Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. All proteins containing these repeats are thought to be involved in protein-protein inter-actions. The crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to pa structural units. These units are arranged so that they form a parallel P-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglobular shape. These two features may be responsible for the proteinbinding functions of proteins containing leucine-rich repeats. are commonly spaced by 3, 4 or 7 residues.

AbGUt half of the genes encoding the known LRR-containing proteins have been sequenced. Gonadotrophin receptor genes contain several similarly sized exons in their LRR domains that are homologous in their exon-intron junction sequences3, suggesting that the LRR domain evolved by exon duplication and shuffling from a single prototypic exon corresponding to one LRR. Such an evolutionary relationship is less obvious in genes encoding other LRR-containing proteins, but the introns often localize at similar positions in the repeats (most frequently between positions 1 and 6, less frequently between positions II and 18, and rarely elsewhere). The most likely mechanism of evolution of LRR-containing proteins would therefore comprise unequal crossovers and duplications of gene fragments corresponding to prototypic leucine-rich building blocks. Two evolutionary scenarios are possible:(1) an ancestral LRR module evolved first, and duplicated to give rise to individual members of the superfamily that later developed their own unique consensus sequences; or (2) the duplications occurred separately in each protein family and, owing to structural constraints, gave rise to similar, but unique, consensus sequences. These two schemes are not mutually exclusive and there is good reason to believe that the divergent and convergent scenarios have worked in conjunction to yield the LRR superfamily that exists today. The variation in the length of LRRs among proteins and the