Mutation is the raw material of evolution. Every generation, errors can occur when DNA is copied, repaired or rearranged. Most mutations are neutral or harmful, but a small number can alter traits in ways that affect survival and reproduction. The frequency at which these changes appear is known as the mutation rate, and it helps determine how quickly populations can respond to environmental pressures. A high mutation rate may supply genetic variation rapidly, while a low rate can preserve highly successful genetic combinations over long periods. Yet mutation rates are not fixed properties shared equally by all organisms. They can differ among species, populations, tissues and even stages of an organism’s life. The new research will examine whether reproductive mode is a major force shaping that variation.

Sexual reproduction creates offspring through the combination of genetic material from two parents, generally through meiosis and fertilization. This process reshuffles existing variants and can help populations purge harmful mutations or combine beneficial ones. Asexual reproduction, by contrast, produces offspring without the fusion of gametes, often generating genetically similar descendants from a single parent. Self-pollinating plants occupy an intermediate but distinctive position: they reproduce sexually, yet the pollen and ovules may originate from the same individual, limiting the genetic mixing associated with outcrossing. These differences affect population structure, effective population size, selection and the efficiency with which natural selection acts on new mutations. The researchers will test how these evolutionary conditions influence the long-term evolution of mutation rates themselves.

The University of Houston team will focus on Tetrahymena, microscopic freshwater organisms made up of single cells. These ciliates use hair-like structures called cilia to move through water and collect food, but their biology is far more complex than their size suggests. Tetrahymena possess distinct nuclear compartments and unusual life cycles, making them valuable systems for studying genome stability and evolutionary change. Previous work by Azevedo and Zufall found that Tetrahymena has the lowest mutation rate ever recorded in an organism. That finding raises an important biological puzzle. If mutation supplies the variation required for adaptation, how can a lineage with such an exceptionally slow rate of genetic change persist and evolve? The new study will investigate what evolutionary pressures and cellular mechanisms may have produced this extreme genomic stability.

Scientists at the University of Iowa will examine snails, while researchers at the University of Toronto will study mustard plants. Within each group, the investigators will compare closely related organisms that differ primarily in their reproductive strategies. This comparative design is intended to reduce the influence of confounding factors such as body size, generation time, ecological niche and genome architecture. By studying related species under carefully matched conditions, the team can ask whether differences in mutation rates track differences in reproductive mode. The researchers will combine empirical measurements with evolutionary modeling, allowing them to compare observed patterns with predictions about selection, genetic drift and the inheritance of mutation-rate modifiers.

Measuring mutation rates is technically demanding because most new mutations are rare and many are invisible at the level of appearance. A mutation may have no immediate effect on an organism’s growth, behavior or survival, particularly if it occurs in a noncoding region of the genome or is masked by another copy of the gene. Researchers therefore need large numbers of DNA sequences, carefully controlled breeding or culturing designs and statistical methods capable of distinguishing genuine inherited changes from sequencing errors. In organisms with short generation times, scientists can follow mutations across multiple generations. In others, they may compare parent-offspring genomes or use population-level genomic data to estimate how quickly variants accumulate. These approaches will help the collaborators determine not only how many mutations occur, but also when and where they arise.

The project’s theoretical component will be led by Azevedo, who will develop models to connect reproductive biology with the evolution of mutation rates. A central issue is the balance between the benefits and costs of genetic change. Mutations can generate useful variation, but most do not improve fitness and some are strongly damaging. Natural selection may therefore favor mechanisms that reduce copying errors and improve DNA repair. However, in rapidly changing environments, a greater supply of mutations may sometimes help populations discover advantageous traits. Reproductive mode can alter this balance by changing how mutations are exposed to selection, how quickly harmful variants are removed and how efficiently beneficial combinations spread. Modeling these processes across different organisms could reveal general principles that apply from single-celled species to plants and animals.

The researchers emphasize that the work is fundamental evolutionary biology, but its implications extend into medicine. Cancer provides a particularly important example because tumor cells reproduce clonally, a form of asexual expansion, as they divide within the body. Some tumors acquire elevated mutation rates through defects in DNA repair or replication, creating diverse subpopulations within the same mass of cancer cells. This genetic diversity can enable a tumor to survive changes in its environment, including exposure to chemotherapy or targeted drugs. Cells carrying mutations that confer treatment resistance may become more abundant, allowing the cancer to continue growing. Understanding how mutation rates evolve in asexual populations could therefore sharpen scientists’ understanding of tumor progression, although the project is not designed as an immediate clinical trial or treatment-development program.

The same evolutionary logic applies to infectious disease and antibiotic resistance. A microbial population exposed to a drug may contain, or rapidly generate, variants that tolerate the treatment. If those variants reproduce more successfully than susceptible cells, resistance can spread through the population. The speed and direction of that process depend on mutation, selection, population size and the movement of genes among organisms. By comparing mutation-rate evolution in systems with different reproductive modes, the NSF-supported collaboration may help clarify why some populations adapt rapidly while others remain genetically stable. Zufall said the group hopes to identify broad patterns rather than explain only the behavior of its chosen species. “We want to find broad patterns that underlie how populations evolve across all of life,” she said.

Azevedo described the collaboration as powerful because it brings together three experimental scientists working on different biological systems and a theoretician capable of integrating the results into a common framework. The project will not assume that sexual reproduction is universally superior or that asexual reproduction inevitably accelerates evolution. Instead, it will examine the conditions under which each strategy changes the costs and benefits of mutation. The findings could reshape how scientists think about genome stability, adaptation and the relationship between reproduction and genetic change. As Azevedo noted, understanding how mutation rates evolve may illuminate processes ranging from cancer and drug resistance to the broader capacity of living organisms to survive environmental change.

Subject of Research: The evolution of DNA mutation rates across organisms with sexual, asexual and self-pollinating reproductive modes.

Article Title: How Reproductive Strategies Shape the Speed of DNA Mutation

Web References: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2535706

Image Credits: University of Houston

Keywords: mutation rates, evolutionary biology, evolutionary genetics, genetic material, sexual reproduction, asexual reproduction, self-pollination, Tetrahymena, snails, mustard plants, genome stability, cancer evolution, antibiotic resistance, drug resistance, adaptive evolution, reproductive biology, microbial evolution