Evidence map›Paper›PMID 32436183›Full record

ArticleJournal of endocrinological investigation2020

Thr92Ala polymorphism in the type 2 deiodinase gene: an evolutionary perspective.

C Ricci, K R Kakularam, C Marzocchi, G Capecchi, G Riolo, F Boschin, H Kuhn, M G Castagna, S Cantara

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In one paragraph

Article in Journal of endocrinological investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.0field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 12 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

C RicciDepartment of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 16, 53100, Siena, Italy.
K R KakularamCorporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Institute of Biochemistry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
C MarzocchiDepartment of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 16, 53100, Siena, Italy.
G CapecchiDepartment of Physical Sciences, Earth and Environment, University of Siena, Siena, Italy.
G RioloDepartment of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 16, 53100, Siena, Italy.
F BoschinDepartment of Physical Sciences, Earth and Environment, University of Siena, Siena, Italy.
H KuhnCorporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Institute of Biochemistry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
M G CastagnaDepartment of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 16, 53100, Siena, Italy.
S CantaraDepartment of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 16, 53100, Siena, Italy. cantara@unisi.it.ORCID http://orcid.org/0000-0002-5741-295X
University of Siena · ITFreie Universität Berlin · DE

Funding

German Research Council KU 961-14/1
6 · The paper itself

Abstract

purposeIn 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.

methodsWe compared DNA and protein sequences of D2 from archaic human subspecies with those of contemporary humans.

resultsNeanderthals 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.

conclusionHere we present an evolutionary perspective for p.Thr92Ala variant of D2 from Neanderthals to Anatomically Modern Humans.

Indexed as

Evolution, MolecularPolymorphism, Single NucleotideAlanineAllelesAmino Acid SubstitutionAnimalsGene FrequencyGenetics, PopulationGeographyHistory, AncientHumansIodide PeroxidaseIodothyronine Deiodinase Type IINeanderthalsThreonineAlanineIodide PeroxidaseIodothyronine Deiodinase Type IIThreonineDeionidase type 2DenisovansNeanderthalsrs225014T3 levelUpper paleolithic

Identifiers

PMID32436183
OpenAlexW3027750559

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.