Digital Commons Network^™

Time Domains Of Hypoxia Responses And -Omics Insights, James J. Yu, Amy L. Non, Erica C. Heinrich, Wanjun Gu, Joe Alcock, Esteban A. Moya, Elijah S. Lawrence, Michael S. Tift, Katie A. O'Brien, Jay F. Storz, Anthony V. Signore, Jane I. Khudyakov, William K. Milsom, Sean M. Wilson, Cynthia M. Beall, Francisco C. Villafuerte, Tsering Stobdan, Colleen G. Julian, Lorna G. Moore, Mark M. Fuster, Jennifer A. Stokes, Richard Milner, John B. West, Jiao Zhang, John Y. Shyy, Ainash Childebayeva, José Pablo Vázquez-Medina, Luu V. Pham, Omar A. Mesarwi, James E. Hall, Zachary A. Cheviron, Jeremy Sieker, Arlin B. Blood, Jason X. Yuan, Tatum S. Simonson, Et Al.

School of Biological Sciences: Faculty Publications

The ability to respond rapidly to changes in oxygen tension is critical for many forms of life. Challenges to oxygen homeostasis, specifically in the contexts of evolutionary biology and biomedicine, provide important insights into mechanisms of hypoxia adaptation and tolerance. Here we synthesize findings across varying time domains of hypoxia in terms of oxygen delivery, ranging from early animal to modern human evolution and examine the potential impacts of environmental and clinical challenges through emerging multi-omics approaches. We discuss how diverse animal species have adapted to hypoxic environments, how humans vary in their responses to hypoxia (i.e., in the context …

Within- And Trans-Generational Environmental Adaptation To Climate Change: Perspectives And New Challenges, Naim M. Bautista, Amélie Crespel

School of Biological Sciences: Faculty Publications

The current and projected impacts of climate change are shaped by unprecedented rates of change in environmental conditions. These changes likely mismatch the existing coping capacities of organisms within-generations and impose challenges for population resilience across generations. To better understand the impacts of projected scenarios of climate change on organismal fitness and population maintenance, it is crucial to consider and integrate the proximate sources of variability of plastic and adaptive responses to environmental change in future empirical approaches. Here we explore the implications of considering: (a) the variability in different time-scale events of climate change; (b) the variability in plastic …

Life Ascending: Mechanism And Process In Physiological Adaptation To High-Altitude Hypoxia, Jay F. Storz, Graham R. Scott

School of Biological Sciences: Faculty Publications

To cope with the reduced availability of O2 at high altitude, air-breathing vertebrates have evolved myriad adjustments in the cardiorespiratory system to match tissue O2 delivery with metabolic O2 demand. We explain how changes at interacting steps of the O2 transport pathway contribute to plastic and evolved changes in whole-animal aerobic performance under hypoxia. In vertebrates native to high altitude, enhancements of aerobic performance under hypoxia are attributable to a combination of environ- mentally induced and evolved changes in multiple steps of the pathway. Additionally, evidence suggests that many high-altitude natives have evolved mechanisms for attenuating maladaptive acclimatization responses to …

Intraspecific Polymorphism, Interspecific Divergence, And The Origins Of Function-Altering Mutations In Deer Mouse Hemoglobin, Chandrasekhar Natarajan, Federico G. Hoffmann, Hayley C. Lanier, Cole J. Wolf, Zachary A. Cheviron, Matthew L. Spangler, Roy E. Weber, Angela Fago, Jay F. Storz

School of Biological Sciences: Faculty Publications

Major challenges for illuminating the genetic basis of phenotypic evolution are to identify causative mutations, to quantify their functional effects, to trace their origins as new or preexisting variants, and to assess the manner in which segregating variation is transduced into species differences. Here, we report an experimental analysis of genetic variation in hemoglobin (Hb) function within and among species of Peromyscus mice that are native to different elevations. A multilocus survey of sequence variation in the duplicated HBA and HBB genes in Peromyscus maniculatus revealed that function-altering amino acid variants are widely shared among geographically disparate populations

from different …

Epistasis Constrains Mutational Pathways Of Hemoglobin Adaptation In High-Altitude Pikas, Danielle M. Tufts, Chandrasekhar Natarajan, Inge G. Revsbech, Joana Projecto- Garcia, Federico G. Hoffmann, Roy E. Weber, Angela Fago, Hideaki Moriyama, Jay F. Storz

School of Biological Sciences: Faculty Publications

A fundamental question in evolutionary genetics concerns the roles of mutational pleiotropy and epistasis in shaping trajectories of protein evolution. This question can be addressed most directly by using site-directed mutagenesis to explore the mutational landscape of protein function in experimentally defined regions of sequence space. Here, we evaluate how pleiotropic trade-offs and epistatic interactions influence the accessibility of alternative mutational pathways during the adaptive evolution of hemoglobin (Hb) function in high-altitude pikas (Mammalia: Lagomorpha). By combining ancestral protein resurrection with a combinatorial protein-engineering approach, we examined the functional effects of sequential mutational steps in all possible pathways that produced …