Abstract
The genomic basis of ageing still remains unknown despite being a topic of study for many years. Here, we present data from 20 experimentally evolved laboratory populations of Drosophila melanogaster that have undergone two different life-history selection regimes. One set of ten populations demonstrates early ageing whereas the other set of ten populations shows postponed ageing. Additionally, both types of populations consist of five long standing populations and five recently derived populations. Our primary goal was to determine which genes exhibit changes in expression levels by comparing the female transcriptome of the two population sets at two different time points. Using three different sets of increasingly restrictive criteria, we found that 2.1–15.7% (82–629 genes) of the expressed genes are associated with differential ageing between population sets. Conversely, a comparison of recently derived populations to long-standing populations reveals little to no transcriptome differentiation, suggesting that the recent selection regime has had a larger impact on the transcriptome than its more distant evolutionary history. In addition, we found very little evidence for significant enrichment for functional attributes regardless of the set of criteria used. Relative to previous ageing studies, we find little overlap with other lists of aging related genes. The disparity between our results and previously published results is likely due to the high replication used in this study coupled with our use of highly differentiated populations. Our results reinforce the notion that the use of genomic, transcriptomic, and phenotypic data to uncover the genetic basis of a complex trait like ageing can benefit from experimental designs that use highly replicated, experimentally-evolved populations.
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Acknowledgements
We thank Bryan Clifton for technical help and to the University of California, Irvine High-Performance Computing cluster for facilitating our analyses. This work was supported by a FRT UCI award to J.M.R. and, in part, through access to the Genomics High Throughput Facility Shared Resource of the Cancer Center Support Grant (P30CA-062203) at the University of California, Irvine and NIH shared instrumentation grants 1S10RR025496-01, 1S10OD010794-01, and 1S10OD021718-01 and from funds provided by the UCI School of Biological Sciences.
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10522_2019_9823_MOESM1_ESM.tiff
Supplementary material 1—Timeline of the generation of the experimentally evolved populations of D. melanogaster used. Any terminal arrow denotes five populations. In parenthesis, number of generations elapsed of separated evolution for a particular subset of populations. All evolved populations analyzed derive ultimately from an outbred population, named IV, collected at South Amherst, MA (Rose 1984). More recently, all evolved populations are derived from an ancestral treatment “O”, which is characterized by a generation length of 70 days. Initially, the “CO” populations were derived from the “O” populations by following the C-type selection regime, which entailed a 28-day generation length. From the “CO” lines, the “ACO” populations were generated by applying the A-type selection regime of accelerated development, shortening the generation length to 10 days. Lastly, the “NCO” and “AO” treatments derived from the original “O” populations undergoing again the mentioned C-type and A-type selection regimes, respectively. (TIFF 177 kb)
10522_2019_9823_MOESM2_ESM.eps
Supplementary material 2—Principle component analysis (PCA) plots. PCA was done for 14- and 21-day time points (left and right, respectively) using normalized RNA-seq count data for ten early reproducing populations (five ACO and five AO) and ten late reproducing populations (five CO and five nCO). The proportion of variance explained by each component is indicated. For both time points, the grouping of the populations recapitulates the type of selection regime to which they were exposed. (EPS 18 kb)
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Supplementary material 3—Correlation matrices among expression levels across populations. Correlation matrices were generated for 14- and 21-day time points (left and right, respectively) using normalized RNA-seq count data from each population. For both time points, the clustering of the populations precisely segregates to which of the two selection regimes the populations were individually exposed. Equivalent randomized expression data (per gene across populations) yielded no equivalent perfect segregation of populations based on their association with a particular treatment (P<0.001; 1000 randomized datasets). The average correlations values were 0.986 and 0.987 at day 14, and 0.986 and 0.987 at day 21, for the A- and C-population types, respectively. The identity of each population is shown on the right and at the bottom of each chart. (EPS 3037 kb)
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Barter, T.T., Greenspan, Z.S., Phillips, M.A. et al. Drosophila transcriptomics with and without ageing. Biogerontology 20, 699–710 (2019). https://doi.org/10.1007/s10522-019-09823-4
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DOI: https://doi.org/10.1007/s10522-019-09823-4