Molecular evolution & functional characterization of gene products from extinct and extant mammalian species

将外部环境条件与细胞代谢过程直接联系起来，脊椎动物血红蛋白是精心定制的，以平衡肺部的氧气摄取及其向组织的输送。虽然所有血红蛋白的血红素基团（氧结合位点）是相同的，但珠蛋白的组成在物种之间可以有很大的差异。由珠蛋白链DNA内的碱基替换引起的氨基酸组成的看似微小的变化，可以对蛋白质的氧结合特性和对温度的敏感性产生深远的影响。这些改变无疑在鸟类和哺乳动物占据各种栖息地的能力中发挥了关键作用，但对其精确的分子机制和进化模式知之甚少。这项申请是为了资助对血红蛋白的新研究，这些血红蛋白来自小型和大型，灭绝和现存的鸟类和哺乳动物，专门生活在北极，半水生和地下环境中，并特别关注这些呼吸蛋白对温度和其他红细胞配体（二氧化碳，质子，氯离子和某些有机磷酸盐）的氧结合特性。

Directly linking external environmental conditions with cellular metabolic processes, vertebrate hemoglobins are exquisitely tailored to balance the uptake of oxygen at the lungs and its delivery to the tissues. While the heme groups (the loci for oxygen binding) of all hemoglobins are identical, the globin composition can vary substantially between species. Seemingly small changes in the amino acid composition, resulting from base substitutions within the DNA of the globin chains, can have profound effects on the protein's oxygen-binding characteristics and sensitivity to temperature. These alterations have undoubtedly played a key role in the ability of birds and mammals to occupy a diverse range of habitats, yet little is known regarding their precise molecular mechanisms and mode of evolution. This application is for funds to support novel research on hemoglobins from small and large, extinct and extant birds and mammals specialized to life in Arctic, semi-aquatic and subterranean environments, and focusing specifically on the oxygen binding characteristics of these respiratory proteins in response to temperature and other red cell ligands (carbon dioxide, protons, chloride ions and certain organic phosphates).