Mutation rate is central to understanding evolution

Abstract

Darwinian evolution relies on mutation as a constant source of variation, yet in evolutionary biology, mutation is often taken for granted, pushed to the background and treated as if it was random and uniform across all genes and all species. Mutation is an essential parameter in many evolutionary models, although often regarded as a “nuisance parameter” rather than the focus of interest—but mutation is a fundamental driver of evolution. Studying how rates and patterns of mutation are shaped by chance and selection is critical for understanding evolution of biodiversity, and has practical consequences for the way we use DNA to understand evolutionary history. Many evolutionary analyses—including genomics, population genetics, and phylogenetics—make simplifying assumptions about mutation rate, and the nature of these assumptions can influence the answers we get (e.g., Ritchie et al., 2022).

Mutation rate is a balancing act, playing out at many different evolutionary levels simultaneously. At the biochemical level, single-base changes to DNA sequences result from replication errors or imperfectly repaired damage. Cells have an impressive arsenal of equipment for repairing damage and correcting errors, but repair must be “paid for” in energy and time, which could otherwise be invested in growth and reproduction (Avila and Lehmann, 2023). Individuals can vary in repair efficiency, or in the amount of energy available to invest in repair, and therefore in their patterns and rates of mutation. On longer timescales, lineage persistence depends on finding a balance between risk of mutation and costs of error correction and repair. Undirected changes to functional sequences are typically more likely to ruin than improve, so mutation is expected to exact a cost in terms of chances of success. If mutation rate is too high, offspring might not reliably inherit their parents’ advantageous traits, yet mutation provides the chance of generating variations that might allow individuals to better survive in a changing environment or have an increased chance of avoiding parasites and predators. If there is too little mutation, evolution grinds to a halt. If there is too much mutation, it runs into the ground, scrambling the hereditary message passed to subsequent generations and overwriting adaptations. The relative risks and benefits of mutation may vary between lineages and depend upon the environment, shifting when a lineage must adapt to changing conditions (Weng et al., 2021). Mutation rates are a balance between the chance of beneficial variation and the risk of destroying key genome functions. This balancing act plays out in individual lives and over evolutionary time.

Mutation rate is governed by the rate at which changes happen to the genome and the rate at which they are repaired, both of which vary among organisms. Considering one universal mutagen—ultraviolet (UV) light—provides a useful illustration. UV light can damage the DNA double-helix and affect the base sequence by causing two adjacent pyrimidines to pair with each other instead of pairing with bases on the opposite strand. Pyrimidine dimers have two critical effects: firstly, disrupting pairing ruins the information coding capacity of DNA; secondly, by causing an awkward bump in the helix, dimers block the movement of enzymes that copy and transcribe DNA. If the dimer is not repaired, DNA cannot be copied or expressed (Banaś et al., 2020). To avoid this disaster, cells have a range of repair responses to UV damage—from specialist repair enzymes that reverse the damage, to general mismatch repair equipment that excise and replace damaged bases, to the last-ditch “SOS response” that uses any available means to get past the block and continue to copy. One might expect plant lineages that grow where UV radiation is high will have higher mutation rates, but they don't (Bromham et al., 2015). Individual plants exposed to increased UV radiation suffer more damage, but in response, they might increase investment in DNA protection and repair (Ries et al., 2000). An individual better able to repair UV damage is more likely to be able to reproduce in a high UV environment, so populations living with high UV exposure can evolve mutation avoidance mechanisms or better DNA repair. Lineages will only persist if they can successfully reproduce under the prevailing conditions. It seems likely that mutation rate does not correlate with environmental UV levels because DNA repair level is scaled to the level of exposure, matching investment to relative risk.

This balancing act between mutation and repair also applies to DNA replication errors. Every cell division generates copy errors, so plants accumulate mutations as they grow. Nonlethal mutations can be passed on in growing cell lines, and if incorporated into reproductive structures or clonally reproducing tissue, these “somatic” mutations can make their way into new individuals, adding genetic variation to the population (Gross et al., 2012). Accumulation of somatic mutations leads to genetic variation within individuals, between individuals, and between lineages (Schoen and Schultz, 2019). Growing branches accumulate different mutations, so the number of genetic differences between tips depends on both branch length and age (Orr et al., 2020). Roots accumulate fewer somatic mutations, possibly because they go through fewer cell divisions (Wang et al., 2019). Ramets of clonally producing plants accumulate genetic changes, introducing genetic variation between parts of the growing colony (Yu et al., 2020). The process of genetic divergence is continuous at all levels of organisation: cell, individual, population, and lineage.

Copy errors are shaped by the same balancing act as the repair of extrinsic DNA damage. Accurate copying requires investment in error correction, taking time and resources that could be invested in reproduction, so investment should scale with the costs and benefits of mutation avoidance. Investment in mutation avoidance can be dependent on individual condition, so mutation rate can increase in an individual under stress (Quiroz et al., 2023). Male and female gametes have different mutational profiles, with more mutations transmitted through pollen than ovules—a pattern that could be explained by a greater number of cell divisions in the paternal line, or differences in DNA repair patterns and rates, or because pollen is exposed to more mutagens like UV light (Whittle and Johnston, 2002). Replication error rates vary within individuals, with evidence for a higher mutation rate per cell division in “disposable” cell lines, such as petals, compared to cell lines that are longer-lived or may give rise to reproductive tissue (Wang et al., 2019). Longer-lived plants have reduced rates of mutation, due to both reduced cell division rates and increased investment in DNA repair in meristem tissue (Burian, 2021).

Rate of mutation accumulation is shaped by both chance (opportunity for mutation) and selection (investment in mutation avoidance) and the evolutionary consequences play out at individual, population, and lineage levels. Accumulation of mutations influences reproductive strategies, driving genetic incompatibility both within and between individuals. Mutations occurring along different branches of long-lived individuals can lead to a greater range of fitness in offspring from different parts of the plant, due to both beneficial and deleterious somatic mutations (Cruzan et al., 2022), but types and patterns of mutations can vary between lineages (López-Cortegano et al., 2021). The same process can occur in vegetative reproduction in short-lived plants—for example, number of phenotypically noticeable mutations in buttercups increases with age of the meadow, as does the percentage of nonviable pollen (Warren, 2009). This process of mutation accumulation with growth can drive clonal divergence between parts of an individual or generate genetically varying individuals in a vegetatively reproducing population (Yu et al., 2020). Somatic mutations supply genetic variation but also drive incompatibility within and between individuals, reducing the capacity for sexual reproduction and locking lineages into short-term advantages of asexual reproduction at the expense of longer-term evolutionary persistence (Gross et al., 2012). Mutation accumulation in long-lived individuals reduces genetic compatibility between individuals in a population, which may ultimately drive divergence into noninterbreeding populations (Lesaffre, 2021), flowing through to macroevolutionary levels of diversification (Marie-Orleach et al., 2024). Plant families with higher mutation rates are more species rich, a pattern that may be driven by increased rate of accumulation of genetic incompatibility between populations (Bromham et al., 2015).