Project Summary
The eukaryotic innovation of genetic diversification through sex and recombination provides significant
adaptive advantages. Still, the recognition that some animals are capable of asexual reproduction dates back
to at least 1740 CE, and asexuality has arisen independently multiple times across the animal kingdom. This
transition is often accompanied by modified meiosis and genome organization. Since meiotic defects underlie
age-related decline in human fertility, and genomic instability is a hallmark of aging cells, studying how
successful asexual lineages can thrive in light of major modifications to these core cellular programs can
provide new molecular insights into the mechanisms of aging and infertility.
To characterize genomic signatures of asexual reproduction, we previously sequenced the genome and
transcriptome of Diploscapter pachys, a nematode from an unusually persistent asexual lineage estimated to
have originated 18 million years ago. This work showed that D. pachys lacks key meiotic genes and the first
(reductional) meiotic division, enabling reconstitution of a diploid genome in the oocyte without fertilization.
Strikingly, its nuclear genome is packaged into exactly one pair of chromosomes, which we showed derives
from the full fusion of all ancestral chromosomes. However, the genome assembly still contains many gaps
that limit our ability to answer key questions about D. pachys evolution: how and when genome fusions and
abridged meiosis arose, how a high level of sequence diversity is maintained without genetic recombination,
and which molecular changes drove the transition to asexual reproduction remain a mystery.
We propose to use the power of long-read sequencing and comparative genomics to address these questions.
In Aim 1, we will generate a highly contiguous, chromosome-level genome assembly for D. pachys. This will
reveal the pattern of ancestral chromosome fusions, whether major genome rearrangements likely preclude
meiotic crossovers, and the nature of chromosome fusion sites and telomeres. In Aim 2, we will produce
chromosome-level genome assemblies of four additional parthenogens and their closest known sexual relative
in the same phylogenetic clade. This will allow a comparative analyses of genome architecture and enable
evolutionary reconstruction of molecular genetic changes linked to asexual reproduction. In Aim 3, we will
analyze chromatin accessibility and changes in regulatory sequences and coding regions in all five species to
uncover whether genetic and/or epigenetic mechanisms underlie differences in expression levels between
alleles, as seen in D. pachys, which may enable these animals to overcome potentially high loads of
deleterious alleles. In summary, this study presents a unique opportunity to explore the evolution of asexual
reproduction in animals, a centuries-old mystery in biology, whose molecular underpinning may provide new
insights into molecular processes underlying aging in humans.