Blood, 1 April 2003, Vol. 101, No. 7, pp. 2451-2451
Fishing for evolutionary clues to globin gene regulation
The pufferfish has a compact genome that is well suited for
finding many protein-coding genes by fish-mammal sequence comparison. In this issue Gillemans and colleagues (page 2842) also turn to pufferfish for insights into the evolution and function of long-range regulatory elements, such as the locus control region (LCR) found upstream of mammalian beta-globin genes and the major regulatory element (MRE) found upstream of mammalian and avian alpha-globin genes.
They find that matters are more complex than anticipated, but they also
uncover clues that may prove productive in the long run. Pufferfish
have 2 globin-gene loci, one with only alpha-globin genes (Flint et
al, Hum Mol Genet. 2001;10:371-382) and one with an active beta-globin
gene plus an active and a likely inactive alpha-globin gene (the
alpha/beta locus). Gillemans et al searched the latter for a long-range
regulatory element similar to a mammalian LCR, but none was found by
sequence searches, DNase hypersensitive site mapping, or gene transfer
into transgenic mice. Thus, either pufferfish do not have a regulatory
element similar to the mammalian beta-globin LCR, or it is considerably
further away on the chromosome. Interestingly, detailed analysis of the
genes flanking the pufferfish globin loci showed a homologue to the
Rhomboid gene of Drosophila close to the globin
genes in both loci, as well as upstream to the human alpha-globin
genes and close to a recently discovered, widely expressed globin
gene (encoding cytoglobin) on human chromosome 17. This
Rhomboid-globin gene arrangement appears to be
ancient, predating the gene duplications leading to the genes encoding hemoglobins. Such conservation of synteny and breaks from it
likely will be helpful guides to better understanding the
evolution of globin gene families and deriving clearer insight into the
origins of long-range regulatory elements.
Ross C. Hardison
The Pennsylvania State University
