Abstract
BackgroundThe majority of DNA contained within vertebrate genomes is non-coding, with a certain proportion of this thought to play regulatory roles during development. Conserved Non-coding Elements (CNEs) are an abundant group of putative regulatory sequences that are highly conserved across divergent groups and thus assumed to be under strong selective constraint. Many CNEs may contain regulatory factor binding sites, and their frequent spatial association with key developmental genes – such as those regulating sensory system development – suggests crucial roles in regulating gene expression and cellular patterning. Yet surprisingly little is known about the molecular evolution of CNEs across diverse mammalian taxa or their role in specific phenotypic adaptations. We examined 3,110 vertebrate-specific and ~82,000 mammalian-specific CNEs across 19 and 9 mammalian orders respectively, and tested for changes in the rate of evolution of CNEs located in the proximity of genes underlying the development or functioning of auditory systems. As we focused on CNEs putatively associated with genes underlying the development/functioning of auditory systems, we incorporated echolocating taxa in our dataset because of their highly specialised and derived auditory systems.ResultsPhylogenetic reconstructions of concatenated CNEs broadly recovered accepted mammal relationships despite high levels of sequence conservation. We found that CNE substitution rates were highest in rodents and lowest in primates, consistent with previous findings. Comparisons of CNE substitution rates from several genomic regions containing genes linked to auditory system development and hearing revealed differences between echolocating and non-echolocating taxa. Wider taxonomic sampling of four CNEs associated with the homeobox genes Hmx2 and Hmx3 – which are required for inner ear development – revealed family-wise variation across diverse bat species. Specifically within one family of echolocating bats that utilise frequency-modulated echolocation calls varying widely in frequency and intensity high levels of sequence divergence were found.ConclusionsLevels of selective constraint acting on CNEs differed both across genomic locations and taxa, with observed variation in substitution rates of CNEs among bat species. More work is needed to determine whether this variation can be linked to echolocation, and wider taxonomic sampling is necessary to fully document levels of conservation in CNEs across diverse taxa.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-014-0261-5) contains supplementary material, which is available to authorized users.
Highlights
The majority of DNA contained within vertebrate genomes is non-coding, with a certain proportion of this thought to play regulatory roles during development
Study of coding Elements (CNEs) in the Hmx2/3 gene region of echolocating taxa Given the observed variation in the substitution rate of the Hmx2/3 gene region across echolocating bats and the bottlenose dolphin, we looked more closely at sequence variation in CNEs located in this genomic region in a wider range of bat and cetacean species for which published genomes are available with a variety of echolocation call types
We found evidence for significantly greater substitution rates in all six bat species compared to the horse in vertebrate specific CNEs from two genomic regions (SHH and TSHZ1)
Summary
The majority of DNA contained within vertebrate genomes is non-coding, with a certain proportion of this thought to play regulatory roles during development. Conserved Non-coding Elements (CNEs) are an abundant group of putative regulatory sequences that are highly conserved across divergent groups and assumed to be under strong selective constraint. Surprisingly little is known about the molecular evolution of CNEs across diverse mammalian taxa or their role in specific phenotypic adaptations. Many Conserved Non-coding Elements (CNEs) are likely candidates for regulatory regions of gene expression [1]. Recent evidence from Highland cattle (Bos taurus) and ‘fancy’ rats (Rattus norvegicus), have linked mutations in a conserved genomic region proximate to Hmx to abnormal pinna development [9,10]. It appears that the selective constraints acting on CNEs vary across different taxa, and that different genomic regions may all contribute differentially to the overall phenotype of an organism
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