Species-specific pace of development is associated with differences in protein stability

I think this is a really interesting additional answer to questions about how developmental differences can be explained in animals that are closely related but very different in size or structure. Previously at PS we have discussed differences (between humans and other mammals) in the number and organization of neurons in the brain. That story involves a new human-specific protein that affects mitochondria.

Besides new proteins that bring new functions, there are other ways to make broad changes in development: new regulatory connections, tweaking of signaling systems, etc. But what if the difference that you’re trying to understand is something more global than that? Specifically, consider this very interesting question, from the structured abstract of a new paper in Science:

What determines the pace of embryonic development? Although the molecular and cellular mechanisms of many developmental processes are evolutionarily conserved, the pace at which these operate varies considerably between species. The tempo of embryonic development controls the rate of individual differentiation processes and determines the overall duration of development. Despite its importance, however, the mechanisms that control developmental tempo remain elusive.

They find that one answer is that protein stability can vary significantly between lineages, and that this can explain why development proceeds so much faster in, say, mice than in humans.

Here is the lay summary from Science:

Setting the tempo for development

Many animals display similarities in their organization (body axis, organ systems, and so on). However, they can display vastly different life spans and thus must accommodate different developmental time scales. Two studies now compare human and mouse development (see the Perspective by Iwata and Vanderhaeghen). Matsuda et al. studied the mechanism by which the human segmentation clock displays an oscillation period of 5 to 6 hours, whereas the mouse period is 2 to 3 hours. They found that biochemical reactions, including protein degradation and delays in gene expression processes, were slower in human cells compared with their mouse counterparts. Rayon et al. looked at the developmental tempo of mouse and human embryonic stem cells as they differentiate to motor neurons in vitro. Neither the sensitivity of cells to signals nor the sequence of gene-regulatory elements could explain the differing pace of differentiation. Instead, a twofold increase in protein stability and cell cycle duration in human cells compared with mouse cells was correlated with the twofold slower rate of human differentiation. These studies show that global biochemical rates play a major role in setting the pace of development.

Full paper linked below, and as always, PDF available on request.

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Seems like this is an N=2, with just human and mouse. That leaves a lot of open questions. I wonder what sort of relationships between longevity, body mass, mutation rate, etc. and protein stability might be uncovered with a more complete dataset. I also wonder if humans are an outlier in any of these trends or not.

It is misleading to refer to the study in that way, and specifically it is inappropriate to use the phrase “n=2” to describe this comparative work. We use that phrase to describe sampling limitations. This paper is about one way to explain the big differences in tempo between those two species.


Yeah, that would be confusing shorthand. I just meant N=2 in terms of species, not individuals or cell lines. I’m sure their replications were higher than just 2. I am just curious what it will look like to fill out the story with data from more species.

I think the next step is not to explore phylogenetics but to find the mechanism. This is a case where the difference between the two species is the important observation but the big question is what causes it. Not whether it’s the case in other lineages. Because even if one of those two species is an outlier, the observation is that overall protein stability is an adjustable factor in development. The authors say that the mechanism is the next big question and I agree. Then the phylogenetics can happen.

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I think answering the cause vs effect question is an important one too.