Evolutionary History of the ADRB2 Gene in Humans

Abstract

First paragraph: To the Editor: Recently, Cagliani et al.1 reported on the evolutionary history of the human β2-adrenoreceptor gene (ADRB2 [MIM 109690]). The authors presented their analysis of the genealogy of inferred ADRB2 haplotypes reconstructed through the use of a median-joining network approach. ADRB2 shows a high level of polymorphism, including three coding variants with altered functional properties (at codons 16, 27, and 164, hereafter referred to as C16, C27, and C164), and several suspected regulatory variants. The network presented by Cagliani et al.1 was prepared with software implementing a model that assumes no recombination but allows for recurrent mutation. We notice that most SNPs in their network are represented by recurrent mutations in nonreticulated parts of the network, which we find biologically implausible and difficult to interpret in an evolutionary context. We have prepared a network diagram for the evolution of common ADRB2 haplotypes that can be accounted for by divergence via the accumulation of mutations and rare recombination events between diverged haplotypes (Figure 1). This revised network requires no recurrent mutations (homoplasy) and accounts for the major haplotype groups of Cagliani et al., Hawkins et al., and Drysdale et al., as well as those revealed by the HapMap data, with only one recombination event.