Figure 3.

Evolution of the midkine/pleiotrophin family by block duplications in vertebrates. Broken lines represent the evolutionary relationships between Mdk and Ptn sequences indicated by phylogenetic analysis (Fig. 2). Duplication 1 arose before divergence of tetrapods and fish; duplication 2 was fish specific. Duplicates that are not mentioned either have not been identified in the databases or have been lost during evolution. For simplicity, gene order has been kept in the different lineages; nonrelevant intervening genes have been omitted, and the distances between loci are not at scale. Mapping information has been obtained from the drafts of the genomes of Homo sapiens (http://www.ncbi.nlm.nih.gov/BLAST/), Takifugu rubripes (fugu) (http://fugu.hgmp.mrc.ac.uk/) and Danio rerio (zebrafish) (http://www.ensembl.org/Danio_rerio/blastview), as well as from the zebrafish genetic maps (http://zfin.org/cgi-bin//mapper_select.cgi).