Molecular Evolution

Molecular evolution examines how DNA, RNA and protein sequences change over time under the influence of mutation, selection, drift and recombination. Variation arises through replication errors and chemical damage, then becomes fixed by genetic drift or driven to higher frequency by adaptive selection. Analyses of sequence divergence underpinned the discovery of the molecular clock, a near-constant rate of neutral substitutions over time, and inspired the neutral theory, which posits that the bulk of molecular change has negligible fitness effect. Subsequent refinement by the nearly neutral theory recognised that slightly deleterious variants may drift to fixation in small populations and that substitution rates reflect the balance between mutation supply, selective constraint and population size. Advances in high-throughput sequencing enable phylogenomic reconstruction from hundreds of loci or whole genomes, permitting inference of divergence times, adaptive landscapes and coevolutionary processes such as mitonuclear interactions. Molecular evolution integrates comparative data with population-genetic models to reveal the genetic basis of species diversity, adaptive change and the tempo of diversification across the Tree of Life.

Research from Nature Portfolio

Studies have revealed a lethal mitonuclear incompatibility in hybrid fish, where mismatched nuclear and mitochondrial complex I subunits impair enzyme assembly and cause juvenile mortality or embryonic arrest. Heterozygous hybrids retain partial complex I function but exhibit proteome imbalance, demonstrating non-additive genetic architecture in post-zygotic barriers. Genome analyses of paralogous energy-metabolism genes show accelerated divergence and historical transfers of incompatibilities between species. Meanwhile, a deep-time re-analysis of plant genomic data across 25 angiosperms identifies 108 gene families whose allele frequencies covary with temperature and precipitation, far more than expected by chance. These climate-associated orthogroups display high pleiotropy and centrality in co-expression networks, suggesting that broadly expressed regulators underlie recurrent climate adaptation over 300 Myr of divergence.

Research from all publishers

A novel comparative method (CEGA) exploits polymorphism and divergence data from paired human and chimpanzee loci to detect both balancing and positive selection, outperforming existing tests, especially in non-coding regions, and revealing selection on brain-related pathways. In wild mice, “pathometagenomics” linked a blood-vessel-specific allele of the glycosyltransferase gene B4galnt2 to resistance against an opportunistic Morganella pathogen, uncovering a trade-off between bleeding time and infection susceptibility maintained by long-term balancing selection. In a widespread shrub, two deeply divergent alleles of an R2R3 MYB transcription factor control red versus white twig trichome colour and persist as a balanced polymorphism through spatially varying selection, despite homogenising gene flow elsewhere in the genome.

Molecular Evolution publication trend

The graph below shows the total number of articles in molecular evolution across all publications each year (not limited to Nature Index journals).

Technical terms

Molecular clock: The hypothesis that neutral substitutions accumulate at an approximately constant rate, permitting estimation of divergence times.

Mitonuclear incompatibility: A deleterious epistatic interaction between nuclear and mitochondrial gene variants, disrupting mitochondrial function.

Balancing selection: Natural selection maintaining two or more alleles at a locus above neutral expectation through heterozygote advantage, frequency dependence or varying environments.

Orthogroup: A set of genes in different species descended from a single ancestral gene in their last common ancestor.

Phylogenomic analysis: Reconstruction of evolutionary relationships using genome-scale sequence data across multiple loci.

Epistasis: A non-additive interaction between alleles at different loci, where the effect of one allele depends on the genotype at another.

References

1. A lethal mitonuclear incompatibility in complex I of natural hybrids. Nature (2024).
2. The genetic architecture of repeated local adaptation to climate in distantly related plants. Nature Ecology & Evolution (2024).
3. CEGA: a method for inferring natural selection by comparative population genomic analysis across species. Genome Biology (2023).
4. Pathometagenomics reveals susceptibility to intestinal infection by Morganella to be mediated by the blood group-related B4galnt2 gene in wild mice. Gut Microbes (2023).
5. Balancing selection on an MYB transcription factor maintains the twig trichome color variation in Melastoma normale. BMC Biology (2023).
6. Causes of Variation in the Rate of Molecular Evolution.