Asymmetric paralog evolution between the "cryptic" gene Bmp16 and its well-studied sister genes Bmp2 and Bmp4.

The vertebrate gene repertoire is characterized by "cryptic" genes whose identification has been hampered by their absence from the genomes of well-studied species. One example is the Bmp16 gene, a paralog of the developmental key genes Bmp2 and -4. We focus on the Bmp2/4/16 group of genes to study the evolutionary dynamics following gen(om)e duplications with special emphasis on the poorly studied Bmp16 gene. We reveal the presence of Bmp16 in chondrichthyans in addition to previously reported teleost fishes and reptiles. Using comprehensive, vertebrate-wide gene sampling, our phylogenetic analysis complemented with synteny analyses suggests that Bmp2, -4 and -16 are remnants of a gene quartet that originated during the two rounds of whole-genome duplication (2R-WGD) early in vertebrate evolution. We confirm that Bmp16 genes were lost independently in at least three lineages (mammals, archelosaurs and amphibians) and report that they have elevated rates of sequence evolution. This finding agrees with their more "flexible" deployment during development; while Bmp16 has limited embryonic expression domains in the cloudy catshark, it is broadly expressed in the green anole lizard. Our study illustrates the dynamics of gene family evolution by integrating insights from sequence diversification, gene repertoire changes, and shuffling of expression domains.