Periodic Reporting for period 1 - FLEXGENOME (The Flexible Genome: understanding the genetic regulation of Phenotypic Plasticity.)
Reporting period: 2015-04-15 to 2017-04-14
Do our genes determine who we are? Or is the environment more important? In fact, many traits involved in behaviour, lifespan and disease are determined by how genes interact with the environment. This is called phenotypic plasticity: the ability of a single genome to express multiple phenotypes when exposed to different environments.
Plasticity is widespread and highly relevant in nature; it enhances reproduction and survival despite variation in e.g. temperature or food availability. Crucially, the genetic information needed to produce different phenotypes is encoded in a single genome, and environmental stimuli determine which phenotype is expressed. Unfortunately, how the genome achieves such flexibility is still largely a black box, and many important questions have remained unanswered. For example, what proportion of the genome is sensitive to the environment? Are there specialised genes for plasticity? How easily will plasticity evolve?
From a genetic point of view, plasticity presents a fundamental puzzle: how can different phenotypes be encoded in the same genome? Understanding this reveals how genetic programmes that translate genotypes to phenotypes are tuned to the environment, and how sensitivity of these programmes to the environment can be a source of phenotypic variation.
Many complex human medical conditions are influenced by gene-environment interactions. However, disentangling these interactions with epidemiological studies has its specific challenges. Instead, studying the genetics of phenotypic plasticity in animal models holds great promise for understanding mechanisms at the interface between genes and environment that also play a role in human disease, for example transcriptional regulation.
In light of current climate change, the lack of genetic knowledge on plasticity is particularly worrisome, as climate change is already having far-reaching effects on biodiversity, with knock-on effects on ecosystem services across the globe. Plasticity may facilitate a more rapid adaptation to changing climate regimes, or alternatively it may lead to maladaptive phenotype-environment mismatches that leave populations more vulnerable.
FLEXGENOME: studying how the environment regulates gene activity
FLEXGENOME studied the genetics of plasticity in the African butterfly Bicyclus anynana. It expresses two forms from the same genome as adaptation to its seasonal environment. During the wet season, butterflies reproduce rapidly and have short lifespans, while during the dry season they delay reproduction and live longer. Crucially, the same genome responds to the seasonal environment by producing different forms in each season.
Using state-of-the-art DNA sequencing technology, FLEXGENOME aimed to understand the genetic regulation of plasticity, and how it can evolve. The project had the following objectives:
1) to identify genetic programmes producing distinct, alternative phenotypes from a single genome in response to the environment
2) assess the potential for evolutionary change in plasticity by characterising genetic variation in these programmes.
I achieved these by analysing genome-wide genetic and expression variation in relation to environmental conditions.
FLEXGENOME was highly successful in generating a large amount of DNA sequencing data on the transcriptional regulation of phenotypic plasticity, which has significantly advanced understanding of this important phenomenon. The project identified thousands of genes involved in seasonal plasticity, representing a genome-wide plasticity programme. This allows the butterfly to express distinct life histories in each season, encompassing a broad and integrated suite of phenotypic traits including growth, hormone physiology, and reproductive strategy. Importantly, genetic variation for these programmes was highly depleted, likely as a result of purifying selection on plasticity that matches the predictable environment. Unfortunately, this depletion constrains the potential of this population to evolve in response to climate change, at least in the short term.
The strength of FLEXGENOME is combining an animal with well-studied natural ecology, with advanced genomic tools, in a powerful quantitative genetics experimental design across many samples. This combination of approaches across disciplines has allowed the analysis of the transcriptome as a highly dimensional plastic phenotype, disentangling how the genome and the environment interact to produce regulatory and phenotypic variation.
One important area of wider impact of FLEXGENOME is increased knowledge on biotic responses to climate change.
In order to assess how climate change scenarios will affect biodiversity loss it is crucial to predict which species will likely go extinct and which will adapt, but despite persistent debate we still lack empirical understanding of phenotypic plasticity’s role in aiding evolutionary adaptation to climate change. In many cases plasticity evolves as a specialized adaptation to predictable patterns of seasonality, where specific environmental cues accurately predict seasonal transitions.
The growing concern is that climatic change is expected to make cues less predictive for upcoming seasonal variation, inducing incorrect phenotypes. Resolving such maladaptive phenotype-environment mismatches crucially depends on the potential of plasticity to evolve.
Our data provide urgently needed empirical evidence on evolutionary potential, helping to clarify the role of plasticity in biotic climate change resilience.