From molecular genetics to phylodynamics: evolutionary relevance of mutation rates across viruses

Abstract

Although evolution is a multifactorial process, theory posits that the speed of molecular evolution should be directly determined by the rate at which spontaneous mutations appear. To what extent these two biochemical and population-scale processes are related in nature, however, is largely unknown. Viruses are an ideal system for addressing this question because their evolution is fast enough to be observed in real time, and experimentally-determined mutation rates are abundant. This article provides statistically supported evidence that the mutation rate determines molecular evolution across all types of viruses. Properties of the viral genome such as its size and chemical composition are identified as major determinants of these rates. Furthermore, a quantitative analysis reveals that, as expected, evolution rates increase linearly with mutation rates for slowly mutating viruses. However, this relationship plateaus for fast mutating viruses. A model is proposed in which deleterious mutations impose an evolutionary speed limit and set an extinction threshold in nature. The model is consistent with data from replication kinetics, selection strength and chemical mutagenesis studies.

Figure 1. Mutation and evolution rate estimates for the major groups defined by the Baltimore classification of viruses.

a: mutation rates; b: evolution rates. Each data point corresponds to an individual estimate. Bars indicate log-scale (geometric) means.

Figure 2. Relationship between mutation and evolution rates across viruses.

Symbols for each Baltimore group are the same as in Figure 1. a: evolution rates versus mutation rates for seven viruses (HSV-1: herpes simplex virus 1; TMV: tobacco mosaic virus; AHBV: avian hepatitis B virus; FLUVA: influenza A virus; HIV-1: human immunodeficiency virus 1; PV-1: poliovirus 1; HCV: hepatitis C virus). b: log-scale mean ± SEM mutation and evolution rates for each Baltimore group. The dotted line indicates the prediction from a purely neutral model, whereas the dashed line corresponds to a model that incorporates deleterious mutations.

Figure 3. Expected relationship between mutation and evolution rates according to the neutral-deleterious evolution model for four human viruses: HCV (hepatitis C virus), PV-1 (poliovirus 1), FLUVA (influenza A virus), and HIV-1 (human immunodeficiency virus 1).

Curves indicate the prediction obtained using log₁₀ a = 2.387, b = 3.744, and the corresponding genome size of each virus. White dots show the observed average rates. These four viruses were chosen for representation because of the relatively high number of estimates available (see and Text S1). Fewer data are available for the other three viruses appearing in Figure 2a, and their predicted rates deviated more from the observed values.

Figure 4. Viral evolution rate versus genome size.

a: DNA viruses; b: RNA viruses. The least-squares linear regression lines are shown. Symbols for each Baltimore group are the same as in Figure 1.