Study on Molecular Mechanism of Hemoglobin Adaptability of Thermophis bai-leyi to High Altitude Hypoxia
In this study,genomics,molecular evolution,and computational biology were combined to investigate the molecular mechanisms of hemoglobin(Hb)gene family members,gene cluster structure,and protein structure in the adaptation of Thermophis baileyi to the hypoxic environment on the plateau.The results showed that the genome of T.baileyi contains two α globin genes and twoβ globin genes,among which the β globin gene cluster was highly conserved.αA globin gene underwent a gene translocation event during the differentiation and formation of snakes and lizards in the ancestral squamates,and the post-translocation arrangement pattern in snakes is(5'-RREB1,SSR1,αA,RIOK1,DSP-3').There were two and four potential positive selection sites in the αD and β2 genes of the T.baileyi,respectively,where mutations at the αD subunit p.Arg9Lys and p.Val36Thr positions resulted in an increase in the size and hydrophilicity of the heme pocket,and this mutation was beneficial for improving the O2 transport efficiency.β2 subunit p.Ser53Asn mutations result in an increase in the hydrophilicity of the heme pocket of this subunit.The β2 subunit p.Ile112Leu,p.Thr135Cys and p.Ala139Ser mutations led to increase internal stability of the β2 subunit,which facilitated the accumulation of the corresponding Hb isoforms in erythrocytes.In addition,compared with Thamnophis sirtalis,there was a significant reduction in the number of salt bridges and hydrogen bonds between αβ/αβ of T.baileyi(αDβ2)2 isoforms,which would make the transition process of T-R state easier to occur.In conclusion,the changes in protein conformation and physicochemical properties caused by positive selection mutations in the αD and β2 genes of T.baileyi may lead to an increase in the oxygen affinity of the corresponding of Hb isoforms,thereby improving the efficiency of oxygen transport under extreme hypoxic conditions.
Thermophis baileyiHemoglobinMolecular evolutionProtein structureAdaptability to high altitude hypoxia
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