The cost of sight is the loss of smell

WHICH is more difficult to do without - vision or smell? If forced to choose, most people would rather keep their sight than their smell for the obvious richness that vision imparts in our everyday lives. Not surprisingly then, is the recent observation that an improvement in human vision appears to have evolved in parallel with a reduction in the human sense of smell.

Structure and function are tightly related phenomena of the biological world. Together, structure and function govern virtually all aspects of life - from the molecular architecture of DNA to the daily search for food played out on the plains of the African Serengeti.
A
n obvious example of this structure and function partnership may be observed in comparing the physiology of mammalian prey and predators.
In prey, such as zebra and gazelles, their eyes on either side of the skull allow for an expanded view of their surroundings. For such prey, it is important to know at all times where their predators are.
In predators such as large cats, their eyes face forward enabling binocular vision to fix and track the moving zebra or gazelle.
Binocular vision has played a particularly important role in developing evolution's most successful predator: man himself.

The sense of sight has been a critical factor in the evolution of hominid species; of the five senses, sight has probably impacted most upon human evolution. However, the present capabilities of the human eye have come at a cost; this cost, as reported in recent molecular genetic studies, appears to be a parallel diminution in the sensitivity of smell.
Of course, when one stops to consider the observation, it is quite obvious that the technological advancements of tool making, social organisation and planning inevitably confer a higher degree of control over one's natural environment.

For instance the transition from nomadic existence to a more settled agriculture lifestyle would predictably throw up quite different selection pressures. In the relative safety of a well organised village the ability to smell a creeping leopard at 400 yards is not as beneficial as being able to distinguish good seeds or fruit from bad ones. Now however, researchers have gained a molecular insight into the actual nuts and bolts of how smell, or "olfaction", has diminished by using the mountains of data generated over the past 10 years from gene sequencing projects of humans and other animals.

Pseudogene scrapheap
The chief tools used by researchers in unravelling this story are special genes known as "pseudogenes". Pseudogenes are essentially dead genes or relics not unlike previous drafts of this article. In fact, like previous drafts of this article, pseudogenes never see the light of day. Pseudogenes are never expressed into proteins. They never make it past the editors red pen and so never enjoy the privilege of being included in a Eurotimes issue.

Real genes, like a finished Eurotimes article, contain an introduction, paragraphs and grammar allowing the reader to know where the article begins and ends. By contrast, pseudogenes have no "introduction," "paragraphs," or appropriate "grammar"; as a result, they are never used by the cell to make a protein.
Because pseudogenes are never expressed into functional proteins, they are not subjected to the natural selection forces that operate on "real" genes.

For instance, if a "real" gene that encodes a critical enzyme of a central pathway becomes mutated and non-functional, then the organism in which that gene mutation has occurred may prematurely die. In other words, natural selection militates against the organism's toleration of that particular gene mutation.
In contrast, a pseudogene that makes no enzymes or proteins may mutate. But as a pseudogene carries out no critical functions there is no negative impact on the organism and so the mutation is maintained and tolerated in subsequent generations.
Pseudogenes can arise in one of two ways: either by duplication of an existing (parental) gene followed by functional inactivation or, by a process of retrotransposition in which mRNA in the cell is converted back into DNA which then inserts into the genome.

Scientists have sifted through enormous volumes of sequence data that are now accessible in a
variety of internet based public domains: www.ensembl.org [for humans]; www.ensembl.org /Mus_musculus [for mice]; http://genome.wustl.edu /projects/chimp/ [for chimps ]. Such data indicates that pseudogenes are relatively common. In fact, some estimates suggest there may be more than 20,000 pseudogenes in the human genome, almost rivalling the 30,000 or so "real" genes identified to date.

Although these pseudogenes are useless in a functional biological sense, they have been put to work on the academic research front in a number of innovative ways. Because pseudogenes can accumulate mutations in a benign fashion - there is no functional consequence to their mutations - scientists can examine the number and types of mutations found in pseudogenes and compare these statistics with the parental gene.

For example, if we pick one parental gene and its pseudogene we can estimate how long ago the pseudogene arose by simply counting the number of differences between the parent gene and the pseudogene. A large difference between the gene and pseudogene would suggest that the pseudogene occurred earlier in evolutionary time; a pseudogene with very few differences between it and its parent gene would suggest a more recent genesis. In other words, pseudogenes can act as molecular clocks that permit scientists to estimate when major genomic events occurred.

Furthermore, it is now possible to examine the pseudogenes of other species, including our closest relatives such as the chimpanzees and bonobos, the great apes and the orangutans. Comparing statistics on parent genes and pseudogenes in these different species can reveal very interesting pictures of how and when these species were related and eventually diverged from each other. It is precisely this type of study - by a graduate student, Yoav Gilad, at the Weizmann Institute of Science, in Rehovot, Israel - that has recently put some hard numbers on this unfolding story.

The Israeli research project looked at a family of genes responsible for smell in humans. The genes, known as olfactory receptors, belong to the 7 transmembrane G protein coupled receptor superfamily, similar to rhodopsin, the light sensitive molecule of the retina responsible for initiating the biochemical visual transduction cascade. These receptors are expressed at the surface of cilia on olfactory sensory neurons located in the olfactory epithelium of the nasal cavity.

Redundant olfactory genes
There are over 1,000 genes in the olfactory receptor (OR) gene family. In humans, more than 60% of these genes are pseudogenes. In contrast, the mouse has a comparable number of OR genes but only approximately 20% of the mouse OR gene repertoire are pseudogenes.

In general, the ratio of OR genes to OR pseudogenes reveals important information on the lifestyle of the animal under study. Predators at the top of the food chain have more OR pseudogenes than OR genes whereas the opposite is the case among prey as you move down the food chain. From such findings, the authors of the Israeli study concluded that the reduced number of functioning OR genes is likely to be a consequence of a reduced dependency on olfaction relative to other species.

In their study, the research team at the Weizmann Institute compared a randomly chosen set of 50 OR genes in humans, chimpanzees, gorillas, orangutans and rhesus monkeys. The 50 OR genes were located on 14 different chromosomes and belonged to 13 different OR gene families. Following the laborious task of sequencing these genes at the lab bench, the researchers then fed the resulting sequence into computers to crunch all the data and extract some meaningful pictures.
The number-crunching determined that the proportion of pseudogenes to genes in the apes and the rhesus macaque monkeys was between 28% and 36%; that was more than the mouse's humble 20%, but less than the human's 54%. The results make for a compelling table:

Analysis of the data - processed by standard computer algorithms freely available from the US National Centre for Biotechnology Information (available at
http://www.ncbi.nlm.nih.gov/ - revealed that although the rate of OR gene disruption for all non-human primates was essentially identical, the rate of OR gene disruption in humans was about 4.3 times greater than the mean. Humans turn out to have accumulated OR pseudogenes at a far faster rate than all the other species examined. When the data from mice, primates and humans was compared directly, the rate of OR gene disruption in mice was approximately half that found in primates and nearly nine times lower than that found in humans.

So what does all this mean? Clearly, humans are far less reliant on their sense of smell than are other primates or mice. As trichromatic colour vision evolved to provide better sight, presumably there was less of a reliance on smell. Given that more genes mean more opportunities for more things to go wrong, natural selection eliminated part of the human olfactory repertoire.

A further observation strengthens this conclusion: one species of New World monkey, the howler monkey, loses OR genes at a similar rate to that observed in the Old World monkeys. Most New World monkeys are very much reliant on smell but the howler monkey is not; however, most interestingly, it is unique in its possession of trichromatic colour vision. In other words, it fits into the model of the link between increased visual acuity and reduced olfactory sensitivity.

Finally, the OR pseudogene observations provide a wonderful window on evolution in progress. Similar to the data being gathered through whole genome comparisons of humans, chimps, mice and flies, the OR pseudogene studies formally and quantifiably confirm what Darwin had postulated in 1859: that species descend through modification.

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