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We sequenced beta-fibrinogen intron 7 (beta-fibint 7) from 28 species of birds, representing 18 families in nine orders. Although the antiquity of the avian orders is estimated to be 55 to 90 Myr, and numerous indels have accrued among diverging lineages, the intron sequences were not difficult to align. However, alignment of avian sequences with mammal or snake sequences was difficult, and the residual phylogenetic signal was weak. beta-fibint 7 is an AT-rich intron, and its base composition varies little over the diversity of birds represented by our sample. Alignment of these anciently diverged sequences reveals at least five clusters of conserved nucleotides; at least two clusters appear to be in excess of the minimal set usually associated with intron excision, but their functions are unknown. Two equally most-parsimonious (MP) trees were found when indels were not included in the phylogenetic analysis, and six such trees were found when indels were included. The Neighbor-Joining and maximum-likelihood trees were identical to each other and to one of the MP trees in each MP analysis. Indels, as well as nucleotide substitutions, are phylogenetically informative, and bootstrap support exceeded 90% for 21 of 24 inferred nodes when indels were included in the MP analysis. All traditional orders represented by two or more species appear monophyletic. Relationships among avian orders are strongly supported with the exception of an inferred sister-group relationship between Caprimulgiformes and Columbiformes. A relatively close relationship between Piciformes and Passeriformes is inferred, at odds with earlier DNA-DNA hybridization studies but consistent with traditional classifications. Among Passeriformes, the traditional perspective of a sister-group relationship of suboscines and oscines is supported, as is the subsequent split of the oscines into a lineage representative of the Corvida before the diversification of the Passerida. The four species of owls divide into two strongly supported clades, corresponding to the widely accepted bifurcation of owls into two families, Tytonidae and Strigidae. A sister-group relationship between gallinaceous birds and waterfowl, the Galloanserae, is also strongly supported.

Folate deficiency has been shown to influence carcinogenesis by creating an imbalance in the base excision repair (BER) pathway impacting BER homeostasis. The inability to mount a BER response to oxidative stress in a folate deficient environment results in the accumulation of DNA repair intermediates, i.e., DNA strand breaks. Our data indicate that upregulation in β-pol expression in response to oxidative stress is inhibited by folate deficiency at the level of gene expression. Alteration in expression of β-pol in a folate deficient environment is not due to epigenetic changes in the core promoter of the β-pol gene, i.e., the CpG islands within the β-pol promoter remain unmethylated in the presence and/or absence of folate. However, the promoter analysis studies show a differential binding of regulatory factor(s) to the −36 to −7 region (the folic acid response region, FARR) within the core promoter of β-pol. Moreover, we observe a tight correlation between the level of binding of regulatory factor(s) with the FARR and inhibition of β-pol expression. Based on these findings, we propose that folate deficiency results in an upregulation/stability of negative regulatory factor(s) interacting with FARR, repressing the upregulation of the β-pol gene in response to oxidative stress.

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Phylogenetic inferences drawn from comparative data on mammalian ␤-globin gene clusters indicate that the ancestral primate cluster contained a locus control region (LCR) and five paralogously related ␤-type globin loci (5 -LCR--␥--␦-␤-3 ), with and ␥ expressed solely during embryonic life. A ␥ locus tandem duplication (5 -␥ 1 -␥ 2 -3 ) triggered ␥'s evolution toward fetal expression but by a different trajectory in platyrrhines (New World monkeys) than in catarrhines (Old World monkeys and apes, including humans). In platyrrhine (e.g., Cebus) fetuses, ␥ 1 at the ancestral distance from is down-regulated, whereas ␥ 2 at increased distance is up-regulated. Catarrhine ␥ 1 and ␥ 2 acquired longer distances from (14 and 19 kb, respectively), and both are upregulated throughout fetal life with ␥ 1 's expression predominating over ␥ 2 's. On enlarging the platyrrhine expression data, we find Aotus ␥ is embryonic, Alouatta ␥ is inactive at term, and in Callithrix, ␥ 1 is down-regulated fetally, whereas ␥ 2 is up-regulated. Of eight mammalian taxa now represented per taxon by embryonic, fetal, and postnatal ␤-type globin gene expression data, four taxa are primates, and data for three of these primates are from this laboratory. Our results support a model in which a short distance (<10 kb) between and the adjacent ␥ is a plesiomorphic character that allows the LCR to drive embryonic expression of both genes, whereas a longer distance (>10 kb) impedes embryonic activation of the downstream gene.embryonic activation ͉ gene duplication ͉ gene expression ͉ hemoglobin