One of the steps in the evolution of tetrapod limbs was the loss of the distinctive fringe of fin rays and fin folds found in the fins of fishes. It is now shown that two novel proteins, actinodin 1 and 2, are essential structural components of fin rays and fin folds in zebrafish, and are also encoded in the genomes of other teleost fish and at least one species of shark, but not in tetrapods. It is suggested that the loss of these genes may have contributed to the fin-to-limb transition in tetrapod evolution.

Sialic acid acetylesterase (SIAE) is an enzyme that is involved in B-cell activation and is required to maintain immunological tolerance in mice. It is shown here that rare, inherited and functionally defective SIAE variants are associated with a variety of autoimmune diseases in humans. The study provides one of the first examples of the importance of rare genetic variants in complex diseases, such as those involving autoimmunity.

The methylation of DNA in 5? promoter regions suppresses gene expression, but what is the role of DNA methylation in the bodies of genes? Here, a map of DNA methylation is generated from human brain tissue; it is found that most methylated CpG islands are within intragenic and intergenic regions, rather than within promoters. It is proposed that intragenic methylation regulates the expression of alternative gene transcripts in different tissues and cell types.