Posted on July 5th 2020 by Carlo Pecoraro

1)      In your opinion, which are the most influential papers in adaptation genomics?

 

 

A: Work by Hopi Hoekstra’s lab on Peromyscus mice is an inspiration for all of us studying the genomic basis of adaptation. Two of my favourite are Linnen et al. 2013 (Science) on the genomic basis of coloration, and Weber et al. 2013 (Nature) on the genomic basis of burrowing behaviour. I find adaptive introgression particularly intriguing, and studies that actually demonstrate it are hard to come by. Norris et al. (2015; PNAS), Jones et al. (2018; Science), and Hsieh et al. (2019; Science) are three great studies on adaptive introgression in mosquitos, hares and humans, respectively.

 

Thinking about the interplay between selection and gene flow on the genomic architecture of traits, work by Sam Yeaman has been central in our review on the genomics of local adaptation with gene flow (Tigano and Friesen 2016; Molecular Ecology) and in developing my thinking about the role of structural variation in adaptation. And although centered on speciation, two must-read papers on the confounding effect of recombination and linked selection on the detection of loci under selection are by Burri et al. (2015; Genome Research) and Cruickshank and Hahn (2014; Molecular Ecology). I could go on for a while, but I’ll stop here.

 

 

C: This is a tricky question!! For an introduction to the field, there are several good reviews, among them, Stapley et al, 2010 in TREE, Hoban et al 2016 in American Naturalist, and of course, Anna’s one (Tigano & Freisen, 2016).

 

Yet, the field builds on ideas developed before genomics, and influential papers include the analysis of clines (from the work of Haldane in 1948 to recent papers like Bierne et al, 2011 in Molecular Ecology) and the concept of adaptation to heterogeneous environments (see for example the series of papers by Hedrick 1966,1996).

 

Personally, I’ve been much inspired by some papers like Lotterhos et al (2018) in Genome Biology about the modularity of genes involved in local adaptation to climate, Adrion et al (2015) in TREE about genomic clines in Drosophila or Therkildsen et al (2019) in Science about the genomic of rapid adaptation in response to fishing.

 

I also feel that now is an exciting time to study the genetic architecture of adaptation. We have an amazing knowledge of some adaptive genes, detected by genomic approaches and validated by experiments. One can see for instance the GEPHEbase (Courtier-Orgogozo et al, 2020, Nucleic Acid research). Moreover, I think that we are heading beyond identifying the genomic basis of adaptation when reading, for instance, Yeaman et al (2018) in PLOSGenetics developing a framework to test if adaptation is repeatable or Lee & Coop (2019) in Philosophical Transactions of the Royal Society, discussing convergent adaptation.

 

 

 

 

2)      How did you first start working on this topic?

 

 

A: Studying adaptation meant to combine my interests in ecology, evolution and conservation. I wanted (and still trying) to understand the ecological factors populations and species are adapted to, how these adaptations evolved, and what’s the potential of species to adapt to changes in their environment, particularly climate change. I started to address these questions in arctic seabirds for my PhD, and expanded to other taxa later, but I’m still driven by the same fundamental questions.

 

 

C: During my PhD, I mostly studied adaptation by mimicry and speciation through phenotypic and ecological approaches, which raised the question of “what is the genetic basis of all that?”! So I turned to genomics to address the genetic architecture of adaptation first through QTL analysis, and second, with population genomic data.

 

 

 

 

3)      Could you please describe your current “adaptation genomics” projects?

 

 

A: Currently, I’m working on the factors, including genome structure and chromosomal rearrangements, contributing to an adaptive radiation in Peromyscus mice, with a focus on adaptations to desert in the cactus mouse (P. eremicus). I’m also continuing my work on the genomic basis of an adaptive dimorphism, a copy number variant, in the common murre (Uria aalge) using linked-reads and long reads, and finalizing previous work on the link between diversity, differentiation and chromosomal inversions in a fish, the Atlantic silverside (Menidia menidia).

 

 

C: I am presently working on chromosomal inversions in a seaweed fly and trying to understand the importance of such structural rearrangements for adaptation to heterogeneous environments. I am using a large sampling across North America of > 1,500 flies that we sequenced using low-coverage whole-genome sequencing. I am also more and more involved in collaborative projects looking for the link between structural variants (fusions, duplications, inversions…) and adaptation.

 

 

 

 

4)      Long-read sequencing is a game-changer: how is it impacting this field?

 

 

A: First thing it comes to mind is ‘characterization of structural variants’. Structural variants are often complex and/or associated with repeats, which make their assembly and characterization hard or impossible with short reads. Long reads help a lot with that. Then ‘genome assemblies’, especially of highly repetitive genomes. It is evident that long reads are useful to ‘study repeats’ on and by itself! Once thought to be irrelevant ‘junk DNA’, repetitive DNA is implicated in all sort of evolutionary processes, from adaptation to the evolution of structural variants, and long reads are contributing to a better understanding of their role.

 

 

C: Long-read sequencing is right now one of the best helpers for people working on non-model species! Amazingly it allows assembling high-quality genomes for almost any species, which, in turn, makes all analysis much easier and more meaningful. By working on structural variants, and particularly on large rearrangements, I can tell you how a good reference genome is super important!

 

It will also allow us to better characterize structural variation across individuals when prices will allow to easily sequence many samples. Or perhaps by having few well-sequenced individuals as a reference and many sequenced at shallow coverage? In-house libraries and adjusted local nanopore sequencing are so promising to help including structural variants (and not only SNPs) in population genomics and adaptation genomics.

 

 

 

5)      In your opinion, which are the next big challenges in the study of adaptations?

 

 

A: We are finding more and more how patterns of molecular variation across the genome affect our ability to identify the loci underpinning adaptations. Although this is an active field of research, we still need to get a better understanding of the factors affecting our ability to detect signatures of selection, such as recombination and genome structure for example. Critical to this point, the challenge, or maybe the dream, would then be to be able to apply the methods that are developed and used for ‘model species’ to validate candidate loci for adaptive traits in a wider variety of organisms. We know so much about a limited number of species, but very little to nothing on most of the remaining. Finally, the study of adaptation would hugely benefit from a greater integration of disciplines, such as, but not limited to, molecular and cellular biology, physiology, ecology, biomechanics, physics, etc. There is much more to the study of adaptation than finding the locus associated with a trait of interest, although this is very interesting too!

 

 

C: As sequencing and computer analyses become easier, the same challenge will remain to access relevant natural variation in our study organism. Sampling relevant populations, accurately describe the ecological conditions, quantifying complex phenotypes, and perhaps more importantly, have a good knowledge of the natural history of the species, will remain critical to fully understand adaptation. 

 

On the genomic front, there has been much debate about the matter of accounting for demography or spatial correlation to tell apart neutral from adaptative variation but I feel that this has received some answers, or at least, this is a challenge that we are aware of. What is emerging though, is the matter of genomic heterogeneity, and how to account for recombination when scanning for adaptation.