Primary Research Projects

1.) Effects of chromosomal inversions on gene flow between species.
2.) Plasticity and selection on recombination rate variation.
3.) What drives the spread of chromosomal inversions?
4.) Abundant lethal alleles in natural populations.
5.) Genetics and evolution education.

Effects of chromosomal inversions on gene flow between species

Species are defined as entities capable of "exchanging genes."  Understanding what causes or prevents gene exchange between groups is therefore fundamental to understanding the process of species formation ("speciation") and the origin of biodiversity on our planet. For over 17 years now, the Noor lab has pursued many projects Chromosome inversioninvestigating the effects of chromosomal inversions on gene exchange between hybridizing species for over a decade, particularly in Drosophila pseudoobscura and D. persimilis.  Specifically, if two species differ by one or more chromosomal inversions, large blocks of the genome cannot flow between species even when some of the hybrids are abstracts).  This decrease in gene flow appears to be directly related to the absence of crossing over that occurs within the inverted regions. Many lines of evidence support this conclusion-- e.g.,, when comparing two species, the inverted regions often show much higher divergence than non-inverted (colinear) regions, suggesting a lack of recombination and introgression.

However, exchange is not completely stopped in inversion heterozygotes. For instance, double-crossovers and noncrossover gene conversion should still allow for exchange between inversion types.  Nonetheless, inverted regions consistently show this higher divergence, implying little (if any) recombination and introgression. We have found that double-crossovers happen at far, far lower rates than expected in inverted regions, but they do happen. We've also obtained extensive whole-genome sequence (WGS) data from various intra- and inter-species crosses to examine rates of gene conversion in inversion heterozygotes to see how strong a barrier to gene exchange chromosomal inversions really are.

Additionally, we are collaborating with the research team of Prof. Carlos Machado to uninvert an inversion distinguishing D. pseudoobscura and D. persimilis, and then map factors inside the previously-inverted region associated with hybrid male sterility. It's been a "dream experiment" since inversions have prevented such mapping from being possible for almost 100 years, but current technology (e.g., CRISPR-Cas9 genome editing) makes it feasible at long last.

This work is fundamentally important to understanding why species persist as distinct entities even when they hybridize and the specific nature of how and how much chromosomal inversions may facilitate this process.

Plasticity and selection on recombination rate variation

Since 2006, our lab has pursued various projects examining the amount, genetic causes, and evolutionary consequences of recombination rate variation among regions of the Drosophila genome (see abstracts). Our past research identified that, contrary to earlier dogma, fine-scale variation in recombination does exist among regions of the Drosophila genome. We also found that this variation correlates strongly with amount of nucleotide diversity, and we found evidence this variation is related to the spread of advantageous alleles within species.

We previously only looked at variation AMONG STRAINS only briefly, and we only studied recombination rate in idealized laboratory conditions. We now extend our earlier work to answer the following specific questions. We are examining variation AMONG NATURAL POPULATIONS in recombination rate, and testing whether this variation may be adaptive.

Recombination rate is also plastic in response to environmental conditions. This sets up a situation wherein the recombination rates experienced under extreme conditions in nature may be maladaptive. We anticipate further testing for "plasticity compensation", wherein populations have adapted to mitigate detrimental environmentally induced recombination rates.

This last project is particularly important given effects of global climate change on our planet. Further, recombination is fundamental to many genetic and evolutionary processes, yet no studies have explored whether natural populations have adaptive differences in recombination rate, particularly in response to climatic conditions.

What drives the spread of chromosomal inversions?

Chromosomal inversions are often associated with either adaptation or species differences, but what causes these inversions to spread within a population? Kirkpatrick and Barton formalized a model in 2006 showing specific conditions under which the recombination-suppressing effects of an inversion can itself be adaptive, causing the inversion to spread to a high frequency. This process applies when adapting to two different environments involves the spread of alleles at two or more loci, and gene flow/ recombination between individuals in the two environments breaks apart these sets of alleles.

While popular, this model has not been subjected to a direct, experimental test, comparing it to alternatives.
Noor lab postdoc Kieran Samuk has written a successfully funded proposal to conduct such a test using experimental evolution in laboratory populations of Drosophila melanogaster. An inversi
on will be experimentally generated to capture a suite of alleles associated with adaptation to a particular food source, and the inversion will then be introduced into a captive population. Explicit predictions have been derived of the dynamics of this "new" inversion in the captive population, and we will observe how well the spread of the inversion matches these expectations.
This project will advance our understanding of the fundamental processes involved in the evolution of inversions and open the door to a variety of new studies on the role of structural variation in adaptation and speciation.

Abundant lethal alleles in natural populations

Natural selection removes bad alleles from natural populations, but counterintuitively, natural populations of
many species (including humans!) nonetheless still harbor numerous recessive "lethal" alleles. Classic studies in Drosophila found that 10%-40% of autosomes in natural populations had lethal of semi-lethal effects. WTH? This problem was examined heavily from the 1930's through the 1970's, with one camp arguing that such alleles may persist due to (direct or linkage-associated) advantages when heterozygous, while the other camp argued that this persistence merely reflected the balance between mutation and selection as well as the large number of potential mutations which could cause such lethality. By the late 1980's, much of the research community had accepted the latter argument.

Surely, the mutation-selection balance argument is largely correct and explains "most" of the lethal alleles that persist in natural populations. However, some lethal alleles are found at unusually high individual frequency. We are exploring this subset of abundant alleles to see if the other camp may have been correct for a small subset of variation. Fortunately, we have many more tools at our disposal than researchers did in the middle of the last century, including deficiency stocks, high-throughput sequencing, and population genetic tests for selection.
This research will help elucidate the forces affecting fitness-reducing variation that persists in natural populations of a wide range of species.

Genetics and evolution education

Our research team and collaborators have always been interested in biology education, including developing various new educational activities and resources. Two particularly unusual projects include developing a kit for studying natural selection in Drosophila marketed by Carolina Biological Supply and helping with the design of apps for learning about genetics and evolution. We continue to be interested in the development of such activities and resources, including doing proper assessment of their efficacy in classrooms.