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. 2005 Sep 2;272(1578):2277–2282. doi: 10.1098/rspb.2005.3217

Population size and molecular evolution on islands

Megan Woolfit 1,2,*, Lindell Bromham 2
PMCID: PMC1560185  PMID: 16191640

Abstract

The nearly neutral theory predicts that the rate and pattern of molecular evolution will be influenced by effective population size (Ne), because in small populations more slightly deleterious mutations are expected to drift to fixation. This important prediction has not been widely empirically tested, largely because of the difficulty of comparing rates of molecular evolution in sufficient numbers of independent lineages which differ only in Ne. Island endemic species provide an ideal test of the effect of Ne on molecular evolution because species restricted to islands frequently have smaller Ne than closely related mainland species, and island endemics have arisen from mainland lineages many times in a wide range of taxa. We collated a dataset of 70 phylogenetically independent comparisons between island and mainland taxa, including vertebrates, invertebrates and plants, from 19 different island groups. The rate of molecular evolution in these lineages was estimated by maximum likelihood using two measures: overall substitution rate and the ratio of non-synonymous to synonymous substitution rates. We show that island lineages have significantly higher ratios of non-synonymous to synonymous substitution rates than mainland lineages, as predicted by the nearly neutral theory, although overall substitution rates do not differ significantly.

Keywords: comparative method, molecular evolution, substitution rates, effective population size, dN/dS, molecular clock

1. Introduction

The nearly neutral theory of molecular evolution (Ohta & Kimura 1971; Ohta 1992) has become one of the most important foundations of modern sequence analysis. Although generally considered to be theoretically sound, it is not universally accepted (e.g. Gillespie 1991, 1999), and there have been few general empirical tests of some predictions arising from the theory. One such prediction which is amenable to further testing is the influence of effective population size (Ne) on the rate and pattern of molecular evolution. A decrease in Ne should lead to an increase in the rate of fixation of nearly neutral mutations—that is, mutations with selection coefficients on the order of the inverse of the effective population size—as selection is less effective in small populations (Wright 1931; Kimura 1983). Thus, if a substantial proportion of mutations are nearly neutral, overall substitution rate should increase in species with small Ne compared to those with larger Ne, provided mutation rates are similar in both species (Ohta 1972a). The ratio of non-synonymous to synonymous substitution rates (ω) is also predicted to increase in these species (Ohta 1993), as many non-synonymous mutations are expected to be nearly neutral, while synonymous mutations are more likely to be neutral and thus fix at a rate unaffected by Ne.

There have been relatively few empirical studies that have directly tested these predictions, due partly to the difficulty of identifying comparisons between species which differ only in effective population size. For example, while comparisons of rates of evolution in primates and rodents support the predictions (Wu & Li 1985; Weinreich 2001), these lineages differ in many other aspects of their biology which could affect substitution rates, such as generation time, metabolic rate and DNA repair mechanisms (Bromham et al. 1996). Similarly, endosymbiotic species of bacteria and fungi with small effective population sizes have significantly higher substitution rates and ω values than their free-living relatives (Moran 1996; Woolfit & Bromham 2003), but other biological changes associated with adoption of a symbiotic lifestyle may contribute to this pattern (Johnson & Seger 2001).

Comparisons between island endemic species and closely related mainland lineages offer an ideal test of the effect of Ne on the rate and pattern of evolution (Ohta 1972b; Llopart & Aguade 1999; Johnson & Seger 2001). Endemics are likely to have undergone both a severe population bottleneck during the initial colonization of an island and subsequent long-term reduction in census population size due to range restriction. Together, these factors are expected to frequently lead to a reduction in Ne relative to mainland species (e.g. Frankham 1997; Eldridge et al. 1999). Island endemics have arisen independently many times, in species as diverse as raspberries, weevils, toads and finches, and on islands ranging from tiny sub-Antarctic islets such as Campbell Island to the large, tropical island of Madagascar. Island and mainland relatives often share similar morphology, life history and ecology (e.g. Johnson & Seger 2001), and where they do not, the differences between island and mainland species are not expected to be systematically biased across a wide range of taxa (for example, trends for both increase and decrease in body size have been shown for island species; Clegg & Owens 2002). Any consistent trend in the rate or pattern of molecular evolution between island and mainland lineages is, therefore, likely to be due to differences in effective population size rather than some other aspect of their biology.

A number of previous tests of the effect of Ne on rates of molecular evolution have utilized data from island endemic species. Comparisons of ω values in a small number of island and mainland Drosophila lineages have yielded inconsistent results, possibly due to variation in codon usage bias among species (e.g. Ohta 1993; Llopart & Aguade 1999). A recent analysis of sequence data from island and mainland species of ducks and doves included a larger number of species, and found a significant increase in non-synonymous substitution rates in the island lineages (Johnson & Seger 2001). However, the datasets used in each of these previous analyses were taxonomically restricted, limiting the generality of the conclusions.

In order to conduct a general test of the influence of Ne on the rates and patterns of molecular evolution, we have collated a dataset of 70 phylogenetically independent comparisons between island and mainland species, with sequence data (including mitochondrial and nuclear, protein-coding and rRNA genes) from over 600 vertebrate, invertebrate and plant species, from 19 different island groups.

2. Material and Methods

(a) Data

We identified published datasets of DNA sequence data from closely related island and mainland species. To ensure that all species identified as ‘island’ species were true endemics, we confirmed the known ranges of all island species using a combination of recent literature, handbooks (e.g. del Hoyo et al. 1992) and online databases (e.g. http://www.natureserve.org).

Sequences for each dataset (consisting of island, mainland and outgroup species) were obtained from Genbank (http://www.ncbi.nlm.nih.gov/Genbank), and aligned by eye using Se-Al (Rambaut 1996). Where more than one gene was available for a dataset, the genes were concatenated and analysed together, as change in Ne resulting from demographic effects is predicted to affect genome-wide rates of substitution. Maximum likelihood (ML) phylogenetic trees were constructed using PAUP* (Swofford 2003), with an HKY+Γ model of nucleotide substitution (Hasegawa et al. 1985; Yang 1994).

Phylogenetically independent comparisons between island and mainland species were chosen from the ML trees (see Electronic Appendix table S1 for species included in each comparison). To be statistically independent, the paths connecting these comparisons on the tree must neither meet nor cross, to ensure that no data are used more than once in the analysis (Harvey & Pagel 1991). We used established taxonomy and previously published phylogenies based on morphological or DNA hybridization data, where available, to ensure that the comparisons chosen were consistent with accepted phylogenetic relationships.

(b) Analysis of ω

For each of the 44 comparisons containing protein-coding sequence data (see table 1), we used the CODEML program from PAML 3.13 (Yang 1997) to test whether island species had a higher ratio of non-synonymous to synonymous substitution rates (ω) than their mainland relatives. Branches on the tree were designated as belonging to island, mainland or outgroup classes (figure 1), and the value of ω was then estimated for each of these branch classes. These analyses were performed on unrooted trees (Yang 1997), but outgroup species were included in this analysis to increase the amount of data available for parameter estimation. The comparison was scored as positive if ω was higher for island branches than mainland branches, negative if it was lower. Each comparison contributed one point to a one-tailed Wilcoxon signed-ranks test across all comparisons. This test takes into account the magnitude of the difference in ω between island and mainland lineages as well as the sign of each comparison (Sokal & Rohlf 1995).

Table 1.

Relative substitution rates (island/mainland) and ratios of non-synonymous to synonymous substitution rates for island (IS ω) and mainland (ML ω) lineages for 70 independent comparisons (see Electronic Appendix for full list of species names).

taxon island(s) gene(s) relative substitution rate IS ω ML ω
vertebrates
 Acrocephalus 1 Macaronesia cytb 1.4715 0.0816 0.2062
 Acrocephalus 2 Madagascar, Seychelles cytb 0.8076 0.0277 0.0123
 Anairetes Juan Fernandez cytb, ND2 1.0513 0.0643 0.04
 Anas 1 Subantarctic cytb, ND2 8.4771 0.0819 0.0378
 Anas 2 Madagascar cytb, ND2 0.9232 0.0215 0.0236
 Anas 3 Phillipines cytb, ND2 2.8793 0.0281 < 0.0001
 Anas 4 Hawaii, Madagascar cytb, ND2 1.7029 0.0691 < 0.0001
 Anolis West Indies cytb 0.5631 0.0704 0.1183
 Bufo West Indies cytb, 12S, 16S 1.8487 0.0033 0.0029
 Chalcides Macaronesia cytb, 12S, 16S 2.1278 0.0107 0.0279
 Drepanidinae Hawaii cytb 1.1726 0.0019 < 0.0001
 Falco Madagascar, Mauritius, Seychelles cytb 0.9896 0.0261 0.0647
 Geospizinae Galapagos cytb 0.5986 0.0605 0.0245
 Lacerta Macaronesia cytb, COI, 12S 0.7057 0.039 0.0196
 Lemuridae Madagascar cytb, IRBP 0.7775 0.0977 0.0856
 Mabuya 1 Socotra cytb, COI, 12S 1.5738 0.0119 0.0092
 Mabuya 2 Macaronesia cytb, COI, 12S 32.0482 0.0196 0.0124
 Myadestes 1 West Indies cytb 0.7764 < 0.0001 0.0142
 Myadestes 2 West Indies cytb 1.0709 0.0106 0.0024
 Nesomyinae Madagascar cytb 0.9537 0.0138 0.016
 Regulus Macaronesia 16S 2.1198 — —
 Sylviidae Madagascar cytb 0.8656 0.0207 0.0212
 Tarentola 1 Macaronesia cytb, 12S 1.3683 0.0468 0.03
 Tarentola 2 Macaronesia cytb, 12S 0.4980 0.04 0.0573
 Tarentola 3 Macaronesia cytb, 12S 0.5222 0.0526 0.0744
 Tenrecidae Madagascar vWF, 12S, 16S 0.6540 0.2085 0.0619
 Vangidae Madagascar 12S, 16S 4.9250 — —
 Xantusiidae 1 California Channel cytb, 12S 0.7275 0.0517 0.0545
 Xantusiidae 2 West Indies cytb, 12S 0.8533 0.0532 0.0458
 Zenaida 1 Socorro cytb, ND2 1.9165 0.1569 0.0362
 Zenaida 2 Galapagos cytb, ND2 2.4174 0.0587 0.012
invertebrates
 Brachyderes Macaronesia COII 9.9626 < 0.0001 0.0061
 Celatoblatta Chatham COI 0.7309 0.0047 0.0019
 Drosophila Hawaii YP1 2.1216 0.3037 0.1108
 Dysdera Macaronesia COI 1.5143 0.0119 0.0175
 Galapaganus Galapagos COI 0.3768 0.0325 0.0688
 Geodorcus Chatham COI 0.2095 0.0044 0.0023
 Gonepteryx Macaronesia COI 2.0660 0.1467 0.0306
 Mandarina Bonin 16S 0.6424 — —
 Megalagrion Hawaii COII, EF1α 0.2580 0.036 0.0327
 Meladema Macaronesia COI 1.8450 0.0143 0.01
 Orsonwelles Hawaii COI, 16S 0.7334 0.0128 0.0112
 Pimelia Macaronesia COI 2.8382 0.0041 0.0108
 Steganacarus Macaronesia COI 3.7297 0.0096 0.0128
 Talitropsis Chatham COI 2.2770 0.0044 0.0023
 Tarphius Macaronesia COI 13.9775 0.0165 0.0133
 Thomisidae Hawaii COI 0.4193 0.003 0.0055
plants
 Asteriscus Macaronesia ITS, ETS 1.3181 — —
 Bencomia alliance Macaronesia ITS 5.8705 — —
 Bidens 1 Hawaii ITS 0.1354 — —
 Bidens 2 Starbuck ITS 0.9856 — —
 Coreocarpus California Baja ITS 1.0359 — —
 Erigeron Juan Fernandez ITS 0.2384 — —
 Genista Macaronesia ITS 0.2330 — —
 Geranium Hawaii rbcL 1.2503 — —
 Hesperomannia Hawaii ndhF 1.0294 — —
 Inuleae 1 Macaronesia ITS 0.5137 — —
 Inuleae 2 Macaronesia ITS 1.0224 — —
 Lavatera 1 Macaronesia ITS 0.4470 — —
 Lavatera 2 Macaronesia ITS 0.5278 — —
 Madieae Hawaii ITS 1.5509 — —
 Pericallis Macaronesia ITS 0.3512 — —
 Phylica Mauritius, St Helena, Tristan da Cunha ndhF 0.9212 — —
 Robinsonia Juan Fernandez ITS 0.5760 — —
 Rubus 1 Hawaii ndhF 4.1627 — —
 Rubus 2 Hawaii ndhF 1.6679 — —
 Sideritis Macaronesia ITS 2.2418 — —
 Sonchus Macaronesia ITS 2.8499 — —
 Teline Macaronesia ITS 4.9128 — —
 Viola Hawaii ITS 4.0606 — —
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Some taxa provide more than one independent comparison (e.g. Acrocephalus 1 and 2), each of which represents a separate colonization of an island from the mainland. Genes used in the analyses include mitochondrial genes (cytochrome b (cytb), NADH dehydrogenase subunit 2 (ND2), cytochrome oxidase subunit I (COI), cytochrome oxidase subunit II (COII), 12S small subunit ribosomal RNA (12S), 16S small subunit ribosomal RNA (16S)), nuclear genes (interphotoreceptor-binding protein (IRBP), von Willebrand factor (vWF), yolk protein 1 (YP1), elongation factor 1α (EF1α), internal transcribed spacer region (ITS), external transcribed spacer region (ETS)) and chloroplast genes (NADH dehydrogenase subunit F (ndhF) and ribulose 1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL)).

Figure 1.

Figure 1

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For the CODEML analysis, branches were assigned to one of three classes—island, mainland or outgroup (different rate classes are indicated using different shades of grey). The non-synonymous to synonymous substitution rate ratio (ω) was then estimated for each class. For the BASEML analysis, a single rate was estimated for mainland and outgroup lineages, and a second rate for island lineages.

(c) Analysis of overall substitution rate

For each of the 70 comparisons we compared the rate of substitution in island and mainland lineages using the BASEML program from PAML. The local clock model we implemented allowed branches in the rooted tree to take one of two substitution rates (Yoder & Yang 2000). A ‘basal’ substitution rate was estimated for all branches in the outgroup and mainland lineages, and a second substitution rate was then estimated for the branches in the island lineage relative to the basal rate. The comparison was scored as positive if the relative rate of the island branches was greater than one (i.e. faster than the mainland), or negative if it was less than one. Each comparison contributed one point to a one-tailed Wilcoxon signed-ranks test.

3. Results

Island lineages had significantly higher ω values than mainland lineages (27 positive: 17 negative comparisons; Ts=338; p=0.03; median island ω/mainland ω=1.20; table 1). This result is based on data from vertebrates and invertebrates only. Protein-coding sequence data was available for five plant datasets, but each of these trees contained branches with non-synonymous but no synonymous substitutions, and we could not include the resulting undefined values of ω in the analysis.

The trend towards increased ω in island lineages was consistently observed across both vertebrates and invertebrates, nuclear and mitochondrial genes and radiating and non-radiating lineages (Bromham & Woolfit 2004), although the trend was non-significant for most subsets of the data (see Electronic Appendix table S2 for statistics). There were no obvious differences in results for lineages from different islands, although too few comparisons were available from each island to test this formally. We found no significant association between island size and ω (Spearman's correlation rs=0.08, p=0.37).

When overall substitution rate was examined for all 70 comparisons, no significant difference was observed between island and mainland lineages (38 positive: 32 negative; Ts=1088; p=0.18; median island rate relative to mainland rate=1.04; table 1). We also performed a signed-ranks test on the substitution rate estimates using only those 44 comparisons with protein-coding sequence data that were included in the analysis of ω. Again, there was no significant pattern of rate increase in island species (p=0.29). Results were not qualitatively different when we reanalysed the data by comparing island rate relative to the outgroup with mainland rate relative to the outgroup.

4. Discussion

We have shown that island species tend to have significantly higher ratios of non-synonymous to synonymous substitution rates than their mainland relatives. This difference is best explained by an increase in nearly neutral mutations drifting to fixation in small island populations. The pattern of increase in ω we detected was consistent across genes, taxa and island groups. There is no a priori reason to believe that these diverse island endemic lineages differ systematically from their mainland relatives in generation time, body size, or other life history trait thought to affect molecular evolution. It is likely, however, that most island lineages experience a reduction in Ne. Reduced levels of heterozygosity and other population genetic markers of decreased Ne have been found in a broad range of island endemic vertebrates, invertebrates and plants relative to mainland species (Ellstrand & Elam 1993; Frankham 1997). Direct estimates of Ne were not available for a great majority of the datasets included in this analysis. However, even if a number of our datasets did include island taxa with Ne greater than or equal to that of their mainland relatives, this would not bias our results. These lineages should experience a reduction or no change in ω, and so would simply decrease the significance of the trend we see towards increased ω in island endemics across datasets.

This increase in ω is unlikely to be due to the adaptation of island endemic species to novel environments. The vast majority of the genes included in our analysis are housekeeping genes, which are more likely to be evolving under purifying selection, to maintain their essential functions, than positive selection (Zhang & Li 2004). Furthermore, the diversity of the data in our analysis makes it unlikely that our results could be due to positive selection: we have included data from genes coding for components of different metabolic pathways, from many species filling a vast range of ecological niches.

Island endemics may alternatively experience relaxed selective constraints, allowing the fixation of more slightly deleterious mutations, and thus increasing ω. Many niches may be vacant during the early stages of colonization of an island, reducing competition for resources. Colonizing populations tend to carry only a fraction of the parasites hosted by the originating population (Mitchell & Power 2003; Torchin et al. 2003), and island endemics may also encounter fewer herbivores or predators, leading to relaxed selection on many kinds of defence mechanisms (e.g. Bowen & Van Vuren 1997). Other island endemic species, however, experience strong competition for limited resources, harsh environmental conditions and heavy mortality (e.g. Wright 1999). Any relaxation of purifying selection which does occur is, in any case, unlikely to act across a broad range of genes and taxa, as would be required to explain the pattern of increased ω that we observe.

Although an increase in substitution rate has previously been demonstrated for a number of lineages with reduced Ne (e.g. Kliman et al. 2000; Woolfit & Bromham 2003), we did not detect any significant change in overall substitution rate in island endemic lineages. It is possible that, in these datasets, the signal of a consistent small change in the rate of fixation of nearly neutral mutations is being overwhelmed by the ‘noise’ of random variation in mutation rate between island and mainland lineages. Such variation in mutation rate is not expected to affect the analysis of ω. Selection on synonymous sites (Akashi 1999; Comeron et al. 1999) may reduce the sensitivity of the analysis of ω, but would not bias our results: such selection would reduce the likelihood of detecting a significant increase in ω in island species, and our test is therefore a conservative one. It seems likely that the increase in ω values in island lineages is a robust result, and the absence of significant change in overall substitution rate, while not supporting the nearly neutral theory, is not in conflict with it.

5. Conclusions

We have shown, for a diverse group of vertebrate and invertebrate lineages, that island endemic species have significantly higher non-synonymous to synonymous substitution rate ratios than their mainland relatives. This increase in ω is most likely caused by increased fixation of nearly neutral mutations due to reduction in effective population sizes in island endemic lineages. Our results support a key assertion of the nearly neutral theory, that the fixation of neutral and nearly neutral mutations by drift is a significant force in molecular evolution.

Acknowledgements

We wish to thank Adam Eyre-Walker, David Harper, Andrew Rambaut, Jon Seger and John Welch for useful discussions, and Marcel Cardillo and Ted Phelps for statistical assistance.

Supplementary Material

rspb20053217s02.pdf (179.9KB, pdf)

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rspb20053217s02.pdf (179.9KB, pdf)

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