While an individual’s DNA profile doesn’t really change, its RNA profile is in constant flux as the body makes small, rapid adjustments to its own biology throughout the day and over the years. With the exception of some work on baboons, all large-scale vertebrate RNA profiling studies prior to this one had been performed only on animals in captivity. Furthermore, many used model organisms such as lab rats, which represent only a tiny fraction of vertebrate biodiversity, and may be quite genetically distinct from their feral cousins. Because of this, little is known about how animals adapt their day-to-day biology to the challenges of life in the wild.
In this study, researchers from UCLA and NPS ventured into the wild to collect RNA data from blood samples from 27 wild gray wolves living in Yellowstone National Park. Like DNA, RNA is a long molecule containing genetically encoded information that the cell uses to make proteins, the workhorses of the cell. The difference is that at a given time point, the cell is only using some of its genes (DNA), which it copies to make RNA, and RNAs are then used to make protein. Thus RNA gives us a snapshot of which genes were ‘on’ or ‘off’ in an individual at a particular moment. In science jargon, we refer to ‘on’ genes as being ‘expressed.’ RNA sequencing is a powerful new technology for capturing an individual’s RNA—or ‘gene expression’—profile.
For each wolf, researchers collected information regarding age, sex, mange infection status, and social rank (alpha or non-alpha). RNA sequencing found almost no genes whose expression was correlated with the latter factors, but found 625 genes associated with age! Surprised by this huge difference, the researchers looked to publicly available human expression data to corroborate their result. They took their pool of age-associated genes, and selected those genes that are shared between human and wolf. Then they asked whether each human gene was known to be associated with age. 60% of them were—that’s a lot of overlap!
Not only did the researchers find a ton of genes that correlate with age, they also found many were involved in a phenomenon known as ‘immunosenescence.’ This refers to the decreased ability of an aging immune system to adapt to new diseases. Even when the researchers corrected for the proportion of different types of blood cells in the samples, they still saw that a high proportion of age-sensitive genes were immunity-related.
This study was not without limitations, however. For one thing, the wolf genome is not completely available, so the RNA-seq data had to be analyzed using the dog genome. While this technique is perfectly acceptable for the field, it does introduce a bit of uncertainty into the final results. Additionally, since many biological factors correlate with age, it is very difficult to separate age from the influences of rank, sex, and disease, even when employing statistical methods as the authors do here. For example, stress related to rank or disease may influence the aging process in complex ways.
Limitations notwithstanding, this study gives us a glimpse of how life in the wild affects the broad strokes of gene expression. The findings regarding sex- and age-related gene expression are consistent with previous studies on primates, and provide further evidence that the latter is a major driver of gene expression change. In other words, of all the challenges wild wolves must adjust to, age may be the most biologically demanding.
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