson 2015 ; Singhal et al 2015 ; Lam and Keeney 2015 ; Kawakami et al 2017 ; Schield et al 2020 ; Hoge et al 2023 ; Joseph et al 2023 ). Interestingly, in mammals these recombination hotspots coevolve slowly with DNA methylation ( Joseph et al 2023 ).…”

Understanding the Genetic Basis of Variation in Meiotic Recombination: Past, Present, and Future

“…This may result in an “arms race” scenario to replenish hotspots through selection for new sequence motifs ( Ubeda and Wilkins 2011 ; Latrille et al 2017 ), and indeed, in species where PRDM9 is likely to be functional, it is one of the most rapidly evolving genes in the genome ( Baker et al 2017 ). The diversity of the PRDM9 ZF array within species can be remarkable and may reflect variation in their binding affinities to different motifs; over 150 alleles have been identified in wild mice ( Vara et al 2019 ; Wooldridge and Dumont 2023 ), 69 alleles in humans ( Alleva et al 2021 ), and even 22 alleles identified in 19 corn snakes in a single study ( Hoge et al 2024 ).…”

“…At the time of writing, insights into the ubiquity and relative importance of PRDM9-mediated hotspots are still emerging. PRDM9 was first shown to be the major driver of hotspot positioning in humans and mice ( Baudat et al 2010 ), and there is now evidence that it is associated with hotspots in nearly all mammals, some teleost fish, turtles, snakes, and lizards ( Baker et al 2017 ; Schield et al 2020 ; Hoge et al 2024 ; Raynaud et al 2024 ); there is also emerging evidence that PRDM9 may direct hotspot positioning in some insects ( Everitt et al 2024 ). However, PRDM9 function has been lost in some groups, such as canids, birds, crocodiles, and amphibians ( Baker et al 2017 ), which have reverted back to the stable, ancestral hotspots enriched at functional elements ( Singhal et al 2015 ).…”

“…A recent investigation of hotspots in 52 mammal species showed that many species in fact use both PRDM9-mediated and PRDM9-independent (i.e. ancestral) hotspots ( Joseph et al 2024 ), and that this is also likely to be the case in rattlesnakes and corn snakes ( Schield et al 2020 ; Hoge et al 2024 ).…”