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Distinctive patterns of evolution of the δ-globin gene (HBD) in primates.

Moleirinho A, Lopes AM, Seixas S, Morales-Hojas R, Prata MJ, Amorim A - PLoS ONE (2015)

Bottom Line: We further show that not only the mode but also the rate of evolution of the δ-globin gene in higher primates are strictly associated with the fetal/adult β-cluster developmental switch.Although our results indicate that HBD might have experienced different selective pressures throughout primate evolution, as shown by different ω values between apes and Old World Monkeys + New World Monkeys (0.06 versus 0.43, respectively), these estimates corroborated a constrained evolution for HBD in Anthropoid lineages, which is unlikely to be related to protein function.Collectively, these findings suggest that sequence change at the δ-globin gene has been under strong selective constraints over 65 Myr of primate evolution, likely due to a regulatory role in ontogenic switches of gene expression.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal; Department of Biology, Faculty of Sciences, University of Porto, Porto, Portugal.

ABSTRACT
In most vertebrates, hemoglobin (Hb) is a heterotetramer composed of two dissimilar globin chains, which change during development according to the patterns of expression of α- and β-globin family members. In placental mammals, the β-globin cluster includes three early-expressed genes, ε(HBE)-γ(HBG)-ψβ(HBBP1), and the late expressed genes, δ (HBD) and β (HBB). While HBB encodes the major adult β-globin chain, HBD is weakly expressed or totally silent. Paradoxically, in human populations HBD shows high levels of conservation typical of genes under strong evolutionary constraints, possibly due to a regulatory role in the fetal-to-adult switch unique of Anthropoid primates. In this study, we have performed a comprehensive phylogenetic and comparative analysis of the two adult β-like globin genes in a set of diverse mammalian taxa, focusing on the evolution and functional divergence of HBD in primates. Our analysis revealed that anthropoids are an exception to a general pattern of concerted evolution in placental mammals, showing a high level of sequence conservation at HBD, less frequent and shorter gene conversion events. Moreover, this lineage is unique in the retention of a functional GATA-1 motif, known to be involved in the control of the developmental expression of the β-like globin genes. We further show that not only the mode but also the rate of evolution of the δ-globin gene in higher primates are strictly associated with the fetal/adult β-cluster developmental switch. To gain further insight into the possible functional constraints that have been shaping the evolutionary history of HBD in primates, we calculated dN/dS (ω) ratios under alternative models of gene evolution. Although our results indicate that HBD might have experienced different selective pressures throughout primate evolution, as shown by different ω values between apes and Old World Monkeys + New World Monkeys (0.06 versus 0.43, respectively), these estimates corroborated a constrained evolution for HBD in Anthropoid lineages, which is unlikely to be related to protein function. Collectively, these findings suggest that sequence change at the δ-globin gene has been under strong selective constraints over 65 Myr of primate evolution, likely due to a regulatory role in ontogenic switches of gene expression.

No MeSH data available.


Related in: MedlinePlus

Genetic distance vs divergence times between human and different primate species (Anthropoids and Prosimians) for β-like genes.Circles and dotted lines correspond to introns while diamonds and solid lines correspond to exons. Divergence times between humans and other species were obtained with TimeTree [32] and are as follows: Ptr: 6,3 Myr; Ggo 8,8 Myr; Ppy: 15.7 Myr; Nle 20,4 Myr; OWM (Mcc, Panu, Cgue and Caa): 29 Myr; NWM (Sbol, Cjac and Anan): 42,6 Myr; Tsyr: 65,5 Myr; Ogar: 74 Myr. Linear regression trend lines were set to intercept the origin.
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pone.0123365.g002: Genetic distance vs divergence times between human and different primate species (Anthropoids and Prosimians) for β-like genes.Circles and dotted lines correspond to introns while diamonds and solid lines correspond to exons. Divergence times between humans and other species were obtained with TimeTree [32] and are as follows: Ptr: 6,3 Myr; Ggo 8,8 Myr; Ppy: 15.7 Myr; Nle 20,4 Myr; OWM (Mcc, Panu, Cgue and Caa): 29 Myr; NWM (Sbol, Cjac and Anan): 42,6 Myr; Tsyr: 65,5 Myr; Ogar: 74 Myr. Linear regression trend lines were set to intercept the origin.

Mentions: From our previous analysis, it is apparent that while HBD has diverged at markedly different rates in different primate lineages, as shown by the variable branch lengths in the phylogenetic trees (Fig 1), anthropoid HBDs share a high sequence identity not only in their coding region but also at the promoter. As a first measure of the rate of HBD evolution, we compared the genetic distance between humans and 13 other primate species, for both adult β-like globin genes. HBBP1 was also included in the analysis due to the unusually slow substitution rates previously reported for this pseudogene estimated by comparison of human, gorilla and chimpanzee sequences [13]. Genetic distances were then plotted against the corresponding divergence times for each pairwise comparison, and the linear regression trend line was estimated for each group, as shown in Fig 2.


Distinctive patterns of evolution of the δ-globin gene (HBD) in primates.

Moleirinho A, Lopes AM, Seixas S, Morales-Hojas R, Prata MJ, Amorim A - PLoS ONE (2015)

Genetic distance vs divergence times between human and different primate species (Anthropoids and Prosimians) for β-like genes.Circles and dotted lines correspond to introns while diamonds and solid lines correspond to exons. Divergence times between humans and other species were obtained with TimeTree [32] and are as follows: Ptr: 6,3 Myr; Ggo 8,8 Myr; Ppy: 15.7 Myr; Nle 20,4 Myr; OWM (Mcc, Panu, Cgue and Caa): 29 Myr; NWM (Sbol, Cjac and Anan): 42,6 Myr; Tsyr: 65,5 Myr; Ogar: 74 Myr. Linear regression trend lines were set to intercept the origin.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390247&req=5

pone.0123365.g002: Genetic distance vs divergence times between human and different primate species (Anthropoids and Prosimians) for β-like genes.Circles and dotted lines correspond to introns while diamonds and solid lines correspond to exons. Divergence times between humans and other species were obtained with TimeTree [32] and are as follows: Ptr: 6,3 Myr; Ggo 8,8 Myr; Ppy: 15.7 Myr; Nle 20,4 Myr; OWM (Mcc, Panu, Cgue and Caa): 29 Myr; NWM (Sbol, Cjac and Anan): 42,6 Myr; Tsyr: 65,5 Myr; Ogar: 74 Myr. Linear regression trend lines were set to intercept the origin.
Mentions: From our previous analysis, it is apparent that while HBD has diverged at markedly different rates in different primate lineages, as shown by the variable branch lengths in the phylogenetic trees (Fig 1), anthropoid HBDs share a high sequence identity not only in their coding region but also at the promoter. As a first measure of the rate of HBD evolution, we compared the genetic distance between humans and 13 other primate species, for both adult β-like globin genes. HBBP1 was also included in the analysis due to the unusually slow substitution rates previously reported for this pseudogene estimated by comparison of human, gorilla and chimpanzee sequences [13]. Genetic distances were then plotted against the corresponding divergence times for each pairwise comparison, and the linear regression trend line was estimated for each group, as shown in Fig 2.

Bottom Line: We further show that not only the mode but also the rate of evolution of the δ-globin gene in higher primates are strictly associated with the fetal/adult β-cluster developmental switch.Although our results indicate that HBD might have experienced different selective pressures throughout primate evolution, as shown by different ω values between apes and Old World Monkeys + New World Monkeys (0.06 versus 0.43, respectively), these estimates corroborated a constrained evolution for HBD in Anthropoid lineages, which is unlikely to be related to protein function.Collectively, these findings suggest that sequence change at the δ-globin gene has been under strong selective constraints over 65 Myr of primate evolution, likely due to a regulatory role in ontogenic switches of gene expression.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal; Department of Biology, Faculty of Sciences, University of Porto, Porto, Portugal.

ABSTRACT
In most vertebrates, hemoglobin (Hb) is a heterotetramer composed of two dissimilar globin chains, which change during development according to the patterns of expression of α- and β-globin family members. In placental mammals, the β-globin cluster includes three early-expressed genes, ε(HBE)-γ(HBG)-ψβ(HBBP1), and the late expressed genes, δ (HBD) and β (HBB). While HBB encodes the major adult β-globin chain, HBD is weakly expressed or totally silent. Paradoxically, in human populations HBD shows high levels of conservation typical of genes under strong evolutionary constraints, possibly due to a regulatory role in the fetal-to-adult switch unique of Anthropoid primates. In this study, we have performed a comprehensive phylogenetic and comparative analysis of the two adult β-like globin genes in a set of diverse mammalian taxa, focusing on the evolution and functional divergence of HBD in primates. Our analysis revealed that anthropoids are an exception to a general pattern of concerted evolution in placental mammals, showing a high level of sequence conservation at HBD, less frequent and shorter gene conversion events. Moreover, this lineage is unique in the retention of a functional GATA-1 motif, known to be involved in the control of the developmental expression of the β-like globin genes. We further show that not only the mode but also the rate of evolution of the δ-globin gene in higher primates are strictly associated with the fetal/adult β-cluster developmental switch. To gain further insight into the possible functional constraints that have been shaping the evolutionary history of HBD in primates, we calculated dN/dS (ω) ratios under alternative models of gene evolution. Although our results indicate that HBD might have experienced different selective pressures throughout primate evolution, as shown by different ω values between apes and Old World Monkeys + New World Monkeys (0.06 versus 0.43, respectively), these estimates corroborated a constrained evolution for HBD in Anthropoid lineages, which is unlikely to be related to protein function. Collectively, these findings suggest that sequence change at the δ-globin gene has been under strong selective constraints over 65 Myr of primate evolution, likely due to a regulatory role in ontogenic switches of gene expression.

No MeSH data available.


Related in: MedlinePlus