The Mark Welch lab is developing a marine microinvertebrate as a new tool to investigate the molecular genetics of aging and senescence. Monogonont rotifers are small (~0.5mm) multicellular animals common in coastal waters around the world, and compose an important link between micro- and macro- trophic levels in these ecosystems. Monogononts are an attractive aging model for many reasons including their small size and ease of culturing, short lifespan (~3 weeks), allowing many replicate experiments to be conducted in a short time at low cost; the ability to maintain asexual clones, eliminating genetic variance between experiments; nearly a century of aging-related research centered on resource allocation and environmental effects on lifespan; and genomic resources developed at the Bay Paul Center, including complete transcriptomes and low-coverage genomes. In addition, many closely related species and strains of the Brachionus species group of salt-water monogononts respond differently to environmental stimuli that modulate aging (oxidants and antioxidants, food availability and nutritional content, etc.). This suggests that an approach combining comparative genomics, ecology, evolutionary theory, and systems biology could be used to elucidate subtle regulation of genetic pathways involved in aging that are missed in traditional mutation screens.

To initiate these studies we examined the transcriptional profile of the monogonont Brachionus manjavacas at five different life stages (eggs, pre-, early-, late-, and post-reproductive animals). We found significant changes in gene expression between each life stage, in particular an increase in the expression of more than 2000 genes involved in metabolism, cellular processes, or information processing during the early reproductive stage. We identified changes in the expression of genes implicated in major aging-related gene regulatory networks including the insulin signaling, TOR (Target of Rapamycin), JNK, and MAP kinase pathways, as well as changes in expression of a mitochondrial ADP-ribosyltransferase homologous to the human lifespan control gene SIRT4. Unexpectedly, we also discovered that multiple DNA damage response (DDR) pathways, including base excision, nucleotide excision, and mismatch repair, as well as homologous and non-homologous recombination, are upregulated in post-reproductive rotifers. This DDR response is accompanied by an increase in transcription of retrotransposons and an increase in the Argonaute protein PIWI, which is involved in the genomic defense against retrotransposons. Whether retro-element transposition is a cause or effect of DNA damage is not known, but the results suggest the utility of monogonont rotifers to study the relationship between aging and the accumulation of DNA damage.

Figure. Upper left: 100 rotifers were sampled from each of five life stages; images are of B. manjavacas at each stage, the oval objects are eggs. Lower left: number of genes with significant differential expression by KOG classification; significance was judged against an empirical Bayesian negative binomial distribution using baySeq. Right: Differential expression of genes involved in DDR; the heat map represents the range from low (blue) to high (red) expression for each of the five sampled life stages (columns) for each gene (rows).