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Ecological Genetics of Thyroid Hormone Physiology in Humans and Wild Animals

Written By

Asano Ishikawa and Jun Kitano

Submitted: 20 November 2011 Published: 18 July 2012

DOI: 10.5772/45969

From the Edited Volume

Thyroid Hormone

Edited by Neeraj Kumar Agrawal

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1. Introduction

Hormones are important mediators in the responses of a suite of phenotypic traits to environmental changes. Therefore, populations inhabiting different environments are expected to vary in several hormonal pathways. Such variation results from both plastic response to environments and genetic differences. Therefore, information about the genetic basis of hormonal variation is crucial to better understand the ecological and evolutionary mechanisms of phenotypic diversification in animals. Furthermore, information about the racial and geographical variation in hormone physiology is crucial for better diagnosis of hormone-related diseases in clinical fields. Thyroid hormones play key roles in regulation of many physiological and behavioral traits, such as metabolism, ion homeostasis, basal activity, and longevity. Therefore, thyroid hormone can play important roles in adaptation to external environments. In the present study, we review interspecies, racial, geographical, and interindividual variation in the thyroid hormone pathways in humans and other animals. The present review focuses on natural and subclinical variation in thyroid hormone physiology and will not cover the genetic basis for congenital hypothyroidism [1,2,3,4,5], congenital hyperthyroidism [6,7], autoimmune diseases [8], and thyroid cancers [9], for which a number of good review articles are already available. We also review what is known about the genetic basis for such variation. We found several shared features in the patterns of variation in thyroid hormone physiology in humans and other animals. This review demonstrates the importance of undertaking further integrative studies of human genetics and animal ecology for a better understanding of the ecological and genetic mechanisms of variation in thyroid hormone signaling pathways.

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2. Variation in thyroid hormone physiology in humans

2.1. Interindividual, geographical, and racial variation

Geographical variation in the frequency of euthyroid endemic goiter has been extensively investigated [10,11,12]. In addition to iodine deficiency, other factors, such as smoking, age, sex, goitrogens, and body mass index, can also influence the etiology of euthyroid endemic goiter [13]. Although genetic predisposition to euthyroid goiter has been demonstrated [12,13,14], the molecular genetic mechanisms underlying the variation in susceptibility to goiter are not well understood. Polymorphism at the thyroglobulin (TG) [15,16] and Na+/I symporter (NIS) loci [17] are reportedly associated with euthyroid goiter; however, linkage mapping in different families could not connect euthyroid goiter with such genetic variation [18,19].

Racial variation in the level of thyroid-stimulating hormone (TSH), one of the major hormones regulating synthesis and secretion of thyroid hormone, has been also found. Multiple studies have revealed that serum TSH levels are higher in whites and Mexican Americans than in blacks [20,21,22]. These results suggest that race-specific reference values of TSH are necessary for evaluation of thyroid hormone-related diseases. Currently, the genetic and ecological basis for the racial variation in TSH levels is not well understood. The serum levels of thyroxine-binding globulin (TBG), a major thyroid hormone-binding protein in plasma, are lower in Australian Aborigines than in Caucasians in Western Australia [23]. Aborigines have a TBG variant that has reduced affinity for thyroid hormone and is more susceptible to heat and acid denaturation [24,25,26]. Two amino acids are substituted in this variant, one of which is considered responsible for the low binding affinity for thyroid hormones [26]. Aborigines usually have lower T4 levels, but have normal TSH levels and normal or borderline T3 levels. Because Aborigines do not show any clinical symptoms of hypothyroidism, the homeostasis of thyroid hormone physiology in Aborigines differs from that in other human populations.

Although the adaptive significance of the variations remain elusive in the above cases, some interpopulation variation may result from adaptive evolution to divergent environments. Serum free T4 levels are higher in indigenous Evenki women than in nonindigenous Russian women living in the same communities in central Siberia [27]. The variation in free T4 levels was correlated with the variation in basal metabolic rate both in Evenki and Russian men and women [27]. Similar cases were also found for indigenous Nenets and nonindigenous Russians: both showed significant increases in total T4 levels during winter, but the magnitude of the increase was significantly greater in the Nenets than in the Russians [27]. Because thyroid hormones play important roles in regulating metabolic rate and adaptation to cold environments [28,29], human populations inhabiting colder environments may acquire genetic basis for more efficient thyroid hormone-induced thermogenesis and may therefore be genetically adapted to cold environments [30].

Interindividual differences in TSH levels are prevalent, and have been found to be associated with variation in life span. In Ashkenazi Jews and Northern Italians, healthy oldest-old people of around 100 years of age had higher TSH levels than elderly controls of around 70 years of age [31,32]. In addition, follow-up studies revealed that participants with abnormally high TSH levels had a lower mortality rate than those with normal or low TSH levels [33]. The offspring of Ashkenazi Jewish centenarians had significantly higher TSH levels, suggesting that higher TSH levels and longevity have heritable components [32]; however, the molecular mechanisms of this variation are unknown.

2.2. Genetic basis for variation

In addition to the case of TGB in Australian Aborigines [34], polymorphisms associated with variation in thyroid hormone physiology have been found in other populations [35]. Several studies have focused on candidate genes involved in thyroid hormone signaling pathways and revealed that single nucleotide polymorphisms (SNPs) of the TSH receptor (TSHR) [36], iodothyronine deiodinases (DIO1, DIO2, and DIO3) [36,37], thyroid hormone transporter and thyroid hormone receptor genes accounted for variation in serum TSH and thyroid hormone levels [38,39]. Genome-wide association studies have also identified several genes involved in thyroid hormone signaling. Three SNPs at intron 1 of the phosphodiesterase 8B (PDE8B) gene are significantly associated with serum TSH levels [40,41]. PDE8B encodes a high-affinity cAMP-specific phosphodiesterase catalyzing the hydrolysis and inactivation of cAMP. Because the PDE8B transcript is undetectable in the pituitary, it is thought that PDE8B may affect TSH levels through its effect on TSH-dependent thyroid hormone synthesis and secretion in the thyroid gland. Interestingly, other cAMP-specific phosphodiesterases have also been showed to be associated with variation in TSH levels [41]. Since there are only a few studies revealing the mechanisms by which SNPs modify thyroid hormone signaling [38], further studies are needed to confirm their actual contribution to the natural variation in thyroid hormone physiology.

If genes involved in thyroid hormone pathways were targets of natural selection, we would be able to find some signatures of natural selection in the human genome. When natural selection increases the frequency of a new beneficial mutation in a population, the neighboring regions will reduce the genetic variation and increase the level of linkage disequilibrium [42]. Two genes involved in the thyroid hormone pathway, thyroid hormone receptor interactor 4 (TRIP4) and iodotyrosine deiodinase (IYD), showed a signature of selection in the genome of African Pygmies [43]. Importantly, a low frequency (9.4%) of goiter was reported for an African Pygmy population, although they inhabit an iodine-deficient region [44]. Because another population in the same region had a much higher frequency of goiter (42.9%), López Herráez et al. (2010) concluded that the signatures of selection in these genes might reflect genetic adaptations of Pygmies to iodine-deficient diets. Another study tried to identify the genes whose allele frequencies were significantly correlated with climate. The frequency of an SNP in TRIP6 showed strong correlation with latitude [45].

The high rate of nonsynonymous (amino acid–altering) changes compared with the rate of synonymous (silent) changes also indicates that the genes might be under positive selection [42]. By comparing the synonymous and nonsynonymous substitutions in the human and chimp genomes, putatively positively selected genes were screened [46]. Genes expressed in the thyroid gland have an excess of rapidly evolving genes compared with other tissues, except testis, which has more putatively positively selected genes [46]. Changes in thyroid hormone physiology may contribute to some of the physiological and morphological divergence between humans and apes [47,48].

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3. Inter-population and geographical variation in thyroid hormone physiology in animals

Anatomical studies conducted in the 1960s and 1970s showed interspecies morphological variation for fishes and amphibians [49,50]. Since then, natural variation in thyroid hormone physiology has been extensively investigated in diverse taxa of vertebrate (Table 1). Some of the variation results from environmental factors. For example, environmental contaminants can cause goiter. In salmon populations introduced into the Great Lakes in the late 1960s, the frequency of thyroid goiter increased in the mid-1970s [51,52,53]. In addition, herring gulls Larus argentatus from the Great Lakes also suffered from goiter in the 1980s [54]. It was demonstrated that laboratory rats fed with the salmons caught in the lakes exhibited hypothyroidism and goiter, suggesting the presence of goitrogenic substances in the Great Lakes fishes [55].

Species/FamilyPhenotypic variationPotential factors and functionsReference
Intraspecific variation
Coho salmon Goiter, T4, T3Goitrogen[51,53,97]
Chinook salmon GoiterGoitrogen[53]
Herring gullGoiterGoitrogen[54]
American alligatorT4Goitrogen[98]
Japanese pond frogMorphology[49]
Bottlenose dolphin T4 and T3Temperature[62]
Northern cardinalT4 and T3[61]
Alaskan husky T4 and T3Temperature[60]
Bonnethead sharkT4 and T3 in yolkTemperature[70]
Brook charr T4 and T3Migration[87]
Stickleback Goiter, TSHß, T4,T3Migration, metabolism[57,58,86]
Interspecific variation
PoeciliidaeMorphology, tumor[50,99,100]
Spadefoot toadT4, T3, sensitivityDry environment, metamorphosis[63]
Big-eared mouseT4, T3, iodideLow iodide concentration[59]
RodentT4Life span[101]

Table 1.

Variation in thyroid hormone physiology in natural animal populations

Goiters were also observed in hatchery fishes and possibly resulted from iodine deficiency, because iodine treatment was able to cure the goiter [56]. In the case of the threespine stickleback Gasterosteus aculeatus, interpopulation variation in susceptibility to goiter when reared in fresh water was observed [57,58], although whether the goiter in the sticklebacks was caused by iodine deficiency is unknown. Interestingly, a mammalian species, Auliscomys boliviensis, inhabiting an environment severely depleted of iodine did not show goiter [59], suggesting that genetic variation in the susceptibility to endemic goiter exists among populations and species.

Latitudinal variation in plasma concentrations of thyroid hormone has been observed in both mammals and birds, and these variations might have evolved as adaptations to environments with divergent temperatures. Plasma total T4, free T4, and total T3 levels of sled dogs living in Alaska were higher than dogs in New York, especially in winter [60]. In addition, plasma T3 increased with increasing latitude in the northern cardinals Cardinalis cardinalis, whereas plasma T4 did not show a simple latitudinal cline: both southern and northern birds had higher T4 levels than birds living at an intermediate latitude [61]. In mammals, bottlenose dolphins Tursiops truncatus show variation in thyroid hormone concentrations between populations inhabiting different latitudes [62]: plasma total T3 and T4 were higher in dolphins from South Carolina with colder year-round temperatures than those from Florida with much warmer water temperatures. Since thyroid hormones play key roles in metabolism and heat generation, evolutionary adaptation to habitats with different temperatures may account for some of the latitudinal and geographical variation in thyroid hormone levels among natural populations. The genetic basis for the latitudinal variation is currently unknown.

Several studies have demonstrated that variation in thyroid hormone physiology correlates with other potentially adaptive traits. Interspecies variation in tissue thyroid hormone levels and tissue sensitivity to thyroid hormone may be correlated with variation in the duration of the larval period in spadefoot toads [63]. For example, the tadpole of the desert-dwelling toad Scaphiopus couchii has higher tail and liver levels of thyroid hormone, and the tail tip is more sensitive to thyroid hormone in vitro than tail tips of other closely related species [63]. Because frog metamorphosis is controlled by thyroid hormone, the higher thyroid hormone levels and the higher sensitivity may explain the short larval period in this species. Rapid metamorphosis (i.e., the short period of water-dwelling at the tadpole stage) observed in the desert toad is likely adaptive for survival in the deserts where water is scarce [64,65].

Thyroid hormones also play critical roles as yolk hormones in mammalian [66], bird [67], and teleost [68,69] development. In the bonnethead shark Sphyrna tiburo, the concentrations of T3 and T4 in the yolk from the Tampa Bay population were consistently higher than those in the yolk from the Florida Bay population [70]. The bonnethead shark in Tampa Bay develops faster and is larger at birth than that in Florida Bay [71]. Tampa Bay is located in a more northern region and is colder than Florida Bay. Because rapid growth is generally adaptive in colder environments [72,73], higher york thyroid hormone levels in the Tampa Bay population may be adaptive.

Thyroid hormone is also implicated in the regulation of longevity in animals [74,75]. Long-lived species of squirrels, deer mice, bats and mole-rats maintain low levels of thyroid hormone [76,77,78,79]. Hypothyroid Wister rats live longer than hyperthyroid rats [80]. Furthermore, investigations in the Ames and Snell dwarf mice have demonstrated that mutation at the Prop-1 and Pit-1 genes lead to defects in the generation of pituitary cells including thyrotrope and the dwarf mice have extended longevity [81,82,83,84,85]. Thus, it is possible that changes in the thyroid hormone pathway are involved in variation of life span among wild animals, as is observed among human races (see above). Further research on the genetic basis for the low thyroid hormone levels observed in the long-lived animals should be conducted.

Divergence in thyroid hormone physiology may also be important for adaptation of stickleback fishes to marine and freshwater environments [86]. Stream-resident populations of the threespine stickleback have repeatedly evolved from ancestral marine populations. First, Kitano et al. (2010) found plasma thyroid hormone levels and metabolic rate were lower in stream-resident populations than in ancestral marine populations [86]. Since thyroid hormones regulate metabolic rate in sticklebacks [86], it is likely that lower thyroid hormone in stream-resident sticklebacks is adaptive for permanent residency in small streams where oxygen and food are often scarce. In addition, the expression level of thyroid stimulating hormone TSHß2 gene was significantly lower in the pituitary gland of stream-resident fish than in that of marine fish. Allele-specific expression analysis with F1 hybrids revealed that some of the differences in TSHß2 expression levels were caused by cis-regulatory changes at the TSHß2 locus. Importantly, a signature of natural selection was found at TSHß2 locus: several SNPs within the cis-regulatory region exhibited marked differences in the allele frequency between marine and stream-resident populations. Thus, changes in the thyroid hormone pathways may play important roles in genetic adaptation to freshwater environments. In other fishes exhibiting alternate life history style, such as the brook charr Salvelinus fontinalis anadromous and resident forms show differences in thyroid hormone concentrations, although genetic factors seem to be of little importance in the interpopulation variation seen in the brook charr [87].

Other than the TSH loci in sticklebacks, there are few studies that have examined whether thyroid hormone-related genes are under selective pressure in wild animal populations. However, domestication seems to be a strong artificial selection on thyroid hormone-related genes. Very strong selective sweeps were found at the TSHR loci in chickens [88] and sheep [89]. Because TSH is found to regulate photoperiodic control of reproduction [90,91,92,93,94], artificial selection favoring continuous reproduction under domestication might act on the TSH locus.

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4. Conclusions and future directions

We found similar features in the patterns of variation in thyroid hormone physiology in humans and other animals. First, genetic variation in the susceptibility to endemic goiter exists among populations and species. Second, some of the latitudinal and racial variation in thyroid hormone physiology likely results from adaptation to environments with divergent ambient temperatures. Third, variation in thyroid hormone physiology may be associated with variation in longevity. Fourth, genomic scan of signatures of selection have revealed that some thyroid hormone-related genes experience selective pressure during evolution or domestication.

In humans, it is very difficult to experimentally test the adaptive significance of such variation. However, ecological experiments can be conducted using animals. For example, reciprocal transplant experiments on divergent populations or species with different thyroid hormone physiology can test whether wild animals have higher fitness in native habitats than in foreign habitats [95,96]. We can also investigate whether the fitness is correlated with the thyroid hormone levels. In addition, hormonal manipulation would be able to directly test whether the higher or lower thyroid hormone levels can change the fitness in a variety of environments.

Until recently, it has been difficult to study the genetic basis for physiological differences between natural animal populations. However, it is now becoming increasingly easier to conduct genomic studies because of the recent progress in genomic technologies. Therefore, we can test whether candidate loci involved in thyroid hormone signaling pathways are correlated with fitness in natural environments or laboratory conditions. Furthermore, ecological and genomic studies of wild animal populations will help answer fundamental evolutionary questions, such as whether the same environmental variables are strong agents of natural selection on the thyroid hormone pathways and whether genetic variation in the same genes caused the adaptive divergence in thyroid hormone physiology across diverse taxa, including humans.

Acknowledgement

This research is supported by JST PRESTO program, the Naito Foundation, Grant-in-Aid for Scientific Research on Innovative Areas (23113007 and 23113001) from the Ministry of Education, Science, Sports, and Culture to JK. AI is a Fellow of the Japan Society of Promotion of Science.

References

  1. 1. Park SM, Chatterjee VKK2005Genetics of congenital hypothyroidism. J Med Genet 42379389
  2. 2. GrasbergerH.RefetoffS.2011Genetic causes of congenital hypothyroidism due to dyshormonogenesis. Curr Opin Pediatr 23421428
  3. 3. Rastogi MV, LaFranchi SH2010Congenital hypothyroidism. Orphanet J Rare Dis 5: 17.
  4. 4. GrütersA.KrudeH.BiebermannH.2004Molecular genetic defects in congenital hypothyroidism. Eur J Endocrinol 151: U39U44.
  5. 5. MorenoJ. C.de VijlderJ. J. M.VulsmaT.Ris-StalpersC.2003Genetic basis of hypothyroidism: recent advances, gaps and strategies for future research. Trends Endocrinol Metab 14318326
  6. 6. HébrantA.van StaverenV. C. G.MaenhautC.DumontJ. E.LeclèreJ.2011Genetic hyperthyroidism: hyperthyroidism due to activating TSHR mutations. Eur J Endocrinol 16419
  7. 7. PrummelM. F.StriederT.WiersingaW. M.2004The environment and autoimmune thyroid diseases. Eur J Endocrinol 150605618
  8. 8. TomerY.2010Genetic susceptibility to autoimmune thyroid disease: past, present, and future. Thyroid 20715725
  9. 9. LandaI.RobledoM.2011Association studies in thyroid cancer susceptibility: are we on the right track? J Mol Endocrinol 47: R43R58
  10. 10. SelinusO.AllowayB.CentenoJ. A.FinkelmanR. B.FiugeR.et al.2005Essentials of Medical Geology. Burlington: Elsevier.
  11. 11. KoutrasD. A.MatovinovicJ.VoughtR.1985The ecology of iodine. In: Stanbury JB, Hetzel BS, editors. Endemic Goitre and Cretinism, Iodine Nutrition in Health and Disease. New York: Wiley. 185195
  12. 12. Davenport CB1932The genetical factor in endemic goiter. Lancaster: Lancaster Press.
  13. 13. BöttcherY.EszlingerM.TönjesA.PaschkeR.2005The genetics of euthyroid familial goiter. Trends Endocrinol Metab 16314319
  14. 14. SingerJ.EszlingerM.WichtJ.PaschkeR.2011Evidence for a more pronounced effect of genetic predisposition than environmental factors on goitrogenesis by a case control study in an area with low normal iodine supply. Horm Metab Res 43349354
  15. 15. Perez-CentenoC.Gonzalez-SarmientoR.MoriesM. T.CorralesJ. J.Miralles-GarciaJ. M.1996Thyroglobulin exon 10 gene point mutation in a patient with endemic goiter. Thyroid 6423427
  16. 16. CorralJ.MartinC.PérezR.SánchezI.González-SarmientoR.et al.1993Thyroglobulin gene point mutation associated with non-endemic simple goitre. Lancet 341462464
  17. 17. MatsudaA.KosugiS.1997A homozygous missense mutation of the sodium/iodide symporter gene causing iodide transport defect. J Clin Endocrinol Metab 8239663971
  18. 18. NeumannS.BayerY.ReskeA.TajtákováPaschke. R.2003Further indications for genetic heterogeneity of euthyroid familial goiter. J Mol Med 81736745
  19. 19. NeumannS.WillgerodtH.AckermannF.ReskeA.JungM.et al.1999Linkage of familial euthyroid goiter to the multinodular goiter-1 locus and exclusion of the candidate genes thyroglobulin, thyroperoxidase, and Na+/I− symporter. J Clin Endocrinol Metab 8437503756
  20. 20. Hollowell JG, Staehling CA, Flanders WD, Hannon WH, Gunter EW, et al.2002Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 87489499
  21. 21. Walker JA, Illions EH, Huddleston JF, Smallridge RC2005Racial comparisons of thyroid function and autoimmunity during pregnancy and the postpartum period. Obstet Gynecol 10613651371
  22. 22. SurksM. I.BoucaiL.2010Age- and race-based serum thyrotropin reference limits. J Clin Endocrinol Metab 95496502
  23. 23. DickM.WatsonF.1980Prevalent low serum thyroxine-binding globulin level in western Australian Aborigines. Med J Australia 1115118
  24. 24. DickM.WatsonF.1981A possible variant of thyroxine-binding globulin in Australian Aborigines. Clin Chim Acta 116361367
  25. 25. TakedaK.MoriY.SobieszczykS.SeoH.DickM.et al.1989Sequence of the variant thyroxine-binding globulin of Australian aborigines. Only one of two amino acid replacements is responsible for its altered properties. J Clin Invest 8313441348
  26. 26. MurataY.RefetoffS.SarneD. H.DickM.WatsonF.1985Variant thyroxine-binding globulin in serum of Australian aborigines: its physical, chemical and biological properties. J Endocrinol Invest 8225232
  27. 27. Leonard WR, Sorensen MV, Galloway VA, Spencer GJ, Mosher MJ, et al.2002Climatic influences on basal metabolic rates among circumpolar populations. Am J Hum Biol 14609620
  28. 28. LaurbergP.AndersenS.KarmisholtJ.2005Cold adaptation and thyroid hormone metabolism. Thieme eJournal 37545549
  29. 29. Launay-CJ.SavoureyG.2009Cold adaptations. Ind Health 47221227
  30. 30. Leonard WR, Snodgrass JJ, Sorensen MV2005Metaolic adaptation in indigenous Siberian populations. Ann Rev Anthropol 34451471
  31. 31. RavagliaG.FortiP.MaioliF.NesiB.PratelliL.et al.2000Blood micronutrient and thyroid hormone concentrations in the oldest-old. J Clin Endocrinol Metab 8522602265
  32. 32. AtzmonG.BarzilaiN.HollowellJ. G.SurksM. I.GabrielyI.2009Extreme longevity is associated with increased serum thyrotropin. J Clin Endocrinol Metab 9412511254
  33. 33. GusseklooJ.van ExelE.de CraenA. J.MeindersA. E.FrolichM.et al.2004Thyroid status, disability and cognitive function, and survival in old age. JAMA- J Am Med Assoc 29225912599
  34. 34. MurataY.RefetofS.SameD. H.DickM.WatsonF.Variantthyroxine-binding.globulinin.serumof.AustralianAborigines-its.physicalchemical.biologicalproperties.J Endocrinol Invest 8225232
  35. 35. Peeters RP, van der Deure WM, Visser TJ2006Genetic variation in thyroid hormone pathway genes; polymorphisms in the TSH receptor and the iodothyronine deiodinases. Eur J Endocrinol 155655662
  36. 36. PeetersR. P.van ToorH.KlootwijkW.de RijkeY. B.KuiperG. G.et al.2003Polymorphism in thryoid hormone pathway genes are associated with plasma TSH and iodothyronine levels in healthy subjects. J Clin Endocrinol Metab 8828802888
  37. 37. PanickerV.CluettC.ShieldsB.MurrayA.ParnellK. S.et al.2008A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine. J Clin Endocrinol Metab 9330753081
  38. 38. AlberobelloA. T.CongedoV.LiuH.CochranC.SkarulisM. C.et al.2011An intronic SNP in the thyroid hormone receptor beta gene is associated with pituitary cell-specific over-expression of a mutant thyroid hormone receptor beta2 (R338W) in the index case of pituitary-selective resistance to thyroid hormone. J Transl Med 9: 144.
  39. 39. DayanC. M.PanickerV.2009Novel insights into thyroid hormones from the study of common genetic variation. Nat Rev Endocrinol 5211218
  40. 40. HorvathA.FauczF.FinkielstainG. P.MENikitaRothenbuhler. A.et al.2010Haplotypeanalysis of the promoter region of phosphodiesterase type 8B (PDE8B) in correlation with inactivating PDE8B mutation and the serum thyroid-stimulating hormone Levels. Thyroid 20.
  41. 41. Arnaud-LopezL.UsalaG.CeresiniG.BDMitchellPilia. M. G.et al.2008Phosphodiesterase 8B gene variants are associated with serum TSH levels and thyroid function. Am J Hum Genet 8212701280
  42. 42. SabetiP. C.SchaffnerS. F.FryB.LohmuellerJ.VarillyP.et al.2006Positive natural selection in the human lineage. Science 31216141620
  43. 43. LópezHerráez. D.BauchetM.TangK.TheunertC.PugachI.et al.2010Genetic variation and recent positive selection in worldwide human populations: evidence from nearly 1 million SNPs. PLoS One 4: e7888.
  44. 44. Dormitzer PR, Ellison PT, Bode HH1989Anomalously low endemic goiter prevalence among Efe pygmies. Am J Phys Anthropol 78527531
  45. 45. HancockA. M.WitonskyD. B.Alkorta-AranburuG.BeallC. M.GebremedhinA.et al.2011Adaptations to climate-mediated selective pressures in humans. PLoS Genet 7: e1001375.
  46. 46. NielsenR.BustamanteC.ClarkA. G.GlanowskiS.SacktonT. B.et al.2005A scan for positively selected genes in the genomes of humans and chimpanzees. PLoS Biol 3: e170.
  47. 47. GagneuxP.AmessB.DiazS.MooreS.PatelT.et al.2001Proteomic comparison of human and great ape blood plasma reveals conserved glycosylation and differences in thyroid hormone metabolism. Am J Phys Anthropol 11599109
  48. 48. NewtonP.1996Hypothyroid nails and evolution. Lancet 34718321833
  49. 49. IwasawaH.1960On the local variation of the thyroid gland in the Japanese pond frog, Rana nigromaculata. Doubutsugaku zasshi 69125128
  50. 50. Woodhead AD, Scully PM1977A comparative study of the Pretumorous thyroid gland of the gynogenetic teleost, Poecilia formosa, and that of other Poeciliid fishes. Cancer Res 3737513755
  51. 51. Moccia RD, Leatherland JF, Sonstegard RA1977Increasing frequency of thyroid goiters in Coho salmon (Oncorhynchus kisutch) in the Great Lakes. Science 198425426
  52. 52. Sonstegard RA1976Studies of the etiology and epizootiology of lymphosarcoma in Esox (Esox lucius L. and Esox masquinongy). Prog Exp Tumor Res 20141155
  53. 53. Moccia RD, Leatherland JF, Sonstegard RA1981Quantitative interlake comparison of thyroid pathology in Great Lakes coho (Oncorhynchus kisutch) and chinook (Oncorhynchus tschawytscha) salmon. Cancer Res 4122002210
  54. 54. MocciaR. D.FoxG. A.BrittonA.1986A quantitative assessment of thyroid histopathology of herring gulls (Larus argentatus) from the Great Lakes and a hypothesis on the causal role of environmental contaminants. J Wildlife Dis 226070
  55. 55. Sonstegard RA, Leatherland JF1979Hypothyroidism in rats fed Great Lakes coho salmon. Bull Environ Contam Toxicol 22779784
  56. 56. Schlumberger HG1955Spontaneous goiter and cancer of the thyroid in animals. Ohio J Sci 552343
  57. 57. HonmaY.ShiodaS.YoshieS.1977Changes in the thyroid gland associated with the diadromous migration of the threespine stickleback, Gasterosteus aculeatus. Jpn J Ichthyol 241725
  58. 58. HamadaK.1975Excessively enlarged thyroid follicles of the threespine stickleback, Gasterosteus aculeatus aculeatus, reared in freshwater. Jpn J Ichthyol 21183190
  59. 59. CabelloG.VilaxaA.SpotornoA. E.ValladaresJ. P.PickardM.et al.2003Evolutionary adaptation of a mammalian species to an environment severely depleted of iodide. Pflug Arch Eur J Phy 4464245
  60. 60. Dunlap KL, Reynolds AJ, Refsal KR, Kerr WW, Duffy LK2008Cross-latitudinal, seasonal and diurnal comparisons in thyroid hormone concentrations in sled dogs. Am J Anim Vet Sci 396103
  61. 61. Burger MF, Denver RJ2001Plasma thyroid hormone concentrations in a wintering passerine bird: their relationship to geographic variation, environmental factors, metabolic rate, and body fat. Physiol Biochem Zool 75187199
  62. 62. FairP. A.MontieE.BalthisL.ReifJ. S.BossartG. D.2011Influences of biological variables and geographic location on circulating concentrations of thyroid hormones in wild bottlenose dolphins (Tursiops truncatus). Gen Comp Endocrinol 174184194
  63. 63. Buchholz DR, Hayes TB2005Variation in thyroid hormone action and tissue content underlies species differences in the timing of metamorphosis in desert frogs. Evol Dev 7458467
  64. 64. Bragg AN1945The spadefoot toads in Oklahoma with a summary of our knowledge of the group. II. Am Nat 795272
  65. 65. Newman RA1988Genetic variation for larval anuran (Scaphiopus couchii) development time in an uncertain environment. Evolution 42763773
  66. 66. Pickard MR, Sinha AK, Ogilvie LM, Leonard AJ, Edwards PR, et al.1999Maternal hypothyroxinemia influences glucose transporter expression in fetal brain and placenta. J Endocrinol 163385394
  67. 67. Wilson CM, McNabb FM1997Maternal thyroid hormones in Japanese quail eggs and their influence on embryonic development. Gen Comp Endocrinol 107153165
  68. 68. Brown DD1997The role of thyroid hormone in zebrafish and axolotl development. Proc Natl Acad Sci USA 941301113016
  69. 69. TagawaM.HiranoT.1987Presence of thyroxine in eggs and changes in its content during early development of chum salmon, Oncorhynchus keta. Gen Comp Endocrinol 68129135
  70. 70. Mc CombD. M.GelsleichterJ.CAManireBrinn. R.BrownC. L.2005Comparative thyroid hormone concentration in maternal serum and yolk of the bonnethead shark (Sphyrna tiburo) from two sites along the coast of Florida. Gen Comp Endocrinol 144167173
  71. 71. Parsons GR1993Geographic variation in reproduction between two populations of the bonnethead shark, Sphyma tiburo. Environ Biol Fish 382535
  72. 72. Arendt JD1997Adaptive intrinsic growth rates: an integration across taxa. Q Rev Biol 72149177
  73. 73. Conover DO1990The relationship between capacity for growth and length of growing season: evidence for and implications of countergradient variation. Trans Am Fish Soc 119416430
  74. 74. HabraM.SarlisN. J.2005Thyroid and aging. Rev Endocr Metab Disord 6145154
  75. 75. Brown-Borg HM2007Hormonal regulation of longevity in mammals. Ageing Res Rev 62845
  76. 76. Hulbert AJ, Hinds DS, MacMillen RE1985Minimal metabolism, summit metabolism and plasma thyroxine in rodents from different environments. Comp Biochem Phys A 81687693
  77. 77. Kwiecinski GG, Damassa DA, Gustafson AW1986Control of sex steroid-binding protein (SBP) in the male little brown bat: relationship of plasma thyroxine levels to the induction of plasma SBP in immature males. J Endocrinol 110271278
  78. 78. BuffensteinR.2005The naked mole-rat: a new long-living model for human aging research. J Gerontol A Biol Sci Med Sci 6013691377
  79. 79. BuffensteinR.WoodleyR.ThomadakisC.DalyT. J.GrayD. A.2001Cold-induced changes in thyroid function in a poikilothermic mammal, the naked mole-rat. Am J Physiol-Reg I 280: R149155
  80. 80. OokaH.ShinkaiT.1986Effects of chronic hyperthyroidism on the lifespan of the rat. Mech Ageing Dev 33275282
  81. 81. LinS. C.LiS.DroletD. W.RosenfeldM. G.1994Pituitary ontogeny of the Snell dwarf mouse reveals Pit-1-independent and Pit-1-dependent origins of the thyrotrope. Development 120515522
  82. 82. SornsonM. W.WuW.DasenJ. S.FlynnS. E.NormanD. J.et al.1996Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism. Nature 384327333
  83. 83. BoylstonW. H.De FordJ. H.PapaconstantinouJ.2006Identification of longevity-associated genes in long-lived Snell and Ames dwarf mice. Age 28125144
  84. 84. VergaraM.Smith-WheelockM.HarperJ. M.SiglerR.MillerR. A.2004Hormone-treated snell dwarf mice regain fertility but remain long lived and disease resistant. J Gerontol A Biol Sci Med Sci 5912441250
  85. 85. HauckS. J.HunterW. S.DanilovichN.KopchickJ. J.BartkeA.2001Reduced levels of thyroid hormones, insulin, and glucose, and lower body core temperature in the growth hormone receptor/binding protein knockout mouse. Exp Biol Med 226552558
  86. 86. KitanoJ.LemaS. C.LuckenbachJ. A.MoriS.KawagishiY.et al.2010Adaptive divergence in the thyroid hormone signaling pathway in the stickleback radiation. Curr Biol 2021242130
  87. 87. BouraD.CastricV.BernatchezL.AudetC.2002Physiological, endocrine, and genetic bases of anadromy in the brook charr, Salvelinus fontinalis, of the Laval River (Que ́bec, Canada). Environ Biol Fish 64229242
  88. 88. RubinC. J.ZodyM. C.ErikssonJ.MeadowsJ. R.SherwoodE.et al.2010Whole-genome resequencing reveals loci under selection during chicken domestication. Nature 464587591
  89. 89. KijasJ. W.LenstraJ. A.HayesB.BoitardS.PortoNeto. L. R.et al.2012Genome-wide analysis of the world’s sheep breeds reveals high levels of historic mixture and strong recent selection. PLoS Biol 10: e1001258.
  90. 90. NakaoN.OnoH.YamamuraT.AnrakuT.TakagiT.et al.2008Thyrotrophin in the pars tuberalis triggers photoperiodic response. Nature 452317322
  91. 91. OnoH.HoshinoY.YasuoS.WatanabeM.NakaneY.et al.2008Involvement of thyrotropin in photoperiodic signal transduction in mice. Proc Natl Acad Sci U S A 1051823818242
  92. 92. HanonE. A.LincolnG. A.FustinJ. M.DardenteH.Masson-PevetM.et al.2008Ancestral TSH mechanism signals summer in a photoperiodic mammal. Curr Biol 1811471152
  93. 93. MasumotoK.Ukai-TadenumaM.KasukawaT.NaganoM.UnoK. D.et al.2010Acute induction of Eya3 by late-night light stimulation triggers TSHβ expression in photoperiodism. Curr Biol 2021992206
  94. 94. DardenteH.CAWyseBirnie.MJDupréS. M.LoudonA. S. I.et al.2010A molecular switch for photoperiod responsiveness in mammals. Cur Biol 2011932198
  95. 95. SchluterD.2000The Ecology of Adaptive Radiation. New York: Oxford University Press.
  96. 96. Barrett RDH, Hoekstra HE2011Molecular spandrels: tests of adaptation at the genetic level. Nat Rev Genet 12767780
  97. 97. SonstegardR.LeatherlandJ. F.1976The epizootiology and pathogenesis of thyroid hyperplasia in coho salmon (Oncorhynchus kisutch) in Lake Ontario. Cancer Res 3644674475
  98. 98. Hewitt EA, Crain DA, Gunderson MP, Guillette LJJ2002Thyroid status in juvenile alligators (Alligator mississippiensis) from contaminated and reference sites on Lake Okeechobee, Florida, USA. Chemosphere 4711291135
  99. 99. GorbmanA.GordonM.1951Spontaneous thyroidal tumors in the swordtail Xiphophorus montezumae. Cancer Res 11184187
  100. 100. BergO.GordonM.GorbmanA.1954Comparative effects of thyroidal stimulants and inhibitors of normal and tumorous thyroids in Xiphophorin fishes. Cancer Res 14527533
  101. 101. BuffernsteinR.PintoM.2009Endocrine function in naturally long-living small mammals. Mol Cell Endocrinol 299101111

Written By

Asano Ishikawa and Jun Kitano

Submitted: 20 November 2011 Published: 18 July 2012