Fundamentals of Molecular Evolution*

This chapter discusses some fundamental concepts of molecular evolution—that is, the evolution of genome and genetic diversity. The chapter discusses why an understanding of molecular evolutionary principles is important to understand the rationale for bioinformatic analyses. Basic premises of Darwinism are discussed along with a description of the pioneering work demonstrating “Darwinism in the test tube.” The molecular basis of heritable genetic variations and factors affecting gene frequency in a population are highlighted. The discussion moves on to the neutral theory of molecular evolution and molecular clock hypothesis. A simple method for determining signatures of positive (Darwinian) selection is also described. The relationship between biological classification and molecular phylogenetics is emphasized, along with a brief description of phenetics, cladistics, and evolutionary classification. The chapter concludes with a very brief introduction to the concept of the phylogenetic tree, which is discussed in more detail in Chapter 9.

Keywords

natural selection; genome evolution; Hardy–Weinberg equilibrium; neofunctionalization; subfunctionalization; population bottleneck; founder effect; neutral theory; molecular clock; selective sweep; hitchhiking effect; cladistics

Outline

2.1 Bioinformatics, Molecular Evolution, and Phylogenetics

Probably, the shortest classical definition of evolution is descent with modification from the ancestor. Evolutionary changes lead to changes in the inherited characters in a populationa. The ultimate outcome of evolution is the formation of new species (speciation), but evolution can generate diversity at all possible levels of biological organization including at the level of macromolecules, such as DNA and proteins.

Molecular evolution is a relatively recent discipline that has developed since DNA and protein sequence information became available. Simply stated, molecular evolution is evolution at the level of nucleic acids and proteins. At the molecular level, the primary cause of evolution is the accumulation of changes in genomic sequence (hence proteins as wellb). Therefore, evolution results in alteration of the genetic composition (gene pool) of a population over time. Changes in gene pool are associated with changes in gene frequency in a populationc.

The work of Emile Zuckerkandl and Linus Pauling between 1960 and 1965, particularly their seminal publication in 1965,1 is credited with ushering in a change in evolutionary thinking from the level of species to the level of macromolecular sequence. Such a paradigm shift in evolutionary thinking from population to macromolecular sequence essentially paved the way for the birth of a new field, molecular evolution. The classical definition of evolution as descent with modification refers to the event of speciation—that is, the formation of new species from an ancestral species. The same definition and concepts also apply to molecular evolution except for the fact that the targets of molecular evolution are nucleic acid and protein sequences. The causes of molecular evolution, such as mutation, recombination, gene conversion, duplication and divergence of genes, de novo origin of new genes, and structural and functional evolution of genomes, as well as changes in gene frequency in a population, are also at the heart of evolution at the level of species and beyond.

The availability of the complete genome sequence of many species provides a wealth of data and information for molecular evolutionary studies and comparative genomics. Evolutionary biology provides the scientific context and bioinformatic analysis utilizes the analytical tools for comparative genomics. In the context of evolutionary biology, the goal of various applications of bioinformatics, such as sequence alignment, sequence identity/similarity search, motif analysis, sequence homology analysis, chromosomal synteny analysis, and making phylogenetic trees, is to trace the signature and determine the rate of molecular evolution, as well as study the relatedness of taxa. Following the spirit of the now-famous statement by Dobzhansky that “nothing in biology makes sense except in the light of evolution, ”Higgs and Attwood (2005) have stated, “nothing in bioinformatics makes sense except in the light of evolution”.2 This is a very astute way of summarizing the relationship between bioinformatics and molecular evolution.

It has become a standard practice in studies involving DNA or protein sequence to obtain a phylogenetic tree and assess sequence divergence. Freely available software on the web has made it almost effortless to input the data and quickly get an output. Because of such widespread use of DNA and protein sequence analysis and phylogenetic inference, it is important to understand the principles of molecular evolution. The following narrative summarizes some fundamental concepts of molecular evolution that help in understanding the evolutionary foundations of bioinformatics.

2.2 Biological Evolution and Basic Premises of Darwinism

Biological evolution is most simply defined as descent with modification; the modification may be small scale (e.g. changes in gene/protein sequence) or large scale (e.g. speciation). After life had originated on Earth about 3.6 billion (3600 million) years ago, it evolved from simple to progressively complex forms, all from one primordial ancestral form, called the last universal common ancestor (LUCA). The evolutionary history of the descendants of LUCA constitutes the tree of life.

Evolution of life is a continuous process involving splitting of lineages, divergence of the descendants, and adaptive radiation into different environments (ecological niches) creating phenotypic diversity, and ultimately leading to reproductive isolation and the formation of new species (speciation). It is important to note in this context that even though “species” is an accepted taxonomic category, the concept of species and speciation is a hotly debated issue even 150 years after the publication of Darwin’s On the Origin of Species. We will follow the most widely used definition of species, provided by the biological species concept.

Two pioneering architects of the biological species concept were Theodosius Dobzhansky and Ernst Mayr. According to Mayr’s classical definition of species, “species are groups of actually or potentially interbreeding natural populations that are reproductively isolated from other such groups”d.3 In other words, a species is a reproductive community that represents a unique gene pool. Genetic exchange between members of two different gene pools is usually not successful in producing fertile offspring that could perpetuate the existence of the species. When populations within a species become isolated by geography, mate selection, or other means that interfere with mating, they may start to diverge and over time may evolve into new species.

Darwin’s theory of...