Sequencing the genome and beyond

Science is defined by continual progress and new technologies. This final chapter starts with introducing what it means to sequence and assemble a reference genome. It is easy to forget that the true genome is not linear but has structure and function. In this chapter the genome is explored as a 3D entity—from how it is transcribed, to how proteins interact with it, and finally to how it is actually structured. This also gives an opportunity to focus on epigenetics and how to interpret processes such as DNA methylation in an evolutionary context. The second part of the chapter focuses on ways we can interact with the genome—exploring how we might test the function and role that candidate genes play. The chapter introduces transgenics, in particular the transformative technology of CRISPR/CAS9, and explores how this might change the face of evolutionary biology in the near future.

The theory of natural selection

Natural selection is the scientific explanation for the evolution of adaptations. Wonders of the living world, such as the anatomy and physiology that grants the cheetah its unchallenged running speed; the seductive colors and scents of a flower that are irresistible to its pollinators; and the accuracy and sophistication of sense organs such as the human eye are the ultimate results of this one creative force in evolution. This chapter investigates simple models of natural selection to explore its power in causing evolutionary change. Mathematical techniques including invasion fitness analysis and adaptive landscapes are powerful tools for analyzing such models and for identifying evolutionarily stable and unstable equilibria. The chapter further investigates frequency-dependent selection and evolutionary game theory. An important goal here is to show that selection can take many different forms and yield very different evolutionary outcomes.

Reconstructing the past

How can genetics and genomics be used to understand the evolutionary history of organisms? This chapter focuses on such methods. First, the field of phylogenetics is introduced, as a way to visualize and quantify the evolutionary relationships among species. The chapter outlines how we go from aligning DNA sequence data to building gene trees and we argue that “tree-thinking” is fundamentally important for understanding evolution. The chapter also goes beyond phylogenetic trees to focus on phylogeography, i.e. the understanding of evolutionary relationships in a spatial context. More recently, the explosion of genomic data from ancient and modern human populations has made this an extremely exciting field which is transforming our understanding of our own evolutionary history. Before that, though, the chapter reviews how modern phylogenetics has arisen from historical efforts to classify life on Earth.

Inferring evolutionary processes from DNA sequence data

The allelic evolutionary genetic models explored so far are applicable to genetic markers. However, DNA sequences harbor a lot of information about the evolutionary past that would be missed if different sequences were simply treated as different alleles. This chapter introduces some important methods and concepts applicable to the analysis of DNA-sequence data. The null models for analyzing sequence data are derived from the neutral theory of molecular evolution. Historically, however, the neutral theory has made a large impact on evolutionary genetics. Therefore, this chapter starts by reviewing its important contribution. Then, important parameters and statistics for analyzing sequence variation are introduced, including a plethora of neutrality tests. The chapter ends with a cautious focus on the powerful tool of genome scan analysis and its utility for identifying regions of the genomes potentially under selection. This includes a section on more recently derived statistics which incorporate information on haplotype structure.

Changes in allele and genotype frequency

Evolution is the change in heritable traits of populations over successive generations. At the molecular level this translates into changes in their genetic composition. A general theoretical investigation of how different demographic and evolutionary processes affect genetic variation within and between populations provides us with tools to reconstruct evolutionary history. This is the fundamental purpose of population genetics. This chapter investigates the relationship between allele and genotype frequencies in a hypothetical population that is not subjected to any evolutionary forces—i.e. the Hardy–Weinberg model. Then, one by one, demographic and evolutionary factors such as non-random mating, genetic drift, selection, mutation, and gene flow are introduced to investigate in what ways they affect allele and/or genotype frequencies. The chapter further introduces F-statistics and goodness of fit tests to investigate statistical deviations from expectations.

Genetics and genomics of speciation

The diversity of life on Earth is something that has long fascinated biologists. When we inspect all this variation, two striking patterns emerge. First, organisms appear as if they have almost been “designed” to live the way they do. However, as explained in chapters 4 and 5, the theory of natural selection accounts for this apparent design. The second striking pattern is that variation appears to be non-randomly distributed. That is, it is clustered into groups of individuals that resemble each other and that are recognizably different from other such clusters; species, in other words. To what extent are species biologically meaningful entities in evolution? How do new species originate? What genetic changes occur when one species diverges into two? How is genomic data changing our understanding of speciation? These are among the many questions this chapter addresses. The chapter starts by discussing what constitutes a species.

Genomes and the origin of genetic variation

Error and chance events, random mutations, are necessary prerequisites for evolution to happen. In a perfect world with no mutations there would be no evolution because no genetic variation would be generated that natural selection or genetic drift could work upon. This chapter first reviews how DNA is organized into genomes and genes in bacteria, archaea, and, in greater detail, eukaryotes. A surprising finding is that only a small fraction of the eukaryote genome consists of coding sequence. Evolutionary processes that can explain the presence of large amounts of noncoding DNA and the repetitive structure of the genome are reviewed, with emphasis on the roles that selfish genetic elements and unequal crossing over play. The chapter further explores the mechanisms that cause mutation and how new genes and protein functions originate.

Multilocus evolution

Most phenotypic traits are affected by a multitude of genes, which may interact in complex ways. This means that the single locus model explored in chapters 3 and 4 is not always able to capture the full complexity of genetic evolution. In many cases, multiple genes are involved and so this chapter formalizes the analysis of multilocus evolution. Concepts such as linkage disequilibrium and epistasis are introduced, both of which are necessary to properly understand multilocus evolution. The currently highly active field emerging as a result of a crossover between quantitative genetics and genomics is further explored, including methods such as quantitative trait locus (QTL) analysis and genome wide association study (GWAS) that allow phenotypic variation to be associated with likely causative genes and that have made important advances in our understanding of the genetic underpinnings of disease.

The power of natural selection

Adaptations are the products of natural selection—traits that evolved because they proved useful at some level. Often adaptations evolved because they enhanced the survival or reproductive output of individuals, but selection can also operate at other levels—genes, individuals, populations, and species. Sometimes a genetic change has positive effects on all levels. A mutation that increases the survival of its carrier would increase in frequency; populations that become fixed for that allele may be less prone to extinction, which in turn may increase the longevity of that species. Other times there can be conflicting fitness effects at the different levels. This chapter explores the power of natural selection in shaping the living world by investigating the complexities of multilevel selection, biological solutions to heterogeneity and unpredictability in the environment, and how interactions between species can shape evolution. However, the chapter starts by investigating factors that may constrain adaptive evolution.

The foundations of evolutionary genetics

The fields of evolutionary biology and genetics were founded as separate disciplines in the mid-1800s, largely due to the works of Charles Darwin and Gregor Mendel respectively. It would, however, take decades before biologists finally understood the deep connection between the principles of heredity and the processes of evolution and that neither could be fully understood without the other. This chapter takes a brief look at the history of these disciplines, including how the key concepts, ideas, and technologies, fundamental to all of biology, were discovered and how these have affected our ways of thinking. Many important concepts are foreshadowed here that will be handled at greater depth in later chapters. The chapter ends with a brief review of important methods in contemporary evolutionary genetics and a hint towards future developments in the field.