Question

In most species of mammals, the \(\mathrm{O}_{2}\) affinity of a fetus's blood hemoglobin is greater than that of its mother's blood hemoglobin. However, mammal species are not all the same in the mechanism that causes the affinities to be different. Specify three distinct mechanisms for the difference in affinity between fetal and maternal blood hemoglobin. Recall from Chapter 1 that François Jacob argued that evolution is analogous to tinkering rather than engineering. Considering the mechanism of the fetal- maternal difference in \(\mathrm{O}_{2}\) affinity, would you say that the evolution of the mechanism provides evidence for Jacob's argument? Explain.

Short answer

Three mechanisms for the difference in affinity between fetal and maternal hemoglobin include: difference in protein subunits, different concentration of DPG, and the bohr effect. And these random differences support Jacob's analogy of evolution as 'tinkering' instead of 'engineering'.

Step-by-step solution

Identifying the Mechanism

There are several mechanisms that could explain the noted difference in oxygen affinity of fetal and maternal hemoglobin:1. Difference in the protein subunits that make up fetal and maternal hemoglobins. Fetal hemoglobin (HbF) has a pair of gamma subunits in place of the beta subunits found in adult hemoglobin (HbA). The gamma subunits in HbF interact less with 2,3-Bisphosphoglycerate, a molecule that promotes the release of oxygen, resulting in higher oxygen affinity.2. The fetal hemoglobin has a higher concentration of DPG (2,3-diphosphoglycerate) which binds to maternal hemoglobin and lowers its affinity for oxygen, making it easier for the oxygen to switch from mother to fetus.3. The mechanism of the bohr effect: In the maternal system, there may be lower pH (more acidic) which can decrease the affinity of hemoglobin for oxygen, facilitating its transfer to the fetus.

Analyzing the Evolutionary Aspect

These differences in mechanism doesn't seem to be the result of precise engineering, but rather the random assortment and mutation of previous functional components (the different subunits of hemoglobin). Therefore, it can be argued that this evidence supports Jacob's analogy of evolution as 'tinkering' as opposed to 'engineering'.

Key concepts

Fetal Hemoglobin (HbF)

Imagine a tiny fetus developing in the womb, receiving oxygen not from its own lungs but through the blood supplied by the mother. The key to this vital exchange is fetal hemoglobin (HbF), a special type of hemoglobin that binds oxygen more tightly than the adult form. This higher affinity is crucial for extracting oxygen from the maternal blood.

Unlike adults whose hemoglobin contains two alpha and two beta protein subunits, HbF has two alpha and two gamma subunits. These gamma subunits change the hemoglobin’s structure, making it less inclined to bind with 2,3-Bisphosphoglycerate (2,3-BPG), a compound that typically decreases oxygen affinity in adult hemoglobin (HbA). Consequently, HbF can hang onto oxygen with a firmer grip, ensuring that the developing fetus receives sufficient oxygen for growth.

2,3-Bisphosphoglycerate (2,3-BPG)

A key player in oxygen exchange is the molecule 2,3-BPG. Found abundantly in red blood cells, it diligently performs its role in helping offload oxygen from hemoglobin to the tissues that need it.

In adult hemoglobin (HbA), 2,3-BPG binds to the beta subunits, prompting a release of oxygen. However, fetal hemoglobin (HbF) shows less interaction with 2,3-BPG, favoring oxygen retention. The reason? HbF's gamma subunits are less receptive to 2,3-BPG than the beta subunits in HbA. This helps ensure a high oxygen supply for the fetus but allows adults to efficiently deliver oxygen to their active muscles and organs.

The differentiated response to 2,3-BPG highlights how even small changes in molecular structure can have significant impacts on an organism's overall function.

Bohr Effect

The Bohr effect is a physiological phenomenon where hemoglobin's oxygen binding affinity is inversely related to both acidity and carbon dioxide concentration. Essentially, an increase in carbon dioxide results in a more acidic environment which decreases hemoglobin's affinity for oxygen.

This effect explains how actively metabolizing tissues that produce more CO2 and lower the pH can receive more oxygen from the blood. Maternal blood, carrying the byproducts of metabolism such as CO2, becomes more acidic as it passes through tissues, prompting hemoglobin to release its bound oxygen. This released oxygen can then be picked up by the fetal hemoglobin, which is less affected by the Bohr effect due to its different structure and lower affinity for 2,3-BPG.

Evolution of Hemoglobin

The evolution of hemoglobin serves as a testament to nature's way of 'tinkering'. Over time, incremental changes and adaptations have resulted in various forms of hemoglobin suited to different life stages and species needs.

Fetal hemoglobin is one such example, optimized to ensure efficient oxygen transfer from mother to fetus. Its evolution wasn't a linear path towards a 'perfect' solution, but rather a series of modifications to existing molecules that improved survival. Such a process supports the idea introduced by François Jacob, who postulated evolution as resembling the work of a 'tinkerer' – improvising with the materials at hand, rather than the precise work of an engineer creating from a clean slate.

Protein Subunits in Hemoglobin

Diving deeper into the world of hemoglobin, we find that its functionality is largely due to the composition of its protein subunits. The most common adult hemoglobin, HbA, is comprised of two alpha and two beta subunits.

The structural differences between the subunits dictate the oxygen-carrying behavior of the hemoglobin. The fetal version, HbF, replaces the beta subunits with gamma subunits. This slight alteration in its subunit composition leads to a significant increase in the oxygen affinity of HbF. By understanding the precise role of these protein subunits, medical professionals can even develop treatments for diseases like sickle cell anemia that affect hemoglobin's ability to carry oxygen.