RESUMO
The alpha- and beta-globin gene families of jawed vertebrates have diversified with respect to both gene function and the developmental timing of gene expression. Phylogenetic reconstructions of globin gene family evolution have provided suggestive evidence that the developmental regulation of hemoglobin synthesis has evolved independently in multiple vertebrate lineages. For example, the embryonic beta-like globin genes of birds and placental mammals are not 1:1 orthologs. Despite the similarity in developmental expression profiles, the genes are independently derived from lineage-specific duplications of a beta-globin pro-ortholog. This suggests the possibility that other vertebrate taxa may also possess distinct repertoires of globin genes that were produced by repeated rounds of lineage-specific gene duplication and divergence. Until recently, investigations into this possibility have been hindered by the dearth of genomic sequence data from nonmammalian vertebrates. Here, we report new insights into globin gene family evolution that were provided by a phylogenetic analysis of vertebrate globins combined with a comparative genomic analysis of three key sauropsid taxa: a squamate reptile (anole lizard, Anolis carolinensis), a passeriform bird (zebra finch, Taeniopygia guttata), and a galliform bird (chicken, Gallus gallus). The main objectives of this study were 1) to characterize evolutionary changes in the size and membership composition of the alpha- and beta-globin gene families of tetrapod vertebrates and 2) to test whether functional diversification of the globin gene clusters occurred independently in different tetrapod lineages. Results of our comparative genomic analysis revealed several intriguing patterns of gene turnover in the globin gene clusters of different taxa. Lineage-specific differences in gene content were especially pronounced in the beta-globin gene family, as phylogenetic reconstructions revealed that amphibians, lepidosaurs (as represented by anole lizard), archosaurs (as represented by zebra finch and chicken), and mammals each possess a distinct independently derived repertoire of beta-like globin genes. In contrast to the ancient functional diversification of the alpha-globin gene cluster in the stem lineage of tetrapods, the physiological division of labor between early- and late-expressed genes in the beta-globin gene cluster appears to have evolved independently in several tetrapod lineages.
Assuntos
Família Multigênica/genética , Filogenia , Vertebrados/genética , alfa-Globinas/genética , Globinas beta/genética , Animais , Teorema de Bayes , Aves/genética , Galinhas/genética , Evolução Molecular , Genoma/genética , Funções Verossimilhança , Lagartos/genética , Homologia de Sequência do Ácido NucleicoRESUMO
Drosophila tracheal terminal branches are plastic and have the capacity to sprout out projections toward oxygen-starved areas, in a process analogous to mammalian angiogenesis. This response involves the upregulation of FGF/Branchless in hypoxic tissues, which binds its receptor Breathless on tracheal cells. Here, we show that extra sprouting depends on the Hypoxia-Inducible Factor (HIF)-alpha homolog Sima and on the HIF-prolyl hydroxylase Fatiga that operates as an oxygen sensor. In mild hypoxia, Sima accumulates in tracheal cells, where it induces breathless, and this induction is sufficient to provoke tracheal extra sprouting. In nontracheal cells, Sima contributes to branchless induction, whereas overexpression of Sima fails to attract terminal branch outgrowth, suggesting that HIF-independent components are also required for full induction of the ligand. We propose that the autonomous response to hypoxia that occurs in tracheal cells enhances tracheal sensitivity to increasing Branchless levels, and that this mechanism is a cardinal step in hypoxia-dependent tracheal sprouting.