Study: Parallel shifts in differential gene expression reveal convergent miniaturization in fishes (DOI: 10.1073/pnas.2512299122)
Imagine you are a kind of fish called a goby, part of a huge family of more than 2,000 species.
Maybe you're of average size for a goby, about three to four inches long. Your longest relative is about four times your length-more than a foot long. Your smallest relative is similarly about four times smaller than you, clocking in at under an inch.
In human terms, that's like having one cousin who's 22 feet tall and another cousin who's just over a foot tall.
University of Michigan postdoctoral researcher Emily Troyer led work investigating why gobies exhibit such a size range, focusing in particular on how gobies are able to regulate size in order to stay miniature. She found that certain gobies overexpress two genes that inhibit growth, keeping some species of goby miniaturized.
Additionally, by looking at different groups of gobies across time, she found that miniature gobies have used the same genetic pathways to regulate their size since the Eocene, more than 50 million years ago. The work, supported by the U.S. National Science Foundation, is published in the Proceedings of the National Academy of Science.
"Body size is probably the most critical organismal trait. It's linked to so many biological processes, from metabolism to reproduction," Troyer said. "So by understanding the controls over body size, this not only has implications for evolutionary biologists, but maybe also biomedical scientists who want to understand the growth of tumors."
Troyer says the underlying genetics of body size has remained a question for scientists. Understanding how organisms control their body size is important because size determines many other components of an organism's existence, such as where it lives, what it eats, the shape of its body and how it reproduces.
"We understand a little bit about the why. So if you're small, you might be able to fit into these tiny microhabitats and live there. Some of these gobies are so small, they spend the entirety of their lives within a single head of coral, with a two-square-meter range," Troyer said. "What's a little less understood is the genetics of why this is happening. We wanted to take a stab at this question using gobies as our model system."
In particular, the genes that Troyer identified in miniature gobies, CDKN1B and ING2, are both associated with regulating and limiting the number of cells grown in the goby.
To determine which genes were most associated with body size, Troyer created a phylogeny, or family tree of 162 goby species. Troyer and her co-authors then focused on three groups of gobies that exhibit repeated instances of both miniaturization and large-bodied forms.
To examine the difference in gene expression between miniature and large-bodied gobies, the researchers used comparative transcriptomic techniques. Your genome loop contains the genetic information that allows your body to produce proteins necessary to carry out different functions. Your transcriptome is the set of RNA molecules transcribed from those genes to produce proteins. In essence, the transcriptome provides a snapshot of which genes are "turned on" or actively expressed at a given time.
This allowed the researchers to see which genes were associated with growth. Using a method called differential gene expression analysis, the researchers compared the levels of gene activity between large- and small-bodied gobies to pinpoint which genes were turned up or down in each group.
They found that in miniature gobies CDKN1B and ING2 were highly upregulated, or highly turned on, in miniature species. By contrast, genes associated with cell multiplication and proliferation were highly upregulated in the larger goby species.
CDKN1B in particular was an interesting find, according to Troyer. This gene is known to be an inhibitor of growth, and it does this by blocking cell division at a certain point during the cell's typical cycle of division. This limits overall cell proliferation, or how much cells can grow and divide.
Interestingly, this gene has also been found to control body size in mice, Troyer said. When this gene is knocked out, or deleted, from mice, they grow to be two times larger than normal mice due to increased cell numbers.
"Most of our understanding of these processes comes from model organisms like mice and fruit flies. We know next to nothing about nonmodel species, especially random gobies," Troyer said. "This finding was another cool parallel that we found in nonmodel species, but it's actually happening in model species as well."
Dahiana Arcila, an evolutionary biologist at the Scripps Institution of Oceanography, is the senior author of the study.
"It's remarkable that the same genetic mechanisms controlling body size in mammals and other model species are also at work in these tiny coral reef fishes," she said. "By tracing these patterns across millions of years, we're learning that the rules of growth and size are deeply shared across vertebrates."
