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.
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| My Christmas haircut from the 70s: an attempted mash-up of the 1870s (beard) and 1970s (hair). |
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The paper:
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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