4/3/13
Does life history affect molecular evolutionary rates?
By: Gerardo Antonio Cordero (Department of Ecology, Evolution and Organismal Biology, Iowa
State University) & Fredric Janzen (Department of Ecology, Evolution and Organismal Biology,
Iowa State University) © 2013 Nature Education
Citation: Cordero, G. A. & Janzen, F. (2013) Does life history affect molecular
evolutionary rates? Nature Education Knowledge 4(4):1
The molecular evolutionary rate measures the frequency with which DNA or protein sequence
mutations are fixed (i.e., shared by most individuals) in a population. On the other hand, the
mutation rate refers to the amount of change in a DNA or protein sequence for a given unit of
time. These two intrinsically related processes have been key to our basic understanding of
molecular evolution. For example, the molecular clock theory (Zuckerkandl & Pauling 1962)
predicts an increase in fixed amino acid mutations of protein sequences as a function of time.
The molecular evolutionary rate is then expected to be constant, assuming that mutation rates
are the same across the evolutionary lineages of a given protein (Figure 1). The neutral theory of
molecular evolution (Kimura 1983) explains this pattern by proposing that most mutations do
not have an effect on the fitness of an organism. Under this model, fixed DNA nucleotide
mutations that do not result in changes to protein sequences are referred to as neutral or
synonymous substitutions. Also, beneficial mutations are expected to be rare and deleterious
ones quickly removed by natural selection. Although the molecular clock and neutral theories
are foundational to modern molecular biology, they do not always explain why evolutionary
rates vary among genes, proteins, and species. As a result, biologists have begun to consider
how organismal-level traits such as life history could influence variation in molecular evolution
across the tree of life. This is a central pursuit in evolutionary biology as it is relevant to key
concepts such as speciation and the ability of an organism to adapt.
1/7
4/3/13
Figure 1: Under a molecular clock, fixed amino acid mutations of a protein sequence (vertical axis) increase
as a function of time (hotizonal axis).
Thus, the molecular evolutionary rate is expected to be constant (bold line). Each dot represents divergent
evolutionary lineages of a given protein. Proteins in divergent evolutionary lineages that are not plotted on the line
represent deviations from theory. Those to the left of the line are expected to have accelerated rates of evolution,
while those to the right are expected to have decreased rates.
© 2013
Nature Education Modified from concepts in Graur & Li 2000. All rights reserved.
Molecular Evolution and Life history
What determines variation in the mutation rate and ultimately the molecular evolutionary rate?
The answer to this question is debatable for a number of reasons. Evidence at the cell and
molecular levels clearly supports the finding that mutations often derive from DNA replication
errors or mutagens in the environment. Organismal-level traits and population genetic
processes, in turn, could influence the frequency of DNA replication errors and mutagen levels.
Mutations are transmitted from generation to generation in the germ cell line of sexually
reproducing organisms. Because DNA in germ cells replicates during meiosis (gamete
differentiation), we expect short-lived species to have higher mutation rates. For example, mice
2/7
4/3/13
reproduce frequently and have short generation times. Their germ cell lines undergo more
rounds of meiosis, thereby increasing the chances of DNA replication errors. Compared to longlived species, mice also are expected to have larger populations with more individuals that are
available to reproduce — that is, a larger effective population size. Consequently, synonymous
(i.e., neutral) mutations are more likely to occur, leading to higher molecular evolutionary rates.
Furthermore, the larger effective population size promotes selection against non-synonymous
mutations that reduce fitness, thereby removing them from the population. Clearly, the
nucleotide chains that comprise the nuclear and organellar genomes of eukaryotic cells do not
evolve independently of organismal-level traits such as life history.
Broadly speaking, life history refers to traits that function to regulate the life cycles of species
(Roff 2002) (Figure 2). Examples of such traits include the timing of reproductive effort or its
magnitude (fecundity). When is the best time to reproduce for an organism in a given habitat?
How often does reproduction take place? These life-history traits are interrelated, making their
potential effects on molecular evolutionary rates difficult to discern. However, biologists have
proposed two models that establish a clear link between life history and molecular evolution:
the generation time and metabolic rate hypotheses. The generation time hypothesis, illustrated
in the mouse example, is related to the metabolic rate hypothesis because short-lived species
with smaller body size usually have higher metabolic rates. Specifically, the metabolic rate
hypothesis predicts that species with high metabolic rates have increased mutation rates due to
mutagenic elements resulting from mitochondrial respiration (Galtier et al. 2009). Sometimes
free oxygen radicals generated during respiration escape the mitochondrial electron transport
chain that produces energy for the cell. These molecules cause damage to nearby mitochondrial
DNA by oxidizing nucleotides.
Figure 2: Organisms employ reproductive strategies that are adapted to their habitats.
In this comparison, humans have a Type I survivorship curve in which a high percentage of offspring survive to
adulthood and generation time is long. Frogs feature an opposite pattern (Type III) in which high numbers of
offspring are produced but few survive. The small percentage that survives reaches adulthood quickly to produce
3/7
4/3/13
high offspring numbers. Birds display an intermediate strategy (Type II).
Photo courtesy of Ray Husthwaite.
To determine whether life-history traits such as generation time or metabolic rate affect
molecular evolutionary rates, it is necessary to make comparisons across multiple evolutionary
lineages. Molecular evolutionary rates and life-history differences among taxonomic groups are
contrasted after accounting for shared common ancestry. The rate of molecular evolution is
measured by using computer algorithms that estimate the number of substitutions (fixed
mutations) per unit time in DNA sequences. This process is aided by using adequately dated
fossils and well-supported hypotheses on the evolutionary relationship of species. We will
briefly explore recent case studies that have adopted such approaches. Some of the most
striking examples that illuminate the relationship between life history and molecular
evolutionary rates are from plant and animal genomes.
Life History and Molecular Evolution in Plants
Differences in life-history strategies within taxonomic groups of flowering plants appear to
influence molecular evolutionary rates (Figure 3). A comprehensive phylogenetic assessment of
angiosperms found that rates of DNA sequence (chloroplast + mitochondrial + nuclear)
evolution in long-lived (perennial) species are low compared to those of short-lived (annual)
species (Smith & Donoghue 2008). This finding was consistent with the generation time
hypothesis, and the results were subsequently validated by genome-wide assessments on
model plant species. However, correlations were stronger in nuclear genomes as these featured
higher molecular evolutionary rates than those of chloroplasts (Yue et al. 2010). Even when
taking into account that some annual plant species are self-breeding, generation time still
emerges as the strongest life-history correlate of molecular evolutionary rates (Muller & Albach
2010). Overall, the generation time hypothesis is the best-supported life-history model that
explains molecular evolutionary rate variation in plants. There is little evidence to support the
metabolic rate hypothesis in plants, although mitochondrial evolutionary rates are generally
lower compared to those of animals.
4/7
4/3/13
Figure 3: Difference in the molecular evolutionary rate of annual (herbs) vs. perennial (trees) plants.
© 2013
Nature Education (tree) Courtesy of Cordero. (flower) Photo via Wikimedia Commons. All rights
reserved.
Life History and Molecular Evolution in Animals
Among mammals, mitochondrial evolutionary rates range from one substitution per 1-2 million
years to one substitution per more than 100 million years — a difference of 2 orders of
magnitude (Nabholz et al. 2008A). Following the assumption that animal body size is correlated
with metabolism, theoretical models strongly support the idea that molecular evolutionary rate
variation is influenced by basal metabolic rate (Gillooly et al. 2005). In practice, support for this
hypothesis is limited because few studies have addressed mutations in the germ cell line
(Galtier et al. 2009). Germ cell line mutation rate was assessed in mutant strains of the
nematode Caenorhabditis elegans with deficiencies in the mitochondrial electron transport
chain. However, this experimental approach did not provide evidence for an increase in
mitochondrial DNA mutation due to metabolic oxidative stress (Joyner-Matos et al. 2011).
The relationship between life history and molecular evolutionary rates is more apparent in
animal nuclear genomes. While a study on the effect of 14 life-history traits on molecular
evolutionary rates of mitochondria in mammals did not provide strong support for the
generation time hypothesis (Nabholz et al. 2008B), life history appears to influence molecular
5/7
4/3/13
evolution in the nuclear DNA of mammals (Bazin et al. 2006). Evidence suggests that their
nuclear genomes evolve according to expectations from neutral theory. For example, the
nuclear DNA of humans has a lower molecular evolutionary rate compared to primates that have
shorter generation times. Specifically, in mammals, neutral evolutionary rates depend on
generation time, while non-synonymous rates depend on population size (Nikolaev et al. 2007).
Similar patterns have been demonstrated in invertebrate animals with the exception that
generation time was correlated with non-synonymous rates (Thomas et al. 2010). These studies
further support the generation time hypothesis, but we must keep in mind that it is not
mutually exclusive from population size effects.
Does life history drive molecular evolutionary rates?
We have discussed evidence to support the idea that molecular evolutionary rates are driven by
life history. By comparing differences among a wide variety of organisms, biologists can test the
prediction that DNA nucleotide sequences do indeed evolve according to a rate that, at least
partially, depends on organism-level traits. Generation time and metabolism, each to some
degree or in combination, affect the mutation rates of some organisms and, thus, their
molecular evolutionary rates. Even so, some relationships among generation time, metabolism,
and molecular evolution depend on whether the organism is a plant or an animal and the
location of the genome within the cell (i.e., nuclear vs. organellar). Also, differences in neutral
vs. non-synonymous rates, when averaged together across long DNA sequences, could further
complicate interpretations.
Our understanding of variation in molecular evolutionary rates is likely to improve when more
knowledge from molecular and organismal biology is made available. It is important to point
out that the drivers of variation in molecular evolutionary rate even among genomic regions of a
single species are not entirely understood. Work focusing on hypotheses concerned with DNA
repair mechanisms, environmental effects, gene duplication, hypermutable nuclear DNA
regions, population genetics, and sex-specific mutation bias may provide additional insights as
to why rates of molecular evolution vary within and among species. An appreciation of these
processes is necessary to clarify the origins of biological diversity and other evolutionary
phenomena.
References and Recommended Reading
Bazin, E.
et al. Population size does not influence mitochondrial genetic diversity in animals. Science 312, 570-572 (2006).
Galtier, N.
et al. Mitochondrial whims: Metabolic rate, longevity and the rate of molecular evolution. Biology Letters 5, 413-
416 (2009).
et al. The rate of DNA evolution: effects of body size and temperature on the molecular clock. Proceedings of
the National Academy of Sciences (USA) 102, 140-145 (2005).
Gillooly, J. F.
Graur, D., & Li, W.-H. Fundamentals of Molecular Evolution. Sunderland, MA: Sinauer Associates, 2000.
et al. No evidence of elevated germline mutation accumulation under oxidative stress in Caenorhabditis
elegans. Genetics 189, 1439-1447 (2011).
Joyner-Matos, J.
Kimura, M.
The Neutral Theory of Molecular Evolution. Cambridge, UK: Cambridge University Press, 1983.
6/7
4/3/13
Veronica L. (Plantaginaceae): Disentangling the influence of life history and
breeding system. Journal of Molecular Evolution 70, 40-56 (2010).
Muller, K., & Albach, D.C. Evolutionary rates in
et al. Strong variations of mitochondrial mutation rate across mammals-the longevity hypothesis. Molecular
Biology and Evolution 25, 120-130 (2008A).
Nabholz, B.
Nabholz, B.
et al. Determination of mitochondrial genetic diversity in mammals. Genetics 178, 351-361 (2008B).
et al. Life-history traits drive the evolutionary rates of mammalian coding and noncoding genomic elements.
Proceedings of the National Academy of Sciences (USA) 104, 20443-20448 (2007).
Nikolaev, S.I.
Roff, D.
Life History Evolution. Sunderland, MA: Sinauer Associates, 2002.
Smith, S. A., & Donoghue, M. J. Rates of molecular evolution are linked to life history in flowering plants.
Science 322, 86-89
(2008).
Thomas, J. A.
et al. A generation time effect on the rate of molecular evolution in invertebrates. Molecular Biology and
Evolution 27, 1173-1180 (2010).
Yue, J.-X.
et al. Genome-wide investigation reveals high evolutionary rates in annual model plants. BMC Plant Biology 10,
242 (2010).
Zuckerkandl, E. & Pauling, L. B. "Molecular disease, evolution, and genetic heterogeneity," in
Horizons in Biochemistry, eds. M. Kasha & B. Pullman.(New York: Academic Press, 1962)189225.
7/7