June 28, 2022 | Jerry Bergman

Adult Body Proportions Partly Solved

Progress in solving the mystery of adult-size similarity in animals:
New genetic process sheds light on how organ proportionality works

 

It’s an intriguing mystery: how can there be size differences in adult members of the same species?

The author’s Cavopoo (aka Cavoodle and/or Cavadoodle), a cross between a Cavalier King Charles Spaniel and a Poodle.

Consider the enormous size differences in animals such as dogs. I have an 8-pound Cavalier King Charles Spaniel-Poodle mix (Cavapoo) and my daughter has a 230-pound Mastiff. Each dog’s body and organs are correctly proportioned to their size, even though the Mastiff is 28 times more massive than our Cavapoo. Our small dog has perfectly sized internal organs and body parts for his size and weight, and the Mastiff likewise has the required proportions of organs and body parts for its size. Something controls these results. A press release on June 7 from the Friedrich Miescher Institute for Biomedical Research in Germany relates the mystery:

developmental regulation of final body and organ size is fundamental to generating a functional and correctly proportioned adult. Research over the last two decades has identified a long list of genes and signaling pathways that, when perturbed, influence final body size. However, body and organ size are ultimately a characteristic of the whole organism, and how these myriad genes and pathways function within a physiological context to control size remains largely unknown.[1]

Research by Benjamin Towbin and his students at the University of Bern attempted to determine how a myriad of genes and pathways function to control the sizes and proportions of organs within the body. When born, the Mastiff and Cavapoo dogs were close to the same size, but the adult outcomes were dramatically different, even though they are both members of Canis familiaris. Usually, “adults of the same species are usually nearly identical in size.”[2] How does development proceed so that the stomach, heart, liver, ears and tongue know when to stop growing?

The dramatic differences in dog sizes between breeds.

Breeders can cross a large dog with a small dog and get a pup of intermediate size whose organs are appropriate for its terminal size. A Dachshund has a trunk close to the size of a typical small dog, but very short legs. When a Dachshund is mixed with a poodle, the Dachshund limb size is retained but the poodle hair dominates. Since Mendel’s famous work on peas, scientists have known that traits are determined by genes.

Towbin acknowledged that little is known about how multicellular animals control their terminal body size with proportionally-sized organs to match. He tested a new hypothesis after wondering how

individuals of the same species grow to the same size. This uniformity in size is astounding, since intrinsic randomness in developmental processes and in environmental conditions produce substantial differences in how fast individuals grow. Moreover, because animal growth is often exponential, even small differences in growth can amplify to large differences in size. How do animals nevertheless make sure to reach the correct size? [3]

This was the focus of Towbin’s research, and his findings surprised most everyone.

Mechanism Far More Complex Than Previously Believed

Using time-lapse photography, Towbin’s team watched the development of hundreds of roundworms. They found that an inbuilt mechanism exists

that ensures the uniformity of body size among individual animals. The mechanism does not appear to measure size per se. Instead, it senses how fast an individual grows and appropriately adjusts the time after which this individual turns adult. Therefore, a slowly growing individual reaches the same size as a rapidly growing individual because it is given more time to grow.

This inbuilt mechanism couples the growth rate to the frequency of what they called a genetic oscillator that functions as a developmental clock. After four oscillations, juvenile development ends and the animal progresses into the adult stage where animal growth and development largely ends.

To test his theory, Towbin sped-up the genetic oscillator. The result was the animals with the faster clock developed into adults more rapidly but grew smaller in size as adults. This suggests that they grew through the last oscillation too rapidly, and that did not allow enough time to grow to the programmed size for the worm. This genetic oscillator, if confirmed for other animals, appears to be an additional design feature during development. If so, it adds to the complexity of animal growth. Do all animals possess this system?

Answering this question awaits new research, but it is likely that the system is universal in animals, or at least another system serving the same function exists in the animal world. How does it work? The genetic oscillator involves an ultrasensitive feedback system between an activator protein A and a repressor protein R which controls growth. Up-regulation of activator protein A and down-regulation of repressor protein R, will increase growth. The opposite action will reduce growth.

One more required process was discovered. This one involved proper growth development that determines the adult size, which is also limited by several factors including genetics.[4]

Summary

Myriads of genes and pathways within an organism control its adult size and keep its organs in the right proportions. Towbin’s study has opened up a new window into the complexity of animal development. None of the sources in the references below postulated how this system could have evolved in a gradual way. As development of an animal proceeds from an embryo to an adult, it must be able to meet the needs required for life at each stage. This, in turn, requires control systems to regulate the growth of each organ during each stage of development. The fact is, the most

striking characteristic of the growth of mammals is that it is self-stabilizing, or, to take another analogy, “target seeking”. Children, no less than rockets, have their trajectories, governed by the control systems of their genetical constitution and powered by energy absorbed from the natural environment. Deflect the child from its natural growth trajectory by acute malnutrition or a sudden lack of a hormone, and a restoring force develops so that as soon as the missing food or hormone is supplied again the child hastens to catch up toward its original growth curve. When it gets there, the child slows down again, to adjust its path onto the old trajectory once more.[5]

The Towbin research only gives a few details as to how animals reach their normal adult size. As our understanding of animal biology increases, we see its complexity increase. Concurrently, the plausibility of evolution decreases.

References

[1] Gokhale, R.H., and A.W. Shingleton. Size control: the developmental physiology of body and organ size regulation. WIREs [Wiley Interdisciplinary Reviews] Developmental Biology 4(4): 335–356, July/August 2015.

[2] Friedrich Miescher Institute for Biomedical Research. How animals reach their correct size. https://www.fmi.ch/news-events/articles/news.html?news=546, 7 June 2022. [A review of: Stojanovski, Klement, Helge Großhans, and Benjamin D. Towbin. Coupling of growth rate and developmental tempo reduces body size heterogeneity in C. elegans. Nature Communications 13: 3132, 2022.]

[3] Friedrich Miescher Institute for Biomedical Research, 2022.

[4] Blanckenhorn, W.U. The evolution of body size: What keeps organisms small? Quarterly Review of Biology 75(4): 385–407, December 2000.

[5] Tanner, J.M. Regulation of growth in size in mammals. Nature 199(4896): 845–850, 31 August 1963.


Dr. Jerry Bergman has taught biology, genetics, chemistry, biochemistry, anthropology, geology, and microbiology for over 40 years at several colleges and universities including Bowling Green State University, Medical College of Ohio where he was a research associate in experimental pathology, and The University of Toledo. He is a graduate of the Medical College of Ohio, Wayne State University in Detroit, the University of Toledo, and Bowling Green State University. He has over 1,300 publications in 12 languages and 40 books and monographs. His books and textbooks that include chapters that he authored are in over 1,500 college libraries in 27 countries. So far over 80,000 copies of the 40 books and monographs that he has authored or co-authored are in print. For more articles by Dr Bergman, see his Author Profile.

 

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