Functionless DNA changes more rapidly, functional DNA more slowly. This is one of the fundamental principles of comparative genomics. It’s why people look at the ratio of synonymous nucleotide changes to nonsynonymous nucleotide changes within the coding sequence of genes. It’s why the exons of two related genes will still have strikingly similar sequences after the sequence of the introns have diverged to the point where it’s impossible to even detect homology. It’s also a way to identify which parts of the noncoding sequence surrounding a set of exons are functionally constrained. The bits of noncoding sequence that determine where, and when, and how much, a gene is expressed are by definition, functional, and should diverge more slowly between even related species than the big soup of functionless noncoding sequence that the functional bits of a genome float in. These conserved, functional, noncoding sequences are called, unimaginatively, conserved noncoding sequences (CNS).*
Comparison of a single syntenic orthologous gene pair in the genomes of peach and chocolate. Coding sequence marked in yellow, introns in gray, annotated UTRs in blue. Red boxes are regions of detectably similar sequence between the same genomic region in these two species. Taken from CoGePedia.
I’ve been playing with CNS since I first opened a command line window back as a first year grad student. The smallest CNS we’d consider “real” were 15 base pair exact matches between the same gene in two species. On the one hand, this seemed a bit too big, because I know lots of transcription factors bound to motifs as short as 6-10 base pairs long. On the other hand this seemed a bit too short because I’d see 15 base pair exact matches that couldn’t be real a bit too often (for example a match between a sequence in the intron of one gene, and the sequence after the 3′ UTR of another).
15 bp represented a compromise between the two concerns pushing in opposite directions. Then, in the fall of 2014, a computer science PhD student walked into my office and asked if I had any interesting bioinformatics problems he could work on. The result was a new algorithm (STAG-CNS) which was both more stringent at identifying conserved noncoding sequences and able identify shorter conserved sequences than was previously possible. It achieved both of these goals through the expedient of throwing genomes from more and more species at the problem.
When doing anything even vaguely related to quantitative genetics I would chose more missing data over more genotyping errors any day of the week. There are lots of approaches to making missing data less of a pain. The most straightforward of these is called imputation. Imputation essentially means using the genetic markers where you do have information to guess what the most likely genotypes would be at the markers where you don’t have any direct information on what the genotype is. This is possible because of a phenomenon known as linkage disequilibrium or “LD.” Both imputation and LD deserve their own entire write ups and they are on the list of potential topics for when I have another slow Sunday afternoon. For now the only thing you have to know about them is that, when information on a specific genetic marker is missing, it is often possible to guess with fairly high accuracy what that missing information SHOULD be. But when the information on a specific genetic marker is WRONG… well it’s usually a bit more of a mess (but I think the software solutions for this are getting better! Details at the end of the post.)
Figure 1: Genotype calls along chromosome 1 for six recombinant inbred lines (RILs).
Last night my major professor received the McClintock Prize in Maize Genetics.
His acceptance talk was really exciting and full of his newest ideas about the big problems of biology and evolution. However, looking back at his history, one of the amazing things about his career is that he’s reinvented himself entirely, switching from a research program focused on transposons and developmental biology to an entirely different career focused on taking the rigorous hypothesis development and hypothesis testing to the world of comparative plant genomics (and he started when there was exactly one sequenced plant genome, so being able to do comparative work at the time was quite something).
In many ways it makes me nostalgic for my time in the lab. In grad school you are essentially paid to think, while it often feels like as a faculty member you are paid mostly to attend meetings, fill out forms, and spend four hours a day answering e-mails. 😉
But this post isn’t about me. Congratulations Mike! Really is one of the fathers of modern maize genetics.
A partial sample of the 76 people who either received their PhDs or Postdoc’d in the Freeling Lab at UC Berkeley
Complete list of lab alumni here.
Corn is a weird plant in a lot of ways, but one we don’t think about very much (because it is so obvious) is that a corn plant has entirely separate male and female reproductive structures: tassels and ears respectively.* This isn’t unheard of in the plant kingdom, but in the particular group of grasses corn belongs to (the Andropogoneae) it’s quite remarkable. Tripsacums, the closest relatives of corn outside of corn’s own genus (Zea), have separate male and female flowers, but those flowers still share a common reproductive structure with the male flowers at the tip and the female flowers at the base. I’d like to have a photo of my own to show you, but I won’t until the Tripsacum plants growing in our greenhouse flower this summer, so in the meantime, go look at this great photo someone else took.
But I bring this up to point out that the segregation of male and female flowers into entirely different parts of the corn plant is still a relatively recent, and fragile, evolutionary development, and it doesn’t take a lot to disrupt it. There’s a series of tasselseed mutants.** Stresses can do it. Various infections can do it. And sometimes corn plants, particularly tillers, just decide to be confusing.
A maize (corn) tiller exhibiting the tasselseed phenotype which is often found in these secondary stalks
*And no, don’t call sorghum heads (or panicles, it depends on how formal you feel like being) tassels.
**Why aren’t there just as many anther ear mutants? It could have to do with the way corn flowers are wired. If female floral organs start developing, they actually cause the male floral organs to die prematurely. But anther ear phenotypes still happen.***
***QTL Controlling Masculinization of Ear Tips in a Maize (Zea mays L.) Intraspecific Cross
This will be on each poster from my group at the maize meeting
The maize genetics cooperation newsletter (MNL) dates all the way back to 1929. It was (and is) a way for members of the maize community to share interesting findings and preliminary data with their colleagues. Some of those results would ultimately turn into peer reviewed papers (a process that could take months or years) and others were just little weird pieces of data or observations which would otherwise have been lost as negative or ambiguous results. Here’s a good example of what a MNL note might look like.
That the maize genetics community has made the decision to be trusting and open with our hard earned data and analysis for almost 90 years, with nothing preventing others from taking advantage of this openness other than community norms, is a great example of the better angels of our collective nature. It’s a standard I drive myself to live up to.*
*Keeping in mind I probably don’t even qualify as a geneticist, let alone a maize geneticist.** But I am descended from maize geneticists, both genetically and academically.
**One of these days I really hope to clone my very own mutant.
My favorite figure.
The photo really says it all. In the first second your eye is immediately drawn to just how similar the two plants look. In the second, you start to wonder about the differences between the two (the sorghum plant is way more waxy, the corn plant has a purple auricle from anthocyanins).
I want to understand the conserved genomic features that maize corn and sorghum so similar, and the subtle genetic changes that make them so different.
Tomorrow I’m driving out to St. Louis for four back-to-back related meetings. Genomes to Fields, Corn Breeding, MaizeGDB, and Maize Genetics Conference.
For the 3rd year in a row the Maize Genetics Conference is going to operate under an “opt in” social media policy. Unless people explicitly opt in, attendees are forbidden from discussing talks or posters on social media (presumably this include blogs). Seven years ago, at my second maize genetics conference ever, I would have been in violation of this policy (if it had existed at the time) because I wrote these two posts. I know one of the authors well and he’s never expressed any concern over that post, and, while I’ve only met the second author in passing, I’m guessing she wasn’t bothered by my post since she cited it in her masters defense announcement.
In principle opt-in and opt-out should give identical results, but we know from a number of natural experiments that this is not the case, and that changing between these two can be used as a small nudge to produce socially desirable outcomes. (more…)
Which I suppose is not an unexpected development on the first day of classes for the fall semester. But it holds a special something this year. This semester for the first time as an actual assistant professor… I have to teach. First lecture tomorrow. Wish me luck, because I’m going to need as much of it as I can get.
My previous teaching experience was heavily weighted towards being a TA in multiple “science for non-majors” courses, which could have been a lot of fun. Unfortunately, each course had a reputation as an easy-A which attracted students who had absolutely no interest in the material.
Tomorrow should go a lot better than that. Much smaller class, specifically for the major, teaching material I developed myself. … fingers crossed….
It’s even smaller than mini-maize!
Developed by Xianmin Diao at CAAS and growing just outside of Beijing, China
And here are the wonderful group on researchers who work on Setaria italica (foxtail millet) at the Chinese Academy of Agricultural Sciences.
Just got back from a two week visit to China that let me catch up with a lot of old friends and collaborators as well as hopefully making a few important new connections.
Five cities (Shanghai, Tai’an, Wuhan, Chengdu, and CAAS) and seven presentations in fourteen days. And classes start on Monday.