January 1, 2023 marked Kevin Wei’s first day as an Assistant Professor in the Department of Zoology at UBC. Kevin's office is located at Life Science Institute building, joining the Cell and Developmental Biology research group.
After undergraduate graduation, Kevin spent a year in Taiwan working as a lab technician studying Drosophila evolutionary genetics, which set him on his research path.
Why was that experience in Taiwan so important in your career trajectory? What caught your interest?
To be perfectly honest. I always really enjoyed biology growing up and part of it was that growing up I thought I was going to med school because that seemed to be the obvious thing to study. But that didn’t happen. What I really enjoy with genetics is how much of it feels like very fun puzzles to be solved. There are some very basic rules in genetics, e.g. independent assortment, yet it is an intricate system that is the basis of life. What particularly makes me love Drosophila genetics is that you are given all these rules and all these tools to get at the questions you want answered. It is the puzzle aspect of it that I find very attractive. And by solving these puzzles we can get at basic questions about how organisms are formed and how this system is perpetuated, and the evolution aspect of it all.
Do you think you will keep working with Drosophila or would you expand to other organisms?
I do have a soft spot for flies but definitely open to work with other systems. It will probably be dictated by how funding goes and funding sources. But what we learn from fundamental biology in Drosophila will be readily applicable in mammals, including mice or humans. So, I am definitely thinking about taking what we learn from flies and apply some of the methods and ideas in more translatable systems.
What are the main research methods you use in your lab?
I do a lot of things. Lots of genetics: CRISPR, transgenics, genomics: RNAseq, whole genome sequence, genome assemblies, imaging confocal and electronic microscopy. My work is question driven and I aim to find the right techniques to tackle those questions.
Tell us a little more about your work with transposable elements and selfish genetic elements
In the past, there was this idea that all genes are working together to support life and the host’s fitness - making sure the host organism has functional cells, organelles, organs and body. In actuality, the genome is littered with a lot of “garbage” - DNA that doesn’t seem to have any function - including selfish genetic elements. The major constituents of selfish genetic elements are transposable elements (TEs). We call them “selfish” because they don’t really “care” about the fitness of the host organism, but their primary concern is their own fitness. TEs can replicate in a very unique manner - they self-replicate and move around to increase their copy numbers in the genome. In contrast most genes cannot do that and their success depends on the whole organism’s success. This makes TEs very unique because their interest is not aligned with the that of the host organism. In fact, there is an ongoing conflict because TEs wanting to jump around and increase their copy numbers which favour their own fitness. But that is bad for the whole genome because these TE movements can be highly disruptive for example they can jump into a gene and disrupt the gene’s function.
There is this profound antagonistic interaction between transposable elements (TEs) and the host genome because of the propensity that TEs can create genome instability, damages in the DNA, and ultimately to the whole host genome. This is what we call a molecular arms race: transposable elements have their own interest which is to increase in copy numbers but this has potentially negative effects on the genome. Fortunately, the genome has very sophisticated and often redundant mechanisms to suppress TEs from moving around. Then in turn, TEs can and have evolved ways to evade the suppression and keep jumping around. So this creates this loop of TEs evading defenses and the genome updating these defenses and adapting to the new TEs mechanisms and so on. Usually, these are mutations causing changes to allow TEs to proliferate and those mutation will then propagate in all their copies. Then, as a response the genome will have itself beneficial mutations in silencing TEs. This is an arms race that doesn’t end - or that we don’t foresee ever ending, between the genome and all these selfish genetic elements has driven profound changes in the genome. It is in fact a very old arms racethat can be found across all life forms.
Are there diseases associates to TEs?
There are several ways this could be disease causing. For instance, a transposable element jumping into the functional part of a gene can destroy the gene. If it jumps into an exon, it can cause a malformation of that gene’s products. It can also jump into the regulatory elements and change the gene’s regulation. There are also particular insertions that can be a deleterious allele, often in recessive alleles. A homozygous for those recessive alleles might have a genetic abnormality that would manifest in the individual. There are a lot of TEs can induce diseases.
There are also a lot of examples of TEs inducing positive change in the genome. There are examples of TE insertions that are now essential for the genome. There is a fun one recently published: the authors found evidence that in the macaques and apes primate lineage, tails were lost because of a TE insertion. It turned out the TE insertion caused the loss of tails by changing the splice product of a gene needed for tail development. While the TE insertions occurred in a primate lineage, the researchers were able to test the two splice different variants in mice and show that the variant with the TE insertion created mice with shorter tails.
So, while we primarily think of TE activities as either neutral or deleterious, they can also be drivers for novel phenotypes and genotypes in organisms. And that makes TEs really fascinating to me. A good analogy for the “genome full of garbage” would be the like a garage full of junk. Most of the stuff are just sitting there not doing anything or maybe really annoying in creating clutter. It’s may not be a good idea to have too much clutter in there because things might topple over – that would be really bad, but then maybe sometimes some of the stuff become very useful.
In your lab, is the research on TEs the main questions and is Drosophila the system your use to answer your scientific questions?
The other branch of my research is to understand meiotic recombination, which is the process of homologous chromosomes crossing over during meiosis. This is a very important process because it allows chromosomes to exchange alleles, creating new allele combination. If you don’t have recombination, the lineage is effectively destined to go extinct. This is a very fundamental genetic process that is ancestral to all eukaryotes and is of course taught in Intro genetics classes. There are several interesting things about meiotic recombination that I study in Drosophila. For example, unlike mammals, and many eukaryotic taxa, male flies do not recombine. The loss of recombination in one sex, although not the norm, has actually occurred many times in eukaryotes. In other insects, for example in Lepidopterans, or moths and butterflies, females don’t have recombination. - So why is a fundamental process that is seemingly essential and beneficial abolished in one of the sexes? This is one of the question I am also really interested in. The commonality between butterflies and flies, and many other examples, is that the heterogametic sex is the one losing recombination. The heterogametic sex is the sex with different sized chromosomes. In flies and us, humams, males have the different sex chromosomes, that is the X and Y. But in lepidopterans, females have different sex chromosomes that we call ZW but males have two Zs, instead, so we call this the ZW system. So, something is driving this repeated loss of recombination and it could be related to the sex chromosome configuration.
Was there a moment in your career that has determined your direction in research?
I don’t have an aha moment, and no inspiring story that has determined my academic interest. I went to places that I found very interesting and that dictated my next direction. It just progressively got more interesting and that set me on various paths and here I am now. I never had that aha moment or any pivotal event that drove and motivated me. I grew up I playing a lot of video games and had a very typical upbringing and I was not particularly outdoorsy. Not all of us need to have a path determined by particular life-altering events. For me, the love of science and my current interests stems from finding questions like how basic genetic processes work and how the genome is what it is inherently interesting. I will be ok if I never cure cancer or save the world – there are people better equipped to do that. I really believe in pursuing science for the sake of accruing knowledge Of course,it is incredibly important to care about research that can cure diseases and transform lives. But there is also so much value in being curious, and wanting to know for the sake of knowing.
What attracted you to UBC Zoology?
One, because I grew up here and this is home for me. Vancouver is a fantastic place to live. From the academic level, UBC is a very unique place for evolutionary biology research and for Drosophila research. There is an amazing combination of faculty in Zoology and the LSI doing fantastic work in Drosophila and world class evolutionary biologists. This makes UBC and Zoology a very unique place with a unique combination for me and I hope to take full advantage of both these strengths from UBC and Zoology.
Is there anything else about yourself that you would like us to know?
I like chatting about cool science even for things I don’t study. I love having conversations with people about exciting science. That means, I would love for people to just come chat with me. I’ve been told that I have a resting bitch face - please do not be put off by that. I am actually very approachable and would love to hear about everyone’s cool research.
