Predictable convergence in hemoglobin function has unpredictable molecular underpinnings

Abstract

To investigate the predictability of genetic adaptation, we examined the molecular basis of convergence in hemoglobin function in comparisons involving 56 avian taxa that have contrasting altitudinal range limits. Convergent increases in hemoglobin-oxygen affinity were pervasive among high-altitude taxa, but few such changes were attributable to parallel amino acid substitutions at key residues. Thus, predictable changes in biochemical phenotype do not have a predictable molecular basis. Experiments involving resurrected ancestral proteins revealed that historical substitutions have context-dependent effects, indicating that possible adaptive solutions are contingent on prior history. Mutations that produce an adaptive change in one species may represent precluded possibilities in other species because of differences in genetic background.

Hemoglobin–oxygen affinity in high-altitude vertebrates: is there evidence for an adaptive trend?

“…For example, birds typically express two main Hb isoforms in definitive red blood cells -a major isoform, HbA, which incorporates α-type products of the α A -globin gene, and a minor isoform, HbD, which incorporates α-type products of the α D -globin gene; the two isoforms share the same β-type subunits Grispo et al, 2012;Opazo et al, 2015). In all bird species that have been examined to date, the minor HbD isoform has an appreciably higher O 2 affinity than the major HbA isoform in the presence of allosteric effectors (Grispo et al, 2012;Projecto-Garcia et al, 2013;Cheviron et al, 2014;Galen et al, 2015;Natarajan et al, 2015bNatarajan et al, , 2016. Other sauropsid taxa also tend to co-express multiple, structurally distinct Hb isoforms in definitive erythrocytes (Weber and Jensen, 1988;Storz et al, 2011bStorz et al, , 2015bDamsgaard et al, 2013).…”

“…5B). These taxa include ground doves, nightjars, hummingbirds, passerines and waterfowl Cheviron et al, 2014;Galen et al, 2015;Natarajan et al, 2015bNatarajan et al, , 2016. In the case of the passerines and waterfowl, we can make comparisons between closely related species as well as conspecific populations.…”

“…As in the case with the mammals, the 29 pairwise comparisons are phylogenetically independent. For information regarding elevational ranges, see Projecto-Garcia et al (2013), Cheviron et al (2014), Galen et al (2015) and Natarajan et al (2015bNatarajan et al ( , 2016.…”

Neutral and functionally important genes shed light on phylogeography and the history of high‐altitude colonization in a widespread New World duck

“…One of the best‐studied examples of genetically based adaptation involves the blood O 2 transport protein hemoglobin. Many organisms native to high altitude exhibit hemoglobin with a high affinity for oxygen (Weber, 2007); in birds, increased hemoglobin‐oxygen affinity has evolved convergently across multiple lineages occurring at high elevations (Natarajan et al., 2016). Studies of hemoglobin have also revealed environmentally induced phenotypic plasticity in response to pressures associated with high elevations.…”

Digest: Know your poison: Predictable molecular changes confer toxin resistance in snakes

“…In the case of Na V 1.4-mediated TTX resistance, Hague et al (2017) suggest that permissible substitutions may be limited, as those that may be beneficial in terms of toxin resistance must also not disrupt the sodium channel's function. Recent molecular studies of functional convergence in the haemoglobin of high-altitude adapted bird species have also highlighted the importance of genetic background and the context-dependent effects of historic mutations (Natarajan et al 2016).…”