BIOGEOGRAPHY, INTERSPECIFIC INTROGRESSION, AND THE EVOLUTION OF HEMOGLOBIN GENES IN THE HIGH ANDES: THE EVOLUTIONARY HISTORY OF THE SOUTH AMERICAN SISKINS (Spinus)

Landscape features, interspecific introgression, and adaptation work in concert to shape the evolutionary history of a clade. Understanding the independent and cumulative consequences of these evolutionary processes on diversification is critical to revealing the origins of extant biodiversity. Studying these processes within rapid radiations, a significant contributor to global biodiversity, can provide powerful insight into the process of diversification. To assess how diversification is shaped by these evolutionary forces, I examined the biogeographic history, patterns of interspecific introgression and adaptation to high elevation in a recent, rapid radiation of finches, the South American siskins (Fringillidae: Spinus). I found that this continental radiation colonized South America from North America and subsequently diversified at an exceptional rate in the high Andes. Further, my results show that sympatric siskin species within the high Andes form a monophyletic clade. I hypothesized that the close proximity of near relatives at high elevation could challenge species limits in Spinus. I investigated this hypothesis using a genome-wide SNP dataset to construct phylogenetic trees and performed formal tests of introgression among high elevation species. I developed an approach for assessing introgression despite persistent phylogenetic uncertainty, and discovered evidence for multiple introgressive events among different high elevation Spinus species. Cold temperatures and decreased partial pressure of oxygen are chronic stressors on organisms living at high elevation. Finally, to understand the consequences of high elevation on adaptive divergence in Spinus , I sequenced all genes which encode the oxygen-transport protein hemoglobin across the Spinus clade and among several populations of a species with a wide elevational range. I identified multiple instances of non-synonymous mutations at the inter- and intra-specific level in both adult and embryonic hemoglobin proteins. These patterns of genetic variation within functionally significant loci across elevation suggest that hemoglobin genes have had a significant impact on adaptation and potentially diversification within the South American siskins

Endothelial dysfunction in a murine model of mild hyperhomocyst(e)inemia

Homocysteine is a risk factor for the development of atherosclerosis and its thrombotic complications. We have employed an animal model to explore the hypothesis that an increase in reactive oxygen species and a subsequent loss of nitric oxide bioactivity contribute to endothelial dysfunction in mild hyperhomocysteinemia. We examined endothelial function and in vivo oxidant burden in mice heterozygous for a deletion in the cystathionine β-synthase (CBS) gene, by studying isolated, precontracted aortic rings and mesenteric arterioles in situ. CBS(–/+) mice demonstrated impaired acetylcholine-induced aortic relaxation and a paradoxical vasoconstriction of mesenteric microvessels in response to superfusion of methacholine and bradykinin. Cyclic GMP accumulation following acetylcholine treatment was also impaired in isolated aortic segments from CBS(–/+) mice, but aortic relaxation and mesenteric arteriolar dilation in response to sodium nitroprusside were similar to wild-type. Plasma levels of 8-epi-PGF(2α) (8-IP) were somewhat increased in CBS(–/+) mice, but liver levels of 8-IP and phospholipid hydroperoxides, another marker of oxidative stress, were normal. Aortic tissue from CBS(–/+) mice also demonstrated greater superoxide production and greater immunostaining for 3-nitrotyrosine, particularly on the endothelial surface. Importantly, endothelial dysfunction appears early in CBS(–/+) mice in the absence of structural arterial abnormalities. Hence, mild hyperhomocysteinemia due to reduced CBS expression impairs endothelium-dependent vasodilation, likely due to impaired nitric oxide bioactivity, and increased oxidative stress apparently contributes to inactivating nitric oxide in chronic, mild hyperhomocysteinemia