Evolution of the lamin protein family: what introns can tell.

Lamins are the major components of the nuclear lamina, a filamentous layer found at the interphase between chromatin and the inner nuclear membrane. The lamina supports the nuclear envelope and provides anchorage sites for chromatin. Lamins and their associated proteins are required for most nuclear activities, mitosis, and for linking the nucleoskeleton to the network of cytoskeletal filaments. Mutations in lamins and their associated proteins give rise to a wide range of diseases, collectively called laminopathies. This review focuses on the evolution of the lamin protein family. Evolution from basal metazoans to man will be described on the basis of protein sequence comparisons and analyses of their gene structure. Lamins are the founding members of the family of intermediate filament proteins. How genes encoding cytoplasmic IF proteins could have arisen from the archetypal lamin gene progenitor, can be inferred from a comparison of the respective gene structures. The lamin/IF protein family seems to be restricted to the metazoans. In general, invertebrate genomes harbor only a single lamin gene encoding a B-type lamin. The archetypal lamin gene structure found in basal metazoans is conserved up to the vertebrate lineage. The completely different structure of lamin genes in Caenorhabditis and Drosophila are exceptions rather than the rule within their systematic groups. However, variation in the length of the coiled-coil forming central domain might be more common than previously anticipated. The increase in the number of lamin genes in vertebrates can be explained by two rounds of genome duplication. The origin of lamin A by exon shuffling might explain the processing of prelamin A to the mature non-isoprenylated form of lamin A. By alternative splicing the number of vertebrate lamin proteins has increased even further. Lamin C, an alternative splice form of the LMNA gene, is restricted to mammals. Amphibians and mammals express germline-specific lamins that differ in their protein structure from that of somatic lamins. Evidence is provided that there exist lamin-like proteins outside the metazoan lineage.