Molecular evolution and structure-function relationships of gene products from extinct and extant mammalian species

脊椎动物血红蛋白直接将外部环境条件与细胞代谢过程联系起来，精心定制，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(氧结合的位置)是相同的，但球蛋白的组成在物种之间可能有很大的差异。氨基酸组成看起来很小的变化，由于碱基与珠蛋白链的DNA替换而产生，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。这些变化无疑在哺乳动物占据不同栖息地的能力方面发挥了关键作用，但人们对它们的确切分子机制和进化模式知之甚少。这项申请是为了资助对灭绝和现存哺乳动物的血红蛋白的新研究，这些研究专门针对北极、半水生和地下环境中的生命，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 with 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 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 extinct and extant mammals specialized to life in arctic, semi-aquatic and subterranean environments, 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).