Next Steps for Functional Genomics Proceedings of a Workshop (2020) / Chapter Skim
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5 Advancing Research on the Environmental Regulation of Gene Function
5 Advancing Research on the Environmental Regulation of Gene Function
Pages 53-74
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From page 53... ...
Sarah Kocher of Princeton University described how the environment shapes social behavior in sweat bees, some of whom create highly organized societies like those of honeybees, while others are solitary. Joanna Kelley of Washington State University described how certain small fish have adapted to live in water that is highly sulfidic.
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From page 54... ...
Social insects, such as ants and honeybees, are excellent organisms in which to study social behavior because they are extreme examples of social living and have been helpful in understanding the molecular mechanisms behind social behaviors, such as caste differentiation. Using social insects, researchers who are interested in understanding what facilitates the transition between solitary and social living must work in systems that include closely related species of both highly social animals and animals that are solitary or only weakly social.
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From page 55... ...
A quantitative polymerase chain reaction (qPCR) showed that social bees have higher expression levels of syntaxin 1A in their brains than solitary bees.
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From page 56... ...
In particular, working with postdocs Ben Rubin and Beryl Jones, Kocher's group has been carrying out comparative genomics on a collection of 19 different species of sweat bees, including L albipes, in an effort to identify the genetic mechanisms shaping variation in their social behavior.
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From page 57... ...
They tested for relaxed selection on each of the branches that represent losses of social behavior and compared those results with species that are eusocial and have maintained that behavior. This comparison identified 443 genes with relaxed selection associated with the loss of eusociality, Kocher said, and those genes were enriched for things such as chromosome condensation and DNA packaging, indicating an important role in chromatin accessibility.
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From page 58... ...
. When her team examined the proportion of transcription factor binding sites associated with either solitary or social genomes across the 19 different species, they found three times as many binding sites positively correlated with social genomes as binding sites associated with solitary genomes.
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From page 59... ...
HOW ENVIRONMENTAL FACTORS INFLUENCE A COMPLEX PHENOTYPE In the next presentation, Joanna Kelley discussed how variation in natural systems can be used to understand complex phenotypes. She began by sketching out the usual frame for understanding the gene–phenotype connection: genetic variation leads to differences in gene expression and in protein abundance, which affect biochemical and physiological function, and, ultimately, the function of an organism and its fitness.
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From page 60... ...
The two environments are very close to one another -- within about 200 meters. "So," Kelley said, "we're going to leverage this comparative contrast with having multiple different species in exactly the same environment to see how that phenotype of survival in hydrogen sulfide arises and connects to underlying genetic variation." The three species that she studied are widely distributed across the large phylogeny of Poeciliidae.
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From page 61... ...
Because most of her group's experiments had been conducted on wildcaught individuals, it was impossible to tell whether the increased expression of certain genes in the sulfidic populations was because of evolved changes or whether these were responses to the fish being in water with high levels of H2S. To determine which differences in gene expression between ecotypes were due to adaptation and which were due to plasticity, Kelley and her collaborators carried out a common garden experiment in which one of the species was brought into the lab where several generations were raised and then exposed to H2S.
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From page 62... ...
" The answers are not obvious, she said, but the question should be asked. ENVIRONMENTAL REGULATION OF GENE FUNCTION IN AGRICULTURE Moving from the first two presentations, which focused on insects and fish living in natural environments, Nathan Springer of the University of Minnesota spoke about crop plants, which have been carefully bred for optimized performance in farm fields.
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From page 63... ...
• How do we effectively link genomic variation to GxE effects? Concerning differential gene expression, Springer said that like many of the previous speakers, he had studied how gene expression varies between closely related species or even between different individuals in a single species, and that he agreed with most of what had been said at the workshop.
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From page 64... ...
"I'm going to tell you about why this has been difficult, and why I think we're getting closer," he said. For a decade or so, Springer said, corn researchers had a single reference genome, but within the past couple of years that has grown to about 40 fairly high-quality reference genomes, and that has revealed a great deal of additional complexity that must be taken into account.
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From page 65... ...
"So we're throwing away data right now that we should be gathering and keeping forever." ENVIRONMENTAL FACTORS AFFECTING QUANTITATIVE TRAITS IN DROSOPHILA Next, Trudy Mackay of Clemson University spoke about how environmental factors affect quantitative traits in Drosophila. Quantitative traits, she explained, are continuously distributed in natural populations and include such things as height, weight, and blood pressure.
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From page 66... ...
After collecting these data, Mackay and her team analyzed them to uncover the effects of genotype, environment, sex, and interactions among the three factors on the lifespans of the flies. They found clear genetic variation within each temperature -- some lines survived significantly longer than other lines -- as well as sexual dimorphism and phenotypic plasticity (Huang et al., 2020)
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From page 67... ...
FIGURE 5-3 Display of variation in quantitative traits due to the environment (top) and sex (bottom)
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From page 68... ...
. They found that much of the transcriptome was highly sexually dimorphic and that there was enormous genetic variation and sexual dimorphism at the level of transcription -- echoing what they had seen at the level of quantitative traits.
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From page 69... ...
project, she said. "I think there would be great value in actually doing a similar large community-based project with genetic variation overlaid." Sex Differences in Comparative Functional Genomics Sex differences should be front and center in comparative functional genomics research.
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Are sex biases in gene expression conserved between humans and other mammals used in basic research and in pharmaceutical trials? And do sex differences in gene expression across the genome contribute to sex differences in a trait?
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From page 71... ...
"It's not invariably true," Page said, "but there was a tendency." When his team summed the effects on height across the hundreds of implicated genes, they found that the result of the differences in expression explained 12 percent of the observed difference in the average heights between females and males. The next steps, Page said, will be to collect data from more tissues, more cell types, more developmental stages, and more species, and to explore whether sex biases in gene expression explain sex differences in traits other than height.
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From page 72... ...
DISCUSSION The session moderator, Philip Benfey, opened the discussion by referring to the keynote talk by Aviv Regev, who had suggested that researchers in functional genomics think "in terms of a random sampling across a large data population versus a more defined factorial approach," as Benfey phrased it. He asked the panelists which approach would be most effective in their experimental systems.
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From page 73... ...
Mackay responded that the sort of complexity that Churchill and others were describing is only going to be understood "when we can stop going from one variant to one transcript and to one trait, and start using our data to infer transcriptional genetic networks based on naturally occurring genetic variation and how those entire regulatory networks translate to organismal phenotypes." With enough data, she said, it should be possible to map expression quantitative trait loci (eQTLs) that have cis effects, eQTLs that have trans effects, figure out which eQTLs have both, and then start to infer a cis–trans-regulatory network.
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