Project description:Evolutionary studies are often limited by missing data that are critical to understanding the history of selection. Selection experiments, which reproduce rapid evolution under controlled conditions, are excellent tools to study how genomes evolve under selection. Here we present a genomic dissection of the Longshanks selection experiment, in which mice were selectively bred over 20 generations for longer tibiae relative to body mass, resulting in 13% longer tibiae in two replicates. We synthesized evolutionary theory, genome sequences and molecular genetics to understand the selection response and found that it involved both polygenic adaptation and discrete loci of major effect, with the strongest loci likely to be selected in parallel between replicates. We show that selection may favor de-repression of bone growth through inactivating two limb enhancers of an inhibitor, Nkx3-2. Our integrative genomic analyses thus show that it is possible to connect individual base-pair changes to the overall selection response.
Project description:Evolutionary studies are often limited by missing data that are critical to understanding the history of selection. Selection experiments, which reproduce rapid evolution under controlled conditions, are excellent tools to study how genomes evolve under selection. Here we present a genomic dissection of the Longshanks selection experiment, in which mice were selectively bred over 20 generations for longer tibiae relative to body mass, resulting in 13% longer tibiae in two replicates. We synthesized evolutionary theory, genome sequences and molecular genetics to understand the selection response and found that it involved both polygenic adaptation and discrete loci of major effect, with the strongest loci likely to be selected in parallel between replicates. We show that selection may favor de-repression of bone growth through inactivating two limb enhancers of an inhibitor, Nkx3-2. Our integrative genomic analyses thus show that it is possible to connect individual base-pair changes to the overall selection response.
Project description:This study was undertaken to uncover the molecular pathways that underlie differences among individuals in rates of longitudinal growth and mature length of the long bones in a rodent model. To do so, the transcriptomic profiles of the proximal epiphyses of 14-day old CD-1 wildtype mice and the Longshanks mice were compared. The Longshanks mouse was selectively bred for longer tibiae in relation to body mass (see Marchini et al 2014 – BMC Evol Biol 14:258). Over 13 generations, Longshanks tibiae were 11-12% longer compared to random-bred wildtype mice (hereafter Controls) from the same genetic background (ICR or CD-1), but body mass was unchanged. By comparing the transcriptomes of samples of Control and Longshanks proximal tibiae, we sought to identify differentially expressed genes that were associated with the faster growth and longer tibia of the Longshanks mouse, as a window into the pathways that may underlie intra- and interspecific differences in limb bone size and shape. Results were further validated using qPCR and cell and tissue culture assays.
Project description:Mice deficient for Hdac3 in mesenchymal progenitor cell (under the PRX1 promoter) die perinataly and exhibit severly short limbs. Here we analyzed the differentiational gene expression in the limbs of these mice. We observed that limbs from the CKO mice have higher expression of genes responsible for matrix degradation. In addition, we identified significant upregulation of FGF21 expression in CKO limbs.
Project description:Salamanders completely regenerate their limbs after amputation. Thus, these animals are unique models to investigate the mechanisms modulating the regeneration in vertebrates. To investigate the influence of microRNAs on the newt limb regeneration, an integrative analysis of microRNAome, transcriptome, and proteome were performed.
