I recently published a paper that I wanted to introduce here – but I had been delaying because my posts usually start with some sort of silly introduction that I attempt to segue into something more scientific. I didn’t have the silly intro I needed until yesterday. Christmas brought it gift wrapped.
My daughter Aspen came home from her last day of school before Christmas quite pleased with herself for having won a class debate. The topic was: “For Christmas, which is better: a single large present or many small presents.” To hear Aspen tell it, the debate started off with about 80% of the students on the many-small side but, after she argued the single-large side, the proportions switched. “What were your arguments?” I asked her. Very seriously, she pointed out that “Big presents are more likely to be expensive and higher quality, and you will appreciate a big present more and spend more time with it and treasure it more.” Fair enough. I am convinced.
Evolutionary biology has also been having a many-small versus few-large debate. The key question has been – at its simplest – whether adaptation is driven by many genes of small effect or by few genes of large effect. The weight of opinion was classically toward many genes of small effect as represented by the field of quantitative genetics and made most stark by Fisher’s infinitesimal model. More recently, however, a perceptible shift has occurred toward the few-large side of the battle. The prime reason has been the recent publication in high-profile journals of various genes FOR this trait or FOR that trait – and, probably even more influentially, repetition as such in the popular press absent the caveats usually tendered in the original publications.
Variation in some traits is clearly influenced by only a few genes (Mendel’s peas being the icon) and the infinitesimal model is clearly unrealistic in its caricatured form (an infinite number of genes of miniscule effect). However, the vast weight of evidence remains – even in this new gene-centered world – squarely in the lap of many genes of small-to-modest effect. In the paper this post introduces, I provide three main reasons, reproduced here in shortened form (and without the examples and citations):
(1) Current genomic methods are strongly biased against genes of small effect. This bias is particularly obvious in candidate gene approaches, which deliberately target just the opposite. A strong bias is also present in linkage and association mapping, where estimation problems arise when relevant alleles are found at low frequency, when not enough recombination has occurred to break up large linkage blocks, when the number of individuals is few, when the number of loci is few, when the effect size of alleles is small, and from the need to assume a high threshold effect size to reduce study-wide type-I errors.
(2) Nearly all studies have sought to explain variance in specific traits, rather than overall adaptation (or ‘fitness’). This distinction is critical because overall adaptation to a given environment will be influenced by many traits. As a result, even the genes explaining high levels of variation in a particular trait might contribute little to overall fitness differences.
(3) Genome scans typically reveal that high-differentiation outliers, presumably influenced by divergent selection, represent 5–10% of the genome—and the distribution of these loci clearly implicates multiple unlinked genes.
The explosion of modern genetic technology has forced a re-evaluation of the many-small versus few-large debate, as well as many other cherished and entrenched ideas. Some classic ideas will stay with us, others will come to rest in the same place as my parent’s 8-track tapes, and perhaps others will end up somewhere in the middle (vinyl! – my brother is getting a record player for Christmas and I want one too).
While writing my book on Eco-Evolutionary Dynamics (nearly done!), I found myself mostly discussing phenotypes for which the genetic basis was unknown. I am not apologetic about this, of course, because phenotypes are the foundation of ecological effects on evolution (phenotypes are directly under selection, whereas genes are only indirectly under selection through their effects on phenotypes) and of evolutionary effects on ecology (phenotypes have direct effects on ecological processes, whereas genes have only indirect effects through their effects on phenotypes). However, lest readers say “Your book should be called Eco-Phenotypic Dynamics”, I figured it would be a good idea to have a chapter that directly addressed the genetics and genomics of Eco-Evolutionary Dynamics.
While I was preparing the chapter, I received an invitation to submit a review paper to Heredity and decided to convert the developing chapter into that review (it will also appear in the book). The paper was published a few weeks ago. One topic is the few-large versus many-small debate summarized above as an example and the others are summarized in the paper's abstract:
Increasing acceptance that evolution can be ‘rapid’ (or ‘contemporary’) has generated growing interest in the consequences for ecology. The genetics and genomics of these ‘eco-evolutionary dynamics’ will be—to a large extent—the genetics and genomics of organismal phenotypes. In the hope of stimulating research in this area, I review empirical data from natural populations and draw the following conclusions. (1) Considerable additive genetic variance is present for most traits in most populations. (2) Trait correlations do not consistently oppose selection. (3) Adaptive differences between populations often involve dominance and epistasis. (4) Most adaptation is the result of genes of small-to-modest effect, although (5) some genes certainly have larger effects than the others. (6) Adaptation by independent lineages to similar environments is mostly driven by different alleles/genes. (7) Adaptation to new environments is mostly driven by standing genetic variation, although new mutations can be important in some instances. (8) Adaptation is driven by both structural and regulatory genetic variation, with recent studies emphasizing the latter. (9) The ecological effects of organisms, considered as extended phenotypes, are often heritable. Overall, the study of eco-evolutionary dynamics will benefit from perspectives and approaches that emphasize standing genetic variation in many genes of small-to-modest effect acting across multiple traits and that analyze overall adaptation or ‘fitness’. In addition, increasing attention should be paid to dominance, epistasis and regulatory variation.”
I am confident that these “conclusions” have been (if recent emails are any indication), are being, and will continue to be met with agreement by some and derision by others. I hope that folks will take this posting as an opportunity to provide points and counterpoints on these questions. Have at ‘er. Until then – time to finish the rest of the damn book.
|My Christmas haircut from the 70s: an attempted mash-up of the 1870s (beard) and 1970s (hair).|
Hendry, A.P. 2013. Key questions in the genetics and genomics of eco-evolutionary dynamics. Heredity 111:456-466. PDF
A related book chapter that Rowan Barrett and I published last year:
Barrett, R.D.H., and A.P. Hendry. 2012. Evolutionary rescue under environmental change? Pages 216-233 in U. Candolin and B.B.M. Wong (editors). Behavioural responses to a changing world: mechanisms and consequences. Oxford Univ. Press, Oxford, UK. PDF
An early many-small versus few-large post on this blog: Fisher is dead, long live Fisher
And, yes, the title is a parody of Epic Rap Battles of History.
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