**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.
