Testing the Thyroid Rhythm Hypothesis
My thyroid hormone theory for how speciation works is scientific because it's testable: here's what needs to be done
[Adapted from my 2006 book, Rhythms of Life, with selected references, including some updated ones]1
Ultimately, the reason my theory that thyroid hormones play a critical role in evolution—including human evolution—is so important, is because my hypotheses are testable.
Being testable is what makes this theory scientific and distinguishes it from other wishful-thinking narratives and “just-so” stories of how species arise.2
Thyroid rhythm theory assumes that individually-unique thyroid rhythm variants exist within species-specific patterns for animal populations and that these thyroid rhythm variants are the actual characteristics targeted by natural selection in instances of adaptation and colonization.
The model predicts that non-random subdivision of populations often occurs during speciation, isolating particular subsets of individuals with similar thyroid rhythms within founder populations. Developmental repercussion of reduced thyroid rhythm diversity in the founding group is assumed to be responsible for generating the particular growth and development changes seen in descendant taxa.
The basic hypothesis to be tested, therefore, is that daily rhythmic thyroid hormone (TH) secretion profiles in any vertebrate species are individually variable and that these variations between individuals can be correlated with discernable physical, reproductive and behavioural differences, generating thyroid rhythm phenotypes.
As a group, individual thyroid rhythm phenotypes together should generate a distinctive pattern for the population that is species-specific (or in the case of domesticates, breed-specific); that is, the average pattern for the group should be distinguishable from that of a closely-related species.
Devising experiments that can reliably test this premise will undoubtedly be difficult due to the dynamic nature of the endocrine system and its inherent sensitivity to stress of any kind. Such sensitivity presents a unique challenge to the determination of normal thyroid rhythms within and between taxa, since TH levels must be measured frequently (at least every 5–7 minutes, perhaps as often as 2.5 minutes), under controlled conditions and for many individuals.
Experimental tests have demonstrated that automated sampling may circumvent many of the difficulties of testing the thyroid rhythm hypothesis.
For one study, which measured levels of the adrenal hormone corticosterone in rats, a surgically implanted cannula connected to an automated blood-sampling apparatus allowed minute quantities of blood (10–20 μl) to be collected every ten minutes over a twenty-four-hour period without disturbing the animals by repeated handling.3
The two breeds of rats used in this study had significant differences in mean profiles of hormone production (as well as slight individual variations within breeds) in addition to significant differences in behavioural responses to a controllable stress (so-called white noise). The success of these experiments in demonstrating the existence of fine-scale patterns of corticosterone production and in correlating these profiles to stress responses suggests that a similar method might be suitable for testing the thyroid rhythm hypothesis.
Similar automated sampling methods have also been applied to studies on pulsatile hormone secretion in humans and a range of other species—including cats, rats, horses, cattle, chickens, frogs and fish. In my opinion, such active areas of research simply need an over-arching paradigm to put the results into evolutionary context.4
While huge advances have been made in measuring cortisol, the adrenal stress-hormone analogue to corticosterone found in fish, humans, and other medium to large sized mammals, doing something similar for TH presents unique problems.5
That’s because current laboratory assay methods for measuring T3 or T4 in minute quantities (as opposed to measuring TSH - thyroid stimulating hormone or thyrotropin) may place limitations on the smallest samples that can be analyzed. So unless it can be demonstrated that using TSH is superior for this particular purpose, it means new assay methods may need to be developed.6
The sampling apparatus itself may need modification to allow testing of a full range of animals: laboratory-housed fish species and free-ranging bears, for example, pose very different logistical problems for an automated TH sampling device.
However, the advances in similar devices have been made over the last two decades suggest that success with TH sampling tools are within reach.
If individual variation within species-specific profiles of thyroid rhythms can be confirmed, controlled breeding experiments – similar to those described for silver foxes – will be necessary to confirm that small interbreeding groups of animals with similar thyroid rhythm profiles produce descendants of a different type within twenty generations or less.
[Although a few experiments of this nature have been done, so far they lack the necessary sampling of incremental TH levels.]7
It would be most convincing if descendants of such breeding programs could have their thyroid rhythm profiles monitored as well, for these should differ from the original source population.
If it can be demonstrated that thyroid rhythms are indeed variable within certain limits for different populations (or breeds, or for certain morphs within species) and that heterochronic changes can be generated by interbreeding small groups of physiologically similar individuals, the final step will be to find the genetic sources of those pattern differences.
Although species-specific thyroid rhythms are probably controlled by genes in the suprachiasmatic nucleus (SCN) of the hypothalamus that are directly associated with generating hormone pulsatility, other factors may affect thyroid hormone utilization in ways that are also species-specific, such as the different concentrations of the thyroid hormone-transporting molecule transthyretin found in chimpanzees and humans by one research group.8
Mutations in genes controlling other aspects of thyroid-mediated actions in target tissues (such as receptors, receptor ligands and/or cofactors) are also potential causes of variation.
However, it is expected that in most cases, differences in such genes will be found to supplement, compound, or confound thyroid rhythm effects, rather than contribute to their initial rhythmic generation – and as a consequence, genes involved in such thyroid hormone-mediated “end-factor” processes could be selected for independently from thyroid rhythms or simultaneously. This means that mutations in such genes may explain the origins of some evolutionary novelties that are not developmental in nature.
I suggest that the first step in genetic characterization of individual and species-specific thyroid rhythm profiles should start with documenting variation in SCN output.
In the meantime, ongoing research into the regulatory mechanisms of embryonic development should unravel some of the essential molecular interactions that involve thyroid hormones and thyroid rhythms.
Research on Hox genes that act during embryonic development has thus far revealed they respond to retinoic acid as well as to other molecules. In light of the known developmental regulation functions that retinoic acid shares with thyroid hormone, or in which their roles cannot be distinguished, it would be prudent for researchers to look at the response of Hox genes to TH and thyroid rhythm pulses, in combination with retinoic acid.9
Given the critical roles recently demonstrated for thyroid hormones themselves in embryonic development, we also need to know what effects different thyroid rhythm profiles might have on any given developmental program.
Lastly, research into the physiological and genetic basis of natural piebaldness (rather than aberrant whitespotting mutants) may also be illuminating. Piebaldness, if we can come to understand exactly what it signifies in an evolutionary context, could serve as an especially useful diagnostic marker for developmental change.
As I’ve said before:
While this paradigm challenges one of the accepted tenets of neo-Darwinian theory ─ that evolution is due almost exclusively to the gradual accumulation of random genetic mutations and as a consequence is almost always imperceptibly slow ─ it more accurately reflects and predicts the complex nature of inter- and intra-specific relationships we are now able to discern from phylogenetic analysis of closely related species, including our own ancestors. Significantly, it can explain the big, body-plan changes associated with macroevolution that are often seen as problematic.
My hypothesis offers an explanation that plugs many of the gaps in our understanding of how and why speciation works. If it is not this mechanism exactly, it must be one like it.
The only way to find out if the mechanism I’ve described is entirely correct, or only partially so, is to undertake the kinds of tests described above, which are too multi-faceted to fall on one person (me). My job was to formulate the paradigm and lay out its foundation and the associated hypotheses, which I did in my 2004 dissertation: the actual work of testing it falls to a new generation of evolutionary biologists looking to make their mark.
Crockford, S.J. (2006). Rhythms of Life: Thyroid Hormone and the Origin of Species. Trafford, Victoria.
See also: Crockford, S.J. (2004). Animal Domestication and Vertebrate Speciation: A Paradigm for the Origin of Species. Ph.D. dissertation. University of Victoria, Canada. http://hdl.handle.net/1828/542
Horrobin, D. (2001). The Madness of Adam and Eve: How Schizophrenia Shaped Humanity. Bantam Press, London. [I met Dr. Horrobin before he died and we talked extensively about speciation mechanisms: he agreed that my hypothesis was was testable as an evolutionary theory and his was not]
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