Limits on the Rate of Evolution Sally Otto Department of Zoology University of British Columbia

Rates of morphological evolution vary enormously...

Some species have changed rapidly in appearance over tens to hundreds of thousands of years. Cichlids in African rift lakes Columbines Sticklebacks in BC freshwater lakes Hawaiian Drosophila

Others have remained similar in appearance over tens to hundreds of million years. Crocodiles Sequoias Lungfish Monotremes

The largest unsolved puzzle in evolution What factors set the pace of evolutionary change? ?? l Rate of Environmental Change l Appearance of Mutations l Efficiency of Selection l Architectural Constraints …but what are their relative roles??

Fast rates of morphological evolution occur in novel environments... e.g. Honeycreepers on the Hawaiian islands RATE OF ENVIRONMENTAL CHANGE

and E. coli in a novel glucose environment (Lenski and Travisano 1994) but the rate slows in a static environments.

Evolution can only go where mutations lead it. The rate of beneficial mutation can limit the rate of evolution, especially in novel environments and in small populations. (de Visser et al 1999) APPEARANCE OF MUTATIONS

EFFICIENCY OF SELECTION Natural selection does not cause instantaneous adaptation. The spread of beneficial alleles takes time...

...and new beneficial alleles are often lost by drift. Aa but this is only an average. In a population of constant size, each parent produces one offspring, on average. Individuals carrying a new beneficial allele may have more offspring, say 1+s, on average...

In 1927, Haldane proved the classic result that the probability of fixation (P) of a new beneficial mutation is approximately 2s in a population of LARGE and CONSTANT size, ignoring other loci.

Where does 2s come from? l Poisson distribution of offspring per parent l One offspring per parent on average l 1+s offspring per parent carrying a rare beneficial mutation Branching Process When s is small, P is approximately 2s.

l expansions l contractions l fluctuations Natural populations do not, however, remain constant in size, but experience In populations changing in size (N t ), what is the probability of fixation of a new allele?

Exponential growth l 1+r for wildtype parents l (1+r)(1+s) for parents carrying a beneficial allele If a population is growing or shrinking, the average number of offspring per parent is not one but  P  2 (s + r) (Otto and Whitlock 1997)

Fixation probability with exponential growth: Diploid population of initial size 100.

Logistic Growth Ô 2 (s+r) when N t << K Ô 2s when N t approaches K Population growth is generally limited, however, and decreases as population size approaches carrying capacity (K).

Population Size Growing Shrinking | | 10 | s=0.001 s=0.01 PtPt 2s s=0.001 s= | 1000 | | Time (Measured by Population Size) (r=0.01, K=1000) (r=0.01, K=10000) 0.6

l more likely to fix in growing populations l less likely to fix in shrinking populations Beneficial mutations are: Population dynamics are as important as selection in determining the fate of new mutations. l less likely to fix in growing populations l more likely to fix in shrinking populations Deleterious mutations are:

Evolutionary forces will reinforce, rather than counteract, externally caused changes in population size.

ARCHITECTURAL CONSTRAINTS l Pleiotropy l Gene number l Linkage relationships Genomic architecture:

“As a result of complex biochemical, developmental, and regulatory pathways, a single gene will almost always influence multiple traits, a phenomenon known as pleiotropy.” - Lynch and Walsh (1998) I - Pleiotropy One Gene One Trait X One Gene Several Traits

Teosinte Maize Length of internodes in the ear Number of fruitcases in a row on the ear Tendency of ear to shatter % of fruitcases with single vs. two kernels % lateral branches with male tassels Degree to which fruitcases are stacked Number of internodes in the lateral branches Average length of these internodes Number of branches in the 1 o lateral inflorescence Doebley et al (1995) examined the effects of two QTLs on: è The two QTLs significantly affected 9/9 & 8/9 traits! Teosinte-Maize divergence

Consider a trait subject to direct artificial or natural selection. An allele that causes a direct beneficial effect (s d ) on this trait may fail to become established due to deleterious pleiotropic effects (s p ). Scenario

1. Fewer alleles are favourable overall (s T = s d + s p must be positive). 2. Among these, the overall selective advantage is lessened. How does pleiotropy affect the rate of evolution?

Pleiotropic selection (s ) p 0 Probability Uniform Half-normal Exponential These quantities can be calculated for any given distribution of pleiotropic effects.

Pleiotropic selection (s ) p 0 Probability Uniform s > 0 T - s d s < 0 T 1. Fraction favourable 2. Overall selective advantage

In general, when pleiotropy is extensive and strong… Only a fraction of alleles that are beneficial to the trait will be favourable overall. Among these, pleiotropy on average halves the selective advantage.

Implications Pleiotropy will slow evolutionary change, especially when selection acts weakly on novel functions ( GxE). The exact traits that have been favoured by natural selection will be difficult to identify, because even costly phenotypic changes may have arisen pleiotropically.

II - Gene Number When genetic change is constrained by pleiotropy, the rate of evolution may be increased by gene or genome duplication.

Polyploidy among animals Key polyploid events early in the evolution of vertebrates, ray-finned fish, salmonids, catostomids...

Gene conservation Among ancient polyploids, a surprisingly high fraction of gene duplicates are preserved: ~ 8-13% retained in duplicate in yeast (Wolfe & Shields 1997) ~ 50% retained in duplicate in vertebrates (Nadeau & Sankoff 1997) ~ 50% retained in duplicate in Xenopus (Hughes & Hughes 1993) ~ 50% retained in duplicate in salmonids & catastomids (Bailey et al 1978) ~ 72% retained in duplicate in maize (Ahn & Tanksley 1993) “Gene duplication...allows each daughter gene to specialize for one of the functions of the ancestral gene.” (Hughes 1994)

Rate of adaptation

Implications Polyploidy events have occurred repeatedly among animals and plants. Polyploids are not evolutionary dead-ends and may have higher rates of evolution. Polyploidization may have played a key role in evolution, freeing genes from the constraints of pleiotropy and allowing the evolution of more complex patterns of gene expression.

“For, unless advantageous mutations occur so seldom that each has had time to become predominant before the next appears, they can only come to be simultaneously in the same gamete by means of recombination.” - R. A. Fisher (1930) III - Genetic Associations

CONCLUSIONS Evolutionary change is limited by a variety of factors (environmental change, mutation, selection, genomic architecture). We are gaining a better appreciation for the effects of these various factors,but determining their relative roles remains one of the most important open questions in evolutionary biology.

Fisher-Muller Hypothesis aB AB aB AB aB Ab ab Mutation to b AB Mutation to a aB With recombination Without recombination Time

2 s 1.6 s 1.2 s 0.8 s 0.4 s Freq(b) Fixation Probability of a Time r= r= r=0.001 r= s a = 0.01 s b = 0.01 On-going selection at one locus (B) reduces the fixation probability of a new beneficial allele at a linked locus (A). - N. Barton (1995)

Evolution of recombination A modifier gene that increases recombination becomes associated with beneficial alleles that are more likely to fix. As these successful alleles spread, the modifier is dragged along by genetic hitchhiking.

By increasing the fixation probability of beneficial mutations, modifiers that increase recombination rise in frequency. - Otto & Barton (1997) Time Change in Modifier Freq(b) s a = 0.01 s b = 0.1 R = r MM = 0.01 r Mm = 0.02 r mm = 0.03

Selection acting on a modifier of recombination is  : 2 s  r / r for a tightly linked chromosome  2 s 3  r / N for a one Morgan chromosome : rate of beneficial mutations throughout population per chromosome per generation s:average selection coefficient of beneficial mutation r: average rate of recombination between genes  r:effect of modifier on r N: population size

The Fisher-Muller mechanism can select for increased recombination and sex within a population, but the effect is weak unless linkage is tight or beneficial mutations are common.