**This post is a part of the series on the 2019 AGA Presidential Symposium – Sex and Asex: the genetics of complex life cycles**
About the Author: Sarah McPeek is a PhD candidate in Evolution, Ecology, and Behavior with Dr. Butch Brodie at the University of Virginia in Charlottesville, VA. Her research focuses on the evolution of behavioral interactions among nectar-producing woodland wildflowers and nectar-foraging beetles at Mountain Lake Biological Station. Follow Sarah’s work @sarahjmcpeek and read more science writing at sarahjmcpeek.com.
First, a confession: I hang my sun-beaten field hat on the quantitative geneticist’s peg. I like measuring things that I can see, hear, smell, taste, and touch. In my camp, adaptation is a kinetic process shaped by a shifting balance of ecological forces tugging on the phenotype. We don’t worry too much about Sewall Wright’s adaptive landscape of infinite genetic potential. Give me a guinea pig or a flower with colors I can measure and phenotypic variance components I can partition. The genes controlling these traits are mainly additive, dominant, and epistatic abstractions. And yet, if I breed those guinea pigs, I may never recover the same fur phenotype again. And if I allow those flowers to propagate clonally for many generations, their offspring may grow feeble, wilt, lose their color, and die far too young. To understand why, I need to dig deeper into the structures underlying these traits. Dr. Sally Otto’s 2021 perspective is an important reminder that genetic architecture sets important limits on phenotypic adaptation.
As abstract as the name “hereditary unit” may seem, genes are physical structures. Individual genes are bound together by phosphodiester bonds and wound around proteins inside the nuclei of gametes that may never fuse to form new genetic possibilities. Until they do, a population’s adaptive potential is heavily constrained by rigid chromosomal scaffolding. Selection acts on the phenotypic products of this tangled amalgam of alleles. A few of these alleles are beneficial, but the vast majority run the gamut from nearly neutral to horribly bad. Thus, rare helpful mutations may be crushed by hordes of flanking genes with harmful fitness effects, while harmful mutations may be embraced by neighboring genes with benign or positive fitness effects. Dominant and epistatic interactions within and among these neighborhoods can mask the effects of individual alleles, further swamping selection’s ability to weed out the good from the bad. Otto (2021) argues that meiotic sex breaks down outdated genetic scaffolding and breaks up shoddy associations so new structures can rise and fall by natural selection. Selective interference, she asserts, istheexplanation for the evolution of sex.
Otto (2021) uses selective interference as her preferred term for a phenomenon that encompasses a range of classical and modern genetic theories including the Fisher-Muller hypothesis, Muller’s Ratchet, clonal interference, “ruby-in-the-rubbish,” and genetic draft. Several of these ideas formed in the pre-genomics era, back when genes truly were abstract hereditary units with some unknown chemical basis. Even if it was all bean bag genetics in those days, early geneticists were astoundingly near the mark on the possible causes and consequences of selective interference. Specifically, they recognized that recombination was an essential mechanism for breaking apart harmful allelic associations that accumulate on chromosomes through chance local mutations combined with selection and random drift. Without sex and recombination, there are only ever a few genetic scaffolds available for selection to act on. By rearranging the surviving scaffolds, sex and recombination allow an almost limitless number of genetic combinations, increasing the likelihood of finding a solid adaptive foundation for selection to reinforce and for future mutation and recombination to enhance. Hence, sex and recombination can speed the rate of adaptation, rocketing a population up its fitness peak as selection fixes helpful alleles and eliminates harmful ones. Of course, recombination could just as well shove alleles from helpful combinations into worse scaffolds. Thus, theory recognizes that too much scaffold rearrangement can also wreck selection’s progress.
The probabilistic nature of recombination and sex may explain why most species exist in a “gray area” between fully sexual and fully asexual. For decades, Ottoand other geneticists have used gray area species to search for evidence of selective interference as the catalyst for the evolution of sex. For instance, experiments with sexual and asexual strains of yeast show that sexual lineages adapt much slower to new environments than asexual lineages (e.g., Colegrave 2002). Further, these differences appear to be due to their rates of recombination rather than other pleiotropic benefits of sex such as the repair of age-induced DNA damage (e.g., Goddard et al. 2005, Gray and Goddard 2012). Genomic data from these experimental evolution studies also confirm adaptation on a genetic level, finding that clonal yeast strains fix large cohorts of mutations with all kinds of fitness effects while sexual yeast strains fix far fewer harmful mutations and far more helpful ones (McDonald et al. 2016). Recent studies of molecular adaptation across the genomes of many species also document patterns linked to recombination on an intragenomic scale: chromosomal segments with lower recombination rates but higher gene densities and higher mutation rates are often missing large proportions of adaptive substitutions (e.g., Castellano et al. 2016, Uricchio et al. 2019). All these experimental and observational data support theoretical predictions about the existence, persistence, and significance of selective interference for setting the pace of adaptive evolutionary change in sexual and asexual lineages.
Intriguingly, gene function can interact with gene position to modulate the strength of selective interference in both sexual and asexual species. Some of these modifier genes, which Ottocalls mutators, increase the local mutation rates of other nearby genes. Mutators speed the accumulation of helpful alleles and are thus likely to be favored by selection in asexual lineages where adaptation is typically slower. However, they are just as likely to speed the accumulation of harmful alleles, lowering the average fitness of an asexual lineage. Other genes modify rates of recombination and sexual reproduction. Recombination rate modifiers weaken selective interference, but this comes at a cost. Because they increase local recombination, modifier alleles are often recombined in new allelic combinations themselves, which can speed the fracturing of beneficial as well as harmful genetic associations. Hence, adaptation strikes a delicate balance between the extrinsic actions of selection, drift, and gene flow that build up existing scaffolding and the intrinsic actions of gene-mediated sex and recombination that tear scaffolding down.
The evolution of sex is a foundational question in biology that touches the work of all geneticists, myself included. Whether or not you study reproductive dynamics, Otto’s perspective reminds us all that genetic scaffolding is the cornerstone of adaptation. Moreover, her work is a resounding call to action for all geneticists: theoretical, computational, population, phylogenomic, molecular, ecological, and yes, even quantitative geneticists, to play our part in piecing together selective interference as the strongest potential explanation for sex. Ottooutlines many exciting future questions to explore across wild, laboratory-reared, and computer-generated populations. On a molecular scale, for instance, we need to understand more about what modifier genes are and how they function in changing local genetic scaffolding. On an ecological scale, we need to know how migration between populations may contribute to or alternatively counteract selective interference within populations. Working together, Otto believes we can use the many tools at our disposal: strong theoretical grounding, precise genomic technologies, and clever evolutionary experiments, to disentangle the puzzle of sex once and for all.
Castellano, D., Coronado-Zamora, M., Campos, J. L., Barbadilla, A., & Eyre-Walker, A. (2016). Adaptive evolution is substantially impeded by Hill–Robertson interference in Drosophila. Molecular biology and evolution. 33(2): 442-455.