The Molecular Basis of High-Altitude Adaptation in Deer Mice

Abstract

Elucidating genetic mechanisms of adaptation is a goal of central importance in evolutionary biology, yet few empirical studies have succeeded in documenting causal links between molecular variation and organismal fitness in natural populations. Here we report a population genetic analysis of a two-locus α-globin polymorphism that underlies physiological adaptation to high-altitude hypoxia in natural populations of deer mice, Peromyscus maniculatus. This system provides a rare opportunity to examine the molecular underpinnings of fitness-related variation in protein function that can be related to a well-defined selection pressure. We surveyed DNA sequence variation in the duplicated α-globin genes of P. maniculatus from high- and low-altitude localities (i) to identify the specific mutations that may be responsible for the divergent fine-tuning of hemoglobin function and (ii) to test whether the genes exhibit the expected signature of diversifying selection between populations that inhabit different elevational zones. Results demonstrate that functionally distinct protein alleles are maintained as a long-term balanced polymorphism and that adaptive modifications of hemoglobin function are produced by the independent or joint effects of five amino acid mutations that modulate oxygen-binding affinity.

The in-vivo oxyhaemoglobin dissociation curve at sea level and high altitude

“…Animals native to high altitude (such as llamas and yaks), but not animals that have recently been introduced to high altitude (such as sheep and cows), exhibit high haemoglobin affinity (Beall, 2007a) that is retained, to a large extent, when they are taken lower altitudes. Increased affinity has been achieved by changes in haemoglobin structure, as in deer mice in the Rocky Mountains (Storz et al, 2007) and high altitude chickens that were introduced to the Andes only 500 years ago (Velarde et al, 1991). Alternatively, it has also been achieved by a decrease in [2,, as in Tibetan pika (Ge et al, 1998), or by decreased influence of 2,3-DPG, as in bar-headed geese (Petschow et al, 1977).…”

Advances and limits of using population genetics to understand local adaptation

“…coat color in mice [6,7], flowering time in annual plants [8], immunity in plants and animals, [9,10], high altitude adaptation [11]). These studies have targeted traits already thought to have been targets of local adaptation.…”

Relaxed functional constraints on triplicate α-globin gene in the bank vole suggest a different evolutionary history from other rodents

“…To amplify the a-globin genes from genomic DNA in the bank vole, we used published sets of PCR primers originally designed to amplify selectively the individual paralogous a-globin genes in Mus (Storz et al, 2007b) and in Peromyscus (Storz et al, 2007a). However, only the primer pair designed to selectively amplify the HBA-T2 gene in Peromyscus (D-1518 and D-2387R; Storz et al, 2007a) yielded a specific PCR product in the bank vole.…”

“…However, only the primer pair designed to selectively amplify the HBA-T2 gene in Peromyscus (D-1518 and D-2387R; Storz et al, 2007a) yielded a specific PCR product in the bank vole. Therefore, to isolate any other a-globin genes from this species, we cloned and sequenced bank vole globin complementary DNA (cDNA).…”

“…The primers were selected to match sequences of the 5 0 and 3 0 untranslated regions (UTRs) that allowed each gene to be amplified and sequenced from initiation to termination codon. Two new forward primers (5 0 -ACACACTTCTGATTCT-GAGA-3 0 and 5 0 -CGGACTCAGGAAGGAATTCAT-3 0 ) were used in combinations with the primer D-2387R (Storz et al, 2007a) to amplify the HBA-T1 and HBA-T3 genes, respectively. Each PCR (total volume of 25 ml) contained 2.5 units of Easy-A high-fidelity PCR cloning enzyme (Agilent Technologies, La Jolla, CA, USA), 2.5 ml of 10 Â Easy-A reaction buffer, 0.2 mM dNTP and 0.3 mM primers.…”