The field of molecular evolution investigates the mechanisms and consequences of the evolution of macromolecules—particularly nucleic acids (DNA and RNA) and proteins. Molecular evolutionists study relationships between the structures of genes and proteins and the functions of organisms. They also examine molecular variation to reconstruct evolutionary history and to study the mechanisms and consequences of evolution. Students of this field ask questions such as: What does molecular variation tell us about a gene’s function? Why do the genomes of different organisms vary in size? What evolutionary forces shape patterns of variation among genomes? And a crucial question from an evolutionary perspective: How do genomes acquire new functions? Investigations into the evolution of particular nucleic acids and proteins are instrumental in reconstructing the evolutionary histories of genes. Ultimately, molecular evolutionary biologists hope to explain the molecular basis of biological diversity.

The evolution of nucleic acids and proteins depends on genetic variation introduced by mutations. One of several ways in which genes evolve is by means of nucleotide substitutions (the incorporation of point mutations in populations). In genes that encode proteins, nucleotide substitutions sometimes result in amino acid replacements that can change the charge, the structure, and other chemical and physical properties of the encoded protein. These changes in a protein molecule often affect the way that protein functions in the organism.

Evolutionary changes in genes and proteins can be identified by comparing nucleotide or amino acid sequences from different organisms. The longer two sequences have been evolving separately, the more differences they accumulate (bearing in mind that different genes in the same species evolve at different rates). Determining how long ago changes in nucleotide or amino acid sequences occurred is a useful step toward inferring their causes. Knowledge of the pattern and rate of evolutionary change in a given macromolecule is useful in reconstructing the evolutionary history of groups of organisms.

To compare genes or proteins from different organisms, biologists need a way to identify homologous parts of macromolecules. (Recall from Key Concept 21.1 that homologous features are those shared by two or more species that have been inherited from a common ancestor.) Homologous parts of a protein can be identified by their homologous amino acid sequences. And since nucleotide sequences encode amino acid sequences, the concept of homology extends down to the level of individual nucleotide positions. Therefore one of the first steps in studying the evolution of genes or proteins is to align homologous positions in the amino acid or nucleotide sequence of interest.