Assessing rapid evolution in a changing environment

Climate change poses a serious threat to species persistence. Effective modelling of evolutionary responses to rapid climate change is therefore essential. In this review we examine recent advances in phylogenetic comparative methods, techniques normally used to study adaptation over long periods, which allow them to be applied to the study of adaptation over shorter time scales. This increased applicability is largely due to the emergence of more flexible models of character evolution and the parallel development of molecular technologies that can be used to assess adaptive variation at loci scattered across the genome. The merging of phylogenetic and population genetic approaches to the study of adaptation has significant potential to advance our understanding of rapid responses to environmental change.     

The molecular genetic basis of plant adaptation

How natural selection on adaptive traits is filtered to the genetic level remains largely unknown. Theory and quantitative trait locus (QTL) mapping have provided insights into the number and effect of genes underlying adaptations, but these results have been hampered by questions of applicability to real biological systems and poor resolution, respectively. Advances in molecular technologies have expedited the cloning of adaptive genes through both forward and reverse genetic approaches. Forward approaches start with adaptive traits and attempt to characterize their underlying genetic architectures through linkage disequilibrium mapping, QTL mapping, and other methods. Reverse screens search large sequence data sets for genes that possess the signature of selection. Though both approaches have been successful in identifying adaptive genes in plants, very few, if any, of these adaptations' molecular bases have been fully resolved. The continued isolation of plant adaptive genes will lead to a more comprehensive understanding of natural selection's effect on genes and genomes.     

Common garden experiments in the genomic era: new perspectives and opportunities

The study of local adaptation is rendered difficult by many evolutionary confounding phenomena (for example, genetic drift and demographic history). When complex traits are involved in local adaptation, phenomena such as phenotypic plasticity further hamper evolutionary biologists to study the complex relationships between phenotype, genotype and environment. In this perspective paper, we suggest that the common garden experiment, specifically designed to deal with phenotypic plasticity, has a clear role to play in the study of local adaptation, even (if not specifically) in the genomic era. After a quick review of some high-throughput genotyping protocols relevant in the context of a common garden, we explore how to improve common garden analyses with dense marker panel data and recent statistical methods. We then show how combining approaches from population genomics and genome-wide association studies with the settings of a common garden can yield to a very efficient, thorough and integrative study of local adaptation. Especially, evidence from genomic (for example, genome scan) and phenotypic origins constitute independent insights into the possibility of local adaptation scenarios, and genome-wide association studies in the context of a common garden experiment allow to decipher the genetic bases of adaptive traits.     

Molecular footprints of inshore aquatic adaptation in Indo-Pacific humpback dolphin (Sousa chinensis)

The Indo-Pacific humpback dolphin, Sousa chinensis, being a member of cetaceans, had fully adapted to inshore waters. As a threatened marine mammal, little molecular information available for understanding the genetic basis of ecological adaptation. We firstly sequenced and obtained the draft genome map of S. chinensis. Phylogenetic analysis in this study, based on the single copy orthologous genes of the draft genome, is consistent with traditional phylogenetic classification. The comparative genomic analysis indicated that S. chinensis had 494 species-specific gene families, which involved immune, DNA repair and sensory systems associated with the potential adaption mechanism. We also identified the expansion and positive selection genes in S. chinensis lineage to investigate the potential adaptation mechanism. Our study provided the potential insight into the molecular bases of ecological adaptation in Indo-Pacific humpback dolphin and will be also valuable for future understanding the ecological adaptation and evolution of cetaceans at the genomic level.     

Genomic insights into adaptation to high-altitude environments

Elucidating the molecular genetic basis of adaptive traits is a central goal of evolutionary genetics. The cold, hypoxic conditions of high-altitude habitats impose severe metabolic demands on endothermic vertebrates, and understanding how high-altitude endotherms cope with the combined effects of hypoxia and cold can provide important insights into the process of adaptive evolution. The physiological responses to high-altitude stress have been the subject of over a century of research, and recent advances in genomic technologies have opened up exciting opportunities to explore the molecular genetic basis of adaptive physiological traits. Here, we review recent literature on the use of genomic approaches to study adaptation to high-altitude hypoxia in terrestrial vertebrates, and explore opportunities provided by newly developed technologies to address unanswered questions in high-altitude adaptation at a genomic scale.     

Analysis of new retrogenes provides insight into dog adaptive evolution

The origin and subsequent evolution of new genes have been considered as an important source of genetic and phenotypic diversity in organisms. Dog breeds show great phenotypic diversity for morphological, physiological, and behavioral traits. However, the contributions of newly originated retrogenes, which provide important genetic bases for dog species differentiation and adaptive traits, are largely unknown. Here, we analyzed the dog genome to identify new RNA‐based duplications and comprehensively investigated their origin, evolution, functions in adaptive traits, and gene movement processes. First, we totally identified 3,025 retrocopies including 476 intact retrogenes, 2,518 retropseudogenes, and 31 chimerical retrogenes. Second, selective pressure along with ESTs expression analysis showed that most of the intact retrogenes were significantly under stronger purifying selection and subjected to more functional constraints when compared to retropseudogenes. Furthermore, a large number of retrocopies and chimerical retrogenes that occurred approximately 22 million years ago implied a burst of retrotransposition in the dog genome after the divergence time between dog and its closely related species red fox. Interestingly, GO and pathway analyses showed that new retrogenes had expanded in glutathione biosynthetic/metabolic process which likely provided important genetic basis for dogs' adaptation to scavenge human waste dumps. Finally, consistent with the results in human and mouse, a significant excess of functional retrogenes movement on and off the X chromosome in the dog confirmed a general pattern of gene movement process in mammals which was likely driven by natural selection or sexual antagonism. Together, these results increase our understanding that new retrogenes can reshape the dog genome and provide further exploration of the molecular mechanisms underlying the dogs' adaptive evolution.     

Source-sink dynamics of virulence evolution

To understand the evolution of genetic diversity within species--bacterial and others--we must dissect the first steps of genetic adaptation to novel habitats, particularly habitats that are suboptimal for sustained growth where there is strong selection for adaptive changes. Here, we present the view that bacterial human pathogens represent an excellent model for understanding the molecular mechanisms of the adaptation of a species to alternative habitats. In particular, bacterial pathogens allow us to develop analytical methods to detect genetic adaptation using an evolutionary 'source-sink' model, with which the evolution of bacterial pathogens can be seen from the angle of continuous switching between permanent (source) and transient (sink) habitats. The source-sink model provides a conceptual framework for understanding the population dynamics and molecular mechanisms of virulence evolution.     

Molecular genetic mapping and plant evolutionary biology

With the advent of molecular genetic mapping, it is possible to study the genetic basis of natural heritable variation in new ways. Here, three potential uses of molecular genetic mapping in plant ecology and evolutionary biology are discussed; (1) accurate estimation of genetic parameters, (2) understanding speciation and/or adaptation, and (3) investigating whole genome organization. Basic methods for mapping genes and important mapping strategies are outlined. Recent studies are introduced to illustrate progress so far in applying the new methods in ecological and evolutionary research.     

Differential trends in the codon usage patterns in HIV-1 genes

Host-pathogen interactions underlie one of the most complex evolutionary phenomena resulting in continual adaptive genetic changes, where pathogens exploit the host's molecular resources for growth and survival, while hosts try to eliminate the pathogen. Deciphering the molecular basis of host-pathogen interactions is useful in understanding the factors governing pathogen evolution and disease propagation. In host-pathogen context, a balance between mutation, selection, and genetic drift is known to maintain codon bias in both organisms. Studies revealing determinants of the bias and its dynamics are central to the understanding of host-pathogen evolution. We considered the Human Immunodeficiency Virus (HIV) type 1 and its human host to search for evolutionary signatures in the viral genome. Positive selection is known to dominate intra-host evolution of HIV-1, whereas high genetic variability underlies the belief that neutral processes drive inter-host differences. In this study, we analyze the codon usage patterns of HIV-1 genomes across all subtypes and clades sequenced over a period of 23 years. We show presence of unique temporal correlations in the codon bias of three HIV-1 genes illustrating differential adaptation of the HIV-1 genes towards the host preferred codons. Our results point towards gene-specific translational selection to be an important force driving the evolution of HIV-1 at the population level.     

Genome‐wide signatures of flowering adaptation to climate temperature: Regional analyses in a highly diverse native range of Arabidopsis thaliana

Current global change is fueling an interest to understand the genetic and molecular mechanisms of plant adaptation to climate. In particular, altered flowering time is a common strategy for escape from unfavourable climate temperature. In order to determine the genomic bases underlying flowering time adaptation to this climatic factor, we have systematically analysed a collection of 174 highly diverse Arabidopsis thaliana accessions from the Iberian Peninsula. Analyses of 1.88 million single nucleotide polymorphisms provide evidence for a spatially heterogeneous contribution of demographic and adaptive processes to geographic patterns of genetic variation. Mountains appear to be allele dispersal barriers, whereas the relationship between flowering time and temperature depended on the precise temperature range. Environmental genome‐wide associations supported an overall genome adaptation to temperature, with 9.4% of the genes showing significant associations. Furthermore, phenotypic genome‐wide associations provided a catalogue of candidate genes underlying flowering time variation. Finally, comparison of environmental and phenotypic genome‐wide associations identified known (Twin Sister of FT, FRIGIDA‐like 1, and Casein Kinase II Beta chain 1) and new (Epithiospecifer Modifier 1 and Voltage‐Dependent Anion Channel 5) genes as candidates for adaptation to climate temperature by altered flowering time. Thus, this regional collection provides an excellent resource to address the spatial complexity of climate adaptation in annual plants.     

Gene copy number variations in adaptive evolution: The genomic distribution of gene copy number variations revealed by genetic mapping and their adaptive role in an undomesticated species,white spruce (Picea glauca)

Gene copy number variation (CNV) has been associated with phenotypic variability in animals and plants, but a genomewide understanding of their impacts on phenotypes is largely restricted to human and agricultural systems. As such, CNVs have rarely been considered in investigations of the genomic architecture of adaptation in wild species. Here, we report on the genetic mapping of gene CNVs in white spruce, which lacks a contiguous assembly of its large genome (~20 Gb), and their relationships with adaptive phenotypic variation. We detected 3,911 gene CNVs including de novo structural variations using comparative genome hybridization on arrays (aCGH) in a large progeny set. We inferred the heterozygosity at CNV loci within parents by comparing haploid and diploid tissues and genetically mapped 82 gene CNVs. Our analysis showed that CNVs were distributed over 10 linkage groups and identified four CNV hotspots that we predict to occur in other species of the Pinaceae. Significant relationships were found between 29 of the gene CNVs and adaptive traits based on regression analyses with timings of bud set and bud flush, and height growth, suggesting a role for CNVs in climate adaptation. The importance of CNVs in adaptive evolution of white spruce was also indicated by functional gene annotations and the clustering of 31% of the mapped adaptive gene CNVs in CNV hotspots. Taken together, these results illustrate the feasibility of studying CNVs in undomesticated species and represent a major step towards a better understanding of the roles of CNVs in adaptive evolution.     

Linking genotypes to phenotypes and fitness: how mechanistic biology can inform molecular ecology

The accessibility of new genomic resources, high‐throughput molecular technologies and analytical approaches such as genome scans have made finding genes contributing to fitness variation in natural populations an increasingly feasible task. Once candidate genes are identified, we argue that it is necessary to take a mechanistic approach and work up through the levels of biological organization to fully understand the impacts of genetic variation at these candidate genes. We demonstrate how this approach provides testable hypotheses about the causal links among levels of biological organization, and assists in designing relevant experiments to test the effects of genetic variation on phenotype, whole‐organism performance capabilities and fitness. We review some of the research programs that have incorporated mechanistic approaches when examining naturally occurring genetic and phenotypic variation and use these examples to highlight the value of developing a comprehensive understanding of the relationship between genotype and fitness. We give suggestions to guide future research aimed at uncovering and understanding the genetic basis of adaptation and argue that further integration of mechanistic approaches will help molecular ecologists better understand the evolution of natural populations.     

INTEGRATING EVOLUTIONARY AND FUNCTIONAL APPROACHES TO INFER ADAPTATION AT SPECIFIC LOCI

Inferences about adaptation at specific loci are often exclusively based on the static analysis of DNA sequence variation. Ideally, population‐genetic evidence for positive selection serves as a stepping‐off point for experimental studies to elucidate the functional significance of the putatively adaptive variation. We argue that inferences about adaptation at specific loci are best achieved by integrating the indirect, retrospective insights provided by population‐genetic analyses with the more direct, mechanistic insights provided by functional experiments. Integrative studies of adaptive genetic variation may sometimes be motivated by experimental insights into molecular function, which then provide the impetus to perform population genetic tests to evaluate whether the functional variation is of adaptive significance. In other cases, studies may be initiated by genome scans of DNA variation to identify candidate loci for recent adaptation. Results of such analyses can then motivate experimental efforts to test whether the identified candidate loci do in fact contribute to functional variation in some fitness‐related phenotype. Functional studies can provide corroborative evidence for positive selection at particular loci, and can potentially reveal specific molecular mechanisms of adaptation.     

Genomic Signatures of Recent Adaptation in a Wild Bumblebee

Environmental changes threaten insect pollinators, creating risks for agriculture and ecosystem stability. Despite their importance, we know little about how wild insects respond to environmental pressures. To understand the genomic bases of adaptation in an ecologically important pollinator, we analyzed genomes of Bombus terrestris bumblebees collected across Great Britain. We reveal extensive genetic diversity within this population, and strong signatures of recent adaptation throughout the genome affecting key processes including neurobiology and wing development. We also discover unusual features of the genome, including a region containing 53 genes that lacks genetic diversity in many bee species, and a horizontal gene transfer from a Wolbachia bacteria. Overall, the genetic diversity we observe and how it is distributed throughout the genome and the population should support the resilience of this important pollinator species to ongoing and future selective pressures. Applying our approach to more species should help understand how they can differ in their adaptive potential, and to develop conservation strategies for those most at risk.     

Working of the genetic code

The genetic code is used differently by different kinds of species. Each type of genome has a particular coding strategy, that is, choices among degenerate bases are consistently similar for all genes therein. This uniformity in the selection between degenerate bases within each taxonomic group has been discovered by applying new methods to the study of coding variability. It is now possible to calculate relative distances between genomes, or genome types, based on use of the codon catalog by the mRNAs therein.     

Playing Dr Jekyll and Mr Hyde: combined mechanisms of phase variation in bacteria

Phase variation is the adaptive process by which bacteria undergo frequent and reversible phenotypic changes resulting from genetic alterations in specific loci of their genomes. This process is crucial for the survival of pathogens and commensals in hostile and ever-changing host environments. Despite important differences in the molecular mechanisms that mediate and regulate phase variation, related strategies have evolved to generate high levels of genetic diversity through complex and combinatorial reshuffling of genetic information. Recent studies, supported by the emergence of global genomic approaches, have revealed that bacterial pathogens often use a combination of different mechanisms to vary the expression of a variety of biological functions, providing new insights into bacterial adaptation and virulence mechanisms. Recent advances in the understanding of the molecular mechanisms of phase variation are reviewed, and differences in these mechanisms outlined.     

Towards systematic functional characterization of cancer genomes

Whole-genome approaches to identify genetic and epigenetic alterations in cancer genomes have begun to provide new insights into the range of molecular events that occurs in human tumours. Although in some cases this knowledge immediately illuminates a path towards diagnostic or therapeutic implementation, the bewildering lists of mutations in each tumour make it clear that systematic functional approaches are also necessary to obtain a comprehensive molecular understanding of cancer. Here we review the current range of methods, assays and approaches for genome-scale interrogation of gene function in cancer. We also discuss the integration of functional-genomics approaches with the outputs from cancer genome sequencing efforts.