ABSTRACT
PURPOSE: In the past, a role of thyroid hormones in human evolution has been hypothesized. T3, the metabolically active form, derives from extrathyroidal conversion of T4 by deionidase 2 (D2) enzyme encoded by DIO2 gene. In thyroid-deficient patients, decreased levels of free T3 have been associated with the polymorphism rs225014 A/G in DIO2, which causes the substitution of Threonine with Alanine (p.Thr92Ala) at protein level. METHODS: We compared DNA and protein sequences of D2 from archaic human subspecies with those of contemporary humans. RESULTS: Neanderthals and Denisovans displayed only the G allele at the rs225014 polymorphism, which encodes for an Alanine on the amino acid level. These data suggest that these hominines were homozygous for the Ala amino acid. These arcaic humans often lived in condition of iodine deficiency and thus, defective mechanisms of T3 biosynthesis could be life threatining. A reduced D2 activity is likely to cause decreased T3 levels, which could be critical for those individuals. Neanderthals and Denisovans were hunters/gatherers, and their diet was mainly based on the consumption of meat, with a low intake of carbohydrates. The need for circulating T3 is reduced at such alimentary conditions. On the basis of our genome comparisons the A allele, corresponding to Threonine and associated with higher levels of circulating T3 in thyroid-deficient patients, appeared for the first time during evolution in Anatomically Modern Humans during the Upper Pleistocene and has been conserved during the Neolithic age. With the advent of agriculture and herding, individuals carrying A allele might have a higher probability for surviving and reproducing. Thus, the variant was positively selected during the evolution. CONCLUSION: Here we present an evolutionary perspective for p.Thr92Ala variant of D2 from Neanderthals to Anatomically Modern Humans.
Subject(s)
Evolution, Molecular , Iodide Peroxidase/genetics , Polymorphism, Single Nucleotide , Alanine/genetics , Alleles , Amino Acid Substitution/genetics , Animals , Gene Frequency , Genetics, Population , Geography , History, Ancient , Humans , Neanderthals/genetics , Threonine/genetics , Iodothyronine Deiodinase Type IISubject(s)
Cytoskeletal Proteins/genetics , Growth Disorders/diagnosis , Growth Disorders/genetics , Intellectual Disability/diagnosis , Intellectual Disability/genetics , Microcephaly/diagnosis , Microcephaly/genetics , Syndactyly/diagnosis , Syndactyly/genetics , Facies , Growth Disorders/physiopathology , Humans , Infant , Intellectual Disability/physiopathology , Male , Microcephaly/physiopathology , Mutation , Syndactyly/physiopathologyABSTRACT
Rigorous methods for the post-HF (HF-Hartree-Fock) determination of correlation corrections for crystalline solids are currently being developed following different strategies. The CRYSTAL program developed in Torino and Daresbury provides accurate HF solutions for periodic systems in a basis set of Gaussian type functions; for insulators, the occupied HF manifold can be represented as an antisymmetrized product of well localized Wannier functions. This makes possible the extension to nonconducting crystals of local correlation linear scaling On techniques as successfully and efficiently implemented in Stuttgart's MOLPRO program. These methods exploit the fact that dynamic electron correlation effects between remote parts of a molecule (manifesting as dispersive interactions in intermolecular perturbation theory) decay as an inverse sixth power of the distance R between these fragments, that is, much more quickly than the Coulomb interactions that are treated already at the HF level. Translational symmetry then permits the crystalline problem to be reduced to one concerning a cluster around the reference zero cell. A periodic local correlation program (CRYSCOR) has been prepared along these lines, limited for the moment to the solution of second-order Moller-Plesset equations. Exploitation of point group symmetry is shown to be more important and useful than in the molecular case. The computational strategy adopted and preliminary results concerning five semiconductors with tetrahedral structure (C, Si, SiC, BN, and BeS) are presented and discussed.
ABSTRACT
To assess the relative reactivity of the spin-orbit excited state of atomic Cl with molecular hydrogen, we have measured differential cross sections using an atomic Cl beam with a known concentration of the ground and excited spin-orbit states. These are compared with the first determination of the cross sections from quantum mechanical scattering calculations on a set of coupled ab initio potential energy surfaces. The comparison suggests that these surfaces may underestimate the degree of rotational excitation of the HCl products and that the excited spin-orbit state plays a minor role in the reaction.
