Research

I am an evolutionary and computational biologist, broadly interested in questions of genome evolution, mutation rate variation, and the consequences population history. I use high performance computing, statistics, simulations, and comparative genomics to study questions relating to sex-biased mutational processes including, how sex chromosomes arise and evolve, why mutation rates differ between males and females, and how expression patterns vary between the sexes. I work with collaborators to develop models and analyze experimental data to understand the effects of natural selection, convergent evolution, tumor progression and maternal-fetal conflict.

Details about specific projects:

1. Assessing the magnitude and effects of male mutation bias

 

If most mutations result from errors during replication (during germline cell divisions), then differences in the rounds of germline cell divisions between males and females are expected to result in more mutations introduced from one parent or the other. In mammals, the male germline undergoes many more rounds of division than the female germline, and this is observed in a resulting "male mutation bias", where more mutations are introduced from the male versus the female germline. I am interested in learning how this process occurs, and what its genomic impacts are. With Kateryna Makova.
Read more here: Genome analyses substantiate male mutation bias in many species

I am also interested in learning what associations exist between variations in life history traits and molecular evolution, especially male mutation bias. With Chris VendittiMark Pagel, and Kateryna Makova.
Read more here: Do variations in substitution rates and male mutation bias correlate with life-history traits? A study of 32 mammalian genomes



2. Understanding the evolution of sex chromosomes

Diversity on the human Y chromosome is significantly reduced relative to neutral expectations. We are investigating the possible causes of this reduction. With Kirk Lohmueller and Rasmus Nielsen. Read more here: Natural selection reduced diversity on human Y chromosomes

The human X and Y chromosomes evolved from a pair of homologous autosomes, but today the X has more than ten times the gene content of the Y. Which genes were lost, and how does the loss of functional genes on the Y affect the evolution of the human X? Are genes with some functions or expression patterns more likely to be retained on the Y? With Kateryna Makova.
Read more here: Gene Survival and Death on the Human Y Chromosome

There is a set of genes on the sex chromosomes of eutherian mammals (e.g., human, mouse, dog - basically all mammals except marsupials and monotremes) that are on the non-sex chromosomes (autosomes) in marsupials. We can compare the genomic and expression evolution of the X- and Y-linked gametologs with their homologs on the autosomes to learn how X- and Y-linkage affect molecular evolution. With Kateryna Makova.
Read more here: Evolution and survival on eutherian sex chromosomes

The ability to sequence whole genomes has allowed for amazing advances in understanding the evolution of sex chromosomes across species. With Kateryna Makova. Read more here: Genomic analyses of sex chromosome evolution

 



3. Determining the effects of recombination suppression on the sex chromosomes in mammals


 

In species with heteromorphic sex chromosomes, inversions, or other events, often accumulate to suppress recombination so that sexually antagonistic alleles won't adversely affect the opposite sex. We aim to understand how these recombination suppression events occur, and what their genomic signatures are. With Ravi Shanker Pandey and Rajeev Azad.
Publication recently accepted.

Whereas the non-sex chromosomes (autosomes) can partner up and swap DNA over their entire lengths, the sex chromosomes, X and Y, in mammals only swap DNA on the tips. We are studying how the inhibition of swapping (the suppression of recombination) affects patterns of diversity across the human X chromosome.
With Logan Curtis-Whitchurch and Rasmus Nielsen



4. Applying RNAseq to understand human biology

We are working on methods to correct for technical errors when assessing allele-specific expression in RNAseq data. With Line Skotte and Rasmus Nielsen.

The autoimmune disease Rheumatoid Arthritis (RA) affects 1% of the population, occurring three-times more often in females than in males. Curiously, however, the symptoms of RA disappear in approximately 50% of female RA patients during pregnancy. By assessing disease activity and gene expression using RNAseq before, during and after pregnancy, collaborating across multiple labs and countries, we hope to gain insight into how genes and environment interact to facilitate disease amelioration. With Kellie Ottoboni, Damini Jawaheer and Rasmus Nielsen