# Evolutionary Covariation > **Machine-Evolution Nexus:** [[articles/Digital Darwinism and the Invisible World of Machine Evolution|Digital Darwinism and the Invisible World of Machine Evolution]] places this node within the history and governance of substrate-independent evolution. **Domain:** Evolution / Structural Biology **Doc Type:** Canonical Wiki Node **Maturity:** Developed ## Definition Evolutionary covariation is correlated change among sequence positions across related lineages, often produced when interacting residues must change compatibly to preserve function. ## Nexus Context Protein-structure systems can use such statistical dependencies because descent and selection have tested combinations across deep time. ## Evidence Boundary Covariation can reflect phylogeny, sampling and indirect effects as well as direct contact. Models integrate it with other learned and structural information. ## Relationships [[wiki/Multiple Sequence Alignment|Multiple Sequence Alignment]], [[wiki/AlphaFold|AlphaFold]], [[wiki/Comparative Genomics|Comparative Genomics]], [[wiki/Scientific Inference|Scientific Inference]] ## Sources / Provenance - Direct-coupling and protein-covariation literature; Jumper et al. (2021).