Supplementary Material for: Evolution of the SRGAP2 Gene Is Linked to Intelligence in Mammals

<b><i>Background/Aims:</i></b> A recent duplication of the gene encoding SLIT-ROBO Rho GTPase-activating protein 2 <i>(SRGAP2)</i> in the primate lineage has been proposed to be associated with the human-specific extraordinary development of intelligence. There is no report regarding the role of the <i>SRGAP2</i> gene in the expression of neural traits indicating intelligence in mammals. <b><i>Methods:</i></b> A phylogenetic tree of the <i>SRGAP2 </i>gene from 11 mammals was reconstructed using MrBayes. The evolution of neural traits along the branches of the phylogenetic tree was modeled in the BayesTraits, and the dN/dS ratio (i.e. the ratio between the number of nonsynonymous substitutions per nonsynonymous site and the number of synonymous substitutions per synonymous site) was estimated using the codon-based maximum likelihood method (CODEML) in PAML (phylogenetic analysis by maximum likelihood). <b><i>Results:</i></b> Two neural traits, namely brain mass and the number of cortical neurons, showed statistical dependency on the underlying evolutionary history of the <i>SRGAP2</i> gene in mammals. A significant positive correlation between the increase in cortical neurons and the rate of nucleotide substitutions in the <i>SRGAP2</i> gene was observed concomitantly with a significant negative correlation between the increase in cortical neurons and the rate of nonsynonymous substitutions in the gene. The <i>SRGAP2 </i>gene appears to be under intense pressure of purifying selection in all mammalian lineages under stringent functional constraint. <b><i>Conclusion:</i></b> This work indicates a key role of the <i>SRGAP2</i> gene in the rapid expansion of neurons in the brain cortex, thereby facilitating the evolution of remarkable intelligence in mammals

Supplementary Material for: Correlated Evolution of Gonadotropin-Releasing Hormone and Gonadotropin-Inhibitory Hormone and Their Receptors in Mammals

<b><i>Background:</i></b> Evolutionary rate variation in genes (proteins) is manifested both within the species (genome) and between the species (genomes). However, the interdependent components of a biological system in form of a gene or a protein are expected to evolve in a correlated manner under a common functional constraint. <b><i>Methods:</i></b> The phylogenetic analysis and correlation analysis of gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory hormone (GnIH) and their receptors (GnRHR and GnIHR) was conducted along with other control neuropeptides. <b><i>Results:</i></b> Both neuropeptides and their receptors regulating the reproductive neuroendocrine axis in vertebrates exhibited a correlated evolution under a common physiological constraint to regulate the release of gonadotropin. This result supports a coordinated substitution of amino acids in the GnRH and the GnIH neuropeptides along with their receptors in terms of similar evolutionary rates and distances with similar nucleotide composition of genes. <b><i>Conclusion:</i></b> This is the first demonstration of the correlated evolution of two components of an endocrine system regulating the release of gonadotropin which are acting in concert for successful reproduction