Bickel, R. D., Cleveland, H. C., Barkas, J., Jeschke, C. C., Raz, A. A., Stern, D. L., & Davis, G. K. (2013). The pea aphid uses a version of the terminal system during oviparous, but not viviparous, development. EvoDevo, 4(1), 10. doi:10.1186/2041-9139-4-10
Ladies and gentlemen, I have spent the past few days struggling to find a way to write about the CRISPR genome-editing revolution. The CRISPR system is a truly profound breakthrough that uses just two molecular components to remove, add, or otherwise edit any gene in any living thing. Component One is an enzyme called Cas9, which cuts DNA, and Component Two is a fragment of RNA that can easily be made to guide Cas9 to any specific place in the genome. It’s insane. This system was co-opted from an anti-viral immune system that naturally occurs in yogurt bacteria, and in the past few years it has been shown to work in basically every organism on the planet, and to work very well. At this point, just two years after the system really came of age, it appears routine to systematically screen the entire human genome for cell growth phenotypes in a single flask of human cell culture in about a week.
I was thinking that I’d write about this insanely hot pape, coming from the lab of the hero that discovered introns and exons, where they made a library of guide RNAs targeting every gene in the mouse genome, transfected these RNAs into a flask of cells capable of forming tumors but not of metastasizing, and injected the resulting cells into mice. A few weeks later, they found that some of these genotypically mosaic tumors had indeed metastasized, and by sequencing the mutant cells found in the spreading tumors they could identify what gene had been mutated in those tumor cells, and from a grand total of like six mice, they had a list of genes whose absence can lead to tumor metastasis.
But as I started to write, something just didn’t feel right. As undoubtedly dope as these CRISPR papes are, I just couldn’t shake the feeling that these huge CRISPR labs really aren’t really my crew. Maybe it was checking out these two CRISPR-based biotechnology companies whose websites literally just list their scientific advisors and how many millions of dollars they’ve raised from investors. I dunno - absolutely no disrespect to the jaw-droppingly productive authors of the CRISPR revolution, but I just can’t help but think about the staggering funding inequality amongst biology labs, and the growing pressure to focus on research that has direct applications to human medicine, and in the end I just felt like my heart wasn’t in it. Ladies and gentlemen, I had to walk away from that Sick Papes post, as difficult as it was.
Then I came home and re-read this wonderful paper about aphid development, chock full of undergraduate co-authors and off-the-wall insect evolution, and felt a wave of warmth and safety rush over me. The paper deals with aphids, which have one of the most bizarre lifestyles on earth: all year long, female aphids give birth to clonal female babies via virgin birth, no males involved. THEN, right before winter, they make one generation of males, which undergo normal meiosis and sexual reproduction with their female siblings, to produce an egg that is capable of over-wintering. This is the egg that will hatch in the spring to give rise to another female who will then start clonally reproducing female babies via virgin birth all over again.
So the idea is that we have basically one animal, with one genome, but with two completely different modes of embryonic development depending on the time of year. In one mode, they develop clonally within their mother’s ovary, whereas in the other they develop from a more typically insect egg. In this paper, the authors look at some interesting differences in gene expression between these two modes of development, to start to hone in on how a single genome can accommodate two distinct lifestyles. For sure, there are a few question marks in their final figure, but god DAMN does a paper like this make me remember why I love biology so much: a bunch of students studying the trippiest things they can think of, and revealing some strange and mysterious detail of how animals work. Happy Spring to all of you!