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Something Good: The Zoonomia Project

I’ve said before that humans are amazing creatures.

(Picture from here.)

We are incredibly smart—so smart that we forget how smart we are when we do stupid things or find minimal common ground with other animals. “Well, if a myna bird can use tools, they must be on a par with us. Therefore, tool using isn’t such a great thing.” Forgetting, for the moment, that while a myna bird might use a stick or a chimp might solve a maze, neither has built computers, sky scrapers, trains, or managed to get off earth into space.

You can argue the value of these things but you can’t argue we did it.

Every now and then we outdo ourselves. The Zoonomia Project is an example.

Mammals arose 200 million years ago, around the same time dinosaurs began taking off. The two groups do have a stem ancestor long ago but very few of the traits that dinosaurs, crocodilians, birds, etc., have any shared origin with mammals.

However, mammals do have a lot of shared ancestry with each other. Mammals died back, diversified, radiated, rinse and repeat, over tens of millions of years. But many of the ancient lineages died during the Cretaceous extinction along with other animals. This means that modern animals derive from a lot of common stock. Primates, bats, cows, dogs, and cats, all originated either just before the extinction event or somewhat after. By examining the differences, it could be possible to tease out how any individual group pulled their physical characteristics from the originating material.

The Zoonomia Project, carried out jointly at MIT and Harvard, took 240 diverse animals and fully sequenced their genes. Then, they compared the codes against each other. That this was done at all is a terrific achievement. That this was done now is especially interesting. The Human Genome Project finished over twenty years ago but at that time not much was known about the sequences. Then, sequencing techniques improved enormously, gene roles began to be understood, and genetic alterations became an established scientific operation. We don’t know all that much—there is a lot to know—but we know a whole lot more than we did then. Enough to perhaps understand what we’re seeing.

And we’re seeing a lot.

The April 28 2023 issue of Science has several papers released from Zoonomia, all of which are exciting.

The first order of business is pure accounting: what changed between these lineages and how much? Evolution is a constant tug-of-war between innovation and conservation. Innovation introduces new genetic behavior. This could be sequences moved, changed, or deleted. All of which could have an effect but could also be deleterious or result in no change at all.

Conservation, however, prevents change. There’s no point in improving an existing system. This is especially true for very important systems since innovating involves the risk of losing the behavior that makes the sequence important in the first place. Hemoglobin is a good example for this. Hemoglobin is extremely efficient in capturing and releasing oxygen appropriately. It is highly conserved.

Therefore, seeing which sequences have been innovated vs sequences that have been conserved across species gives us an insight into what is important to mammals as a whole.

Innovation and conservation aren’t just common to mammals, thought. This is also important to individual groups of mammals. One group might innovate in a sequence that another group might conserve.

Analyzing this is the province of the Christmas, and others, paper. Innovation reflects selection across a set of sequences. Sequences that show a great deal of change over time reflect rapid evolution. Sequences that show little change (highly conserved or constrained) within a group should reflect those qualities that evolution has shaped in the lineage. Knowing the nature of cats, we might expect a fair amount of conservation of those genes that reflect their behavior and their indicative collective traits.

Because we are who we are, we looked first to those traits we like about ourselves: brain size. They also looked at sense of smell, and hibernation.

One of the interesting results the Christmas paper is that many conserved sequences had no known function. In addition, they discovered that at least 10% of the genome is functional. Since about 1% actually codes for proteins, a whole lot of the genome is bent around the task of regulating expression rather than actual expression.

It is very clear this comparator tool is extremely useful.

The Zoonomia data is already serving up interesting papers outside the project. One is Katie Pollard’s work with human accelerated regions (HARs) in the human genome.

Pollard has been working the HARs for some time. Pollard’s HARs are enhancers, dialing gene expression up or down during development—especially during brain development. Working on concert with the Project, Pollard has been examining why HARs happened in the first place. She found that about a third of the HARs between humans and chimps involved how DNA was folded. This seems to suggest that the structural nature of DNA might have something to do with brain development.

They hypothesis is that by changing the structural folding of DNA within the cell, HARs were brought into closer proximity to genes responsible for brain development. I.e., the genetic sequence responsible for brain development is brought close to an HAR that enhances its activity.

Pollard’s work suggests that a random sequence mutation might have been the originating impulse for our brain development.

This doesn’t surprise me: this is exactly where randomness usually appears. Consider that humans derive from primates, animals with two eyes pointing forward, the perceive color, with very nice hands, and a fair starting brain. This was fertile ground to take advantage of increasing brain capability. Once that variation in capability was available, evolution jumped right on it. Chimps haven’t changed much in the last few million years since we split from them but we have.

Another paper, lead author Foley, attempts to build a timeline of mammalian evolution. This timeline suggests a significant increase in diversity prior to the Cretaceous extinction that was exacerbated after the dinosaurs were taken out of the way.

There are eleven papers in that Science issue. Every one of them is gold.

Nice to feel good about being human once in a while.



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