In the course of updating my CV I've been checking what's become of hypotheses and projects we initiated but are no longer working on. The good news is that all of them are still active areas of research, and the ones I consider most important are getting increasing attention. Here's a quick overview of two of them.
1. Mutation rates in males vs females: In response to a paper reporting that point mutation rates are much higher in males than females (because sequences on X chromosomes evolve slower than sequences on Y chromosomes), I used a computer simulation model to show that the excess mutations in male lineages usually canceled out the benefits of sexual recombination for females (Redfield Nature 1994). This paper made a big media splash when it came out; Natalie Angier wrote it up for the New York Times, Jay Leno made a joke about it, and it even got a paragraph in Cosmopolitan! This was partly because the title was full of buzzwords 'sex', 'male', 'female', 'mutation', and partly because I wrote up a very clear useful press release.
It didn't make much of a scientific splash, and it hasn't had much impact on subsequent work on the evolution of sex, but the number of citations continues to increase. Many citations are from a European group of theoretical physicists who publish mainly in physics journals, but others are from evolutionary biologists. One 2007 review discusses the implications of my work, referring to it as 'a seminal study' (which I choose to interpret as not just a bad pun).
The hotspot paradox: Most meiotic crossing-over happens at chromosomal sites called recombination hotspots; the largest influence ont he activity of these sites is the DNA sequence at the site. While I was still a grad student I realized that, over evolutionary time, active hotspot sequences should disappear from genomes, being replaced first by leas-active and then by inactive sequences. This is because the mechanism by which hotspots cause recombination also causes more-active hotspot sequences to be physically replaced by less-active sequences. At that time the genetic evidence was strong but little was known about the molecular details. This creates a paradox, because hotspots have not disappeared (each chromosome has many of them).
About 10 years later I returned to this problem, using detailed computer simulations to model the evolution of hotspots. We first created a deterministic model of a single hotspot, and showed that none the forces opposing hotspot elimination (evolutionary benefits of recombination, benefits of correct chromosome segregation, direct fitness benefits of hotspots that also act as promoters, singly or in combination) were strong enough to maintain hotspots against their self-destructive activity. Several years later we created a better, stochastic, model that followed multiple hotspots on a chromosome - this confirmed and strengthened the previous conclusions.
The first paper (Boulton et al, PNAS 1997) was ignored by just about everyone, particularly the molecular biologists whose work might be expected to resolve the paradox. By the time the second paper was published (Pineda-Krch and Redfield 2005), evidence from human genetics had confirmed that the hotspot destruction originally studied in fungi also occurs in humans. Now, the increasing ability to examine individual crossover events at base-pair resolution has focused attention on the paradox, and most papers about hotspots in natural populations (including humans) mention it as a sign that the evolutionary history of recombination hotspots remains perplexing.
I'll write up a couple more of these projects tomorrow.
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