Evolution of Hemoglobin and Its Genes

Abstract

Insights into the evolution of hemoglobins and their genes are an abundant source of ideas about hemoglobin function and regulation of globin gene expression. This chapter presents the multiple genes and gene families encoding human globins, summarizes major events in the evolution of the hemoglobin gene clusters, and discusses how these studies provide insights into regulation of globin genes. While the genes in and around the alpha-like globin gene complex are relatively stable, the beta-like globin gene clusters are more dynamic, showing evidence of transposition to a new locus and frequent lineage-specific expansions and deletions. The cis-regulatory modules controlling levels and timing of gene expression are a mix of conserved and lineage-specific DNA, perhaps reflecting evolutionary constraint on core regulatory functions shared broadly in mammals and adaptive fine-tuning in different orders of mammals.

Global transcriptome analyses of human and murine terminal erythroid differentiation

“…This conclusion has been supported on a limited basis by gene expression analyses of varying populations of murine and human erythroid cells. 8,[27][28][29][30][31][32][33][34][35] Our transcriptome data strengthen these observations regarding the stage-specific complexity of erythroid differentiation.…”

“…For instance, variation in glucose utilization, vitamin C metabolism, regulation of ion content and cell size, membrane protein composition and properties, and mechanisms of stress erythropoiesis are known differences between human and murine erythroid cells. 30,[64][65][66][67][68][69][70] Other differences include patterns of gene regulation (eg, the well-known dissimilarities in globin gene regulation) and differences in transcript isoform composition generated by alternate splicing, such as the differences in exon composition of the ALAS2 complementary DNA isoforms between mouse and man. 71,72 One striking observation from our analyses was, in contrast to human, there was a near-global decrease in gene expression during murine terminal erythroid differentiation.…”

Analysis of Bone Mineral Density according to Hemoglobin in University Students

“…Hb consists of globin molecules and these proteins, in turn, are folded chains of a large number of different amino acids called polypeptides. There is more than one hemoglobin gene: in humans, hemoglobin A is coded for by the genes, HbA1, HbA2, and HbB [6]. Anemia is usually defined as a decrease in the amount of red blood cells or hemoglobin in the blood.…”

Transcriptional Mechanisms Underlying Hemoglobin Synthesis

“…Other articles in this collection have highlighted the molecular biology of genes encoding hemoglobin subunits (Hardison 2012), hemoglobinopathies (Nienhuis and Nathan 2012;Higgs 2013), and human genetic studies that revealed an extremely important new regulator of hemoglobin switching, the transcriptional coregulator BCL11A (Lettre 2012;Sankaran and Orkin 2013). Undoubtedly, BCL11A is a crucial component of the hemoglobin switching machinery, and major efforts are under way to elucidate how BCL11A functions in physiological and pathological contexts.…”