Gathering New Insights Into Genetic Shuffling in Snakes, and the Rest of Us

Carla Hoge, who graduated with a PhD in Biological Sciences in December 2023, and is staying on at Columbia for a short postdoc, just published a research article in the journal Science. Her co-authors include professor Molly Przeworksi and fellow postdoc Marc de Manuel Montero. The paper shows that, in snakes, recombination—a process that reshuffles genetic material during the formation of sperm and egg cells—happens at two separate sites on the snake’s chromosomes, the spindly structures that contain its genetic material. What makes that finding important enough to land it in one of the leading scientific journals? Hoge sat down with Columbia News to explain.

Can you break down this finding for us? What is the significance of recombination happening at two sites in snakes?

Most cells replicate through a process called mitosis, which results in two cells that are identical to their parent cell. But sex cells—sperm and eggs—form through a process called meiosis. In meiosis, one parent cell creates four offspring cells with half the chromosomes of the parent cell.

In the first stage of meiosis, in order for chromosomes to properly separate, they first need to bind together physically. DNA is shuffled between chromosomes during this process. The shuffling process helps distribute the right number of chromosomes into egg or sperm, and is called recombination.

Recombination is interesting because once it happens, the chromosomes are no longer identical to the parent’s chromosomes. Chromosomes in sperm, for example, are a mosaic of bits and pieces from the two parents of the male.

Despite recombination being fundamental and necessary for meiosis, it has evolved in many different ways between organisms, which is surprising. Usually, processes that are necessary for life are more conserved over generations.

Recombination happens in a couple of different ways in different species. In many mammalian species, like humans and mice, recombination occurs with the help of a protein called PRDM9, which binds to the chromosome. For these species, recombination begins at a subset of sites to which PRDM9 binds.

But some animals have, in the course of evolution, lost PRDM9, and in those organisms, recombination generally takes place at “promoters,” which are the locations on the chromosome where genes start.

The main takeaway from our paper is that we thought these two starting points for recombination were mutually exclusive, but what we actually found is that corn snakes use both, and there’s a very good chance that other vertebrates do, too.

What got you interested in this area of study?

Before I joined Professor Molly Przeworski’s lab, they had put out a paper on the evolution of PRDM9. The paper’s findings led to this hypothesis that PRDM9 should be functioning the same in all vertebrates as it functions in mammals, where its role is reasonably well understood. At Columbia, as a grad student, you try out labs before committing to one, and Molly suggested that I do my trial run in her lab, working with a graduate student who was following up on that hypothesis. We thought it would be a quick project, but six years later, we’re still working on PRDM9. We’ve found a lot of really interesting things!

Why did you choose to look at snakes?

We chose snakes because we thought that they’d be a representative vertebrate species. By looking at snakes, we could examine phenomena that are likely happening in other vertebrates like birds, mice, or people.

What makes recombination an important phenomenon for scientists to study right now?

Recombination is fundamentally important, but it’s also evolving quickly in many different ways between species. It’s quite surprising for an evolutionary biologist to see something that is necessary for a species' reproduction and survival changing so frequently and significantly across generations.

What do you like to do in your spare time?

I really like theater. I did theater a lot in college, and I have friends that are involved in theater in the city, so I go to plays whenever I can.

Have you seen anything you’d particularly recommend?

I’m trying to win lottery tickets for Merrily We Roll Along.

I saw How to Dance in Ohio and Kimberly Akimbo, and found them both really powerful. Kimberly Akimbo dealt with some heavy topics, but at the same time, it was a really fun show, and the plot moved right along.