Abstract
Brain size varies substantially across the animal kingdom and is often associated with cognitive ability; however, the genetic architecture underpinning natural variation in these key traits is virtually unknown. In order to identify the genetic architecture and loci underlying variation in brain size, we analysed both coding sequence and expression for all the loci expressed in the telencephalon in replicate populations of guppies (Poecilia reticulata) artificially selected for large and small relative brain size. A single gene, Angiopoietin-1 (Ang-1), a regulator of angiogenesis and suspected driver of neural development, was differentially expressed between large- and small-brain populations. Zebra fish (Danio rerio) morphants showed that mild knock down of Ang-1 produces a small-brained phenotype that could be rescued with Ang-1 mRNA. Translation inhibition of Ang-1 resulted in smaller brains in larvae and increased expression of Notch-1, which regulates differentiation of neural stem cells. In situ analysis of newborn large- and small-brained guppies revealed matching expression patterns of Ang-1 and Notch-1 to those observed in zebrafish larvae. Taken together, our results suggest that the genetic architecture affecting brain size in our population may be surprisingly simple, and Ang-1 may be a potentially important locus in the evolution of vertebrate brain size and cognitive ability.
Highlights
Vertebrate brain size is remarkably variable at all taxonomic levels
Comparative studies across a range of taxa [3,4,5,6] support the link between brain size and cognitive performance, and the human lineage is distinguished in large part by a dramatic increase in relative brain size and cognitive ability [7]
Despite the widespread interest in brain size and cognition, identifying the targets and mechanisms of selection underlying the evolution of vertebrate brain size and function has proved difficult, and little is known about the genetic basis of variation in relative brain size and cognitive ability [8]
Summary
Vertebrate brain size is remarkably variable at all taxonomic levels. This variation has been proposed to be generated through the balance between positive selection for cognitive ability and the energetic costs of developing and maintaining a larger brain [1,2]. The rapid convergent response in brain size and cognitive ability observed in each replicate population across just a few generations indicates that standing genetic variation, rather than de novo mutation, was the target of artificial selection in these selection lines. To investigate the genetic architecture behind guppy brain size variation, we first used full genome expression analysis of adults of the large- and small-brained guppy selection lines. We compared our results from zebrafish larvae with in situ hybridization analysis of candidate genes in newborn guppies with different brain size. We constructed one pool for each sex for each selection line in order to differentiate any gene expression differences that were the product of genetic drift or founder effects within single selected populations from convergent changes underlying brain size across replicates. We analysed relative brain size using an ANCOVA with brain size as dependent variable, body size as covariate and treatment group as factors, followed by a post hoc LSD test (SPSS 13.0 software package, SPSS Inc.)
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