Molecular evolution

8.1 The neutral theory

• The neutral theory and its predictions for levels of polymorphism and rates of divergence.

• The nearly neutral theory.

The field of molecular evolution involves the study of DNA, RNA, and protein sequences with the goal of elucidating the processes that cause both change and constancy among sequences over time. One approach to molecular evolution is to focus on a specific gene, seeking to test hypotheses about what parts of that specific sequence are most likely involved in some function or in the regulation of transcription. Another type of inquiry in molecular evolution involves testing hypotheses about the population genetic processes that have operated on sequences in the past using DNA sequence data. This latter type of research often seeks to distinguish whether a pattern of variation in a sample of DNA sequences is consistent with genetic drift or with certain forms of natural selection. The common feature of all hypothesis tests in studies of molecular evolution is the use of null and alternative hypotheses for the patterns and rates of sequence change. This chapter will introduce the conceptual foundations behind many of the most commonly used null and alternative hypotheses in molecular evolution. Although this chapter focuses exclusively on DNA sequences, the concepts presented are sometimes applicable to protein sequences as well.

The neutral theory now forms the basis of the most widely employed null model in molecular evolution. The neutral theory adopts the perspective that most mutations have little or no fitness advantage or disadvantage and are therefore selectively neutral. Genetic drift is therefore the primary evolutionary process that dictates the fate (fixation or loss) of newly occurring mutations. When it was originally proposed, the neutral theory was a major departure from orthodox population genetic theory of the time.

In the 1950s and 1960s, it was widely thought that most mutations would have substantial fitness differences and therefore the fate of most mutations was dictated by natural selection. Motoo Kimura (shown in Fig. 8.1) argued instead that the interplay of mutation and genetic drift could explain many of the patterns of genetic variation and the evolution of protein and DNA sequences seen in biological populations (Kimura 1968, reviewed in Kimura 1983a). King and Jukes (1969) also proposed a similar idea at around the same time. (The controversy generated by the neutral theory as well as some of the logic behind Kimura's proposal of the neutral theory is

Figure 8.1 Motoo Kimura (on left) and James Crow in 1986 on the occasion of Kimura being awarded an honorary doctoral degree at the University of Wisconsin, Madison, WI, USA. Kimura pioneered the use of diffusion equations to determine quantities such as the average time until fixation or until loss for neutral mutations. Based on these foundations, he proposed the neutral theory of molecular evolution in 1968. Kimura and Crow collaborated to develop some of the basic expectations for neutral genetic variation. Crow mentored and encouraged many people who became influential contributors to population genetics, including Kimura. Photograph kindly provided by J. Crow.

Figure 8.1 Motoo Kimura (on left) and James Crow in 1986 on the occasion of Kimura being awarded an honorary doctoral degree at the University of Wisconsin, Madison, WI, USA. Kimura pioneered the use of diffusion equations to determine quantities such as the average time until fixation or until loss for neutral mutations. Based on these foundations, he proposed the neutral theory of molecular evolution in 1968. Kimura and Crow collaborated to develop some of the basic expectations for neutral genetic variation. Crow mentored and encouraged many people who became influential contributors to population genetics, including Kimura. Photograph kindly provided by J. Crow.

covered in Chapter 11.) The neutral theory null model makes two major predictions under the assumption that genetic drift alone determines the fate of new mutations. One prediction is the amount of polymorphism for sequences sampled within a population of one species. The other prediction is the degree and rate of divergence among sequences sampled from separate species.

Polymorphism

The balance of genetic drift and mutation that determines polymorphism in the neutral theory is diagrammed in Fig. 8.2. Each line indicates the change in frequency of an allele over time. New mutations enter the population (lines at the bottom edge) and their frequency in the population then changes due to genetic drift. The frequency of each allele is therefore a random walk between fixation and loss. To see how this random walk results in polymorphism, hold a straight edge such as a ruler to form a vertical line at any single time point. If the vertical line intersects any allele frequency lines, then the population has genetic polymorphism at that time point since there are multiple alleles segregating in the population. More alleles segregating in the population indicate more polymorphism. Segregating alleles, and therefore polymorphism, result from the random walk in frequency that each mutation takes under genetic drift. Most mutations segregate for short periods of time and then are lost from the population. However, since their frequency is dictated by random sampling, some alleles may reach high frequencies before eventually being lost. A small proportion of mutations will eventually be fixed in the population after a random walk in allele frequency. Under neutral theory, polymorphism results from the transient dynamics of allele frequencies before they reach fixation or loss end points. The process that underlies Fig. 8.2 can be approximately simulated in Interact box 5.1.

The neutral theory's prediction for levels of polymorphism in a population follows directly from the predicted dynamics of allele frequency under genetic drift (see Chapters 3 and 5). Chapter 3 showed that the initial frequency of an allele is also its chance

Divergence Fixed genetic differences that accumulate between two completely isolated lineages that were originally identical when they diverged from a common ancestor. Polymorphism The existence in a population of two or more alleles at one locus. Populations with genetic polymorphisms have heterozygosity, gene diversity, or nucleotide diversity measures that are greater than zero.

0 0

Post a comment