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Comparative Study
.2003 Mar 18;100(6):3324-7.
doi: 10.1073/pnas.0535697100. Epub 2003 Feb 28.

Human specific loss of olfactory receptor genes

Affiliations
Comparative Study

Human specific loss of olfactory receptor genes

Yoav Gilad et al. Proc Natl Acad Sci U S A..

Abstract

Olfactory receptor (OR) genes constitute the basis for the sense of smell and are encoded by the largest mammalian gene superfamily of >1,000 genes. In humans, >60% of these are pseudogenes. In contrast, the mouse OR repertoire, although of roughly equal size, contains only approximately 20% pseudogenes. We asked whether the high fraction of nonfunctional OR genes is specific to humans or is a common feature of all primates. To this end, we have compared the sequences of 50 human OR coding regions, regardless of their functional annotations, to those of their putative orthologs in chimpanzees, gorillas, orangutans, and rhesus macaques. We found that humans have accumulated mutations that disrupt OR coding regions roughly 4-fold faster than any other species sampled. As a consequence, the fraction of OR pseudogenes in humans is almost twice as high as in the non-human primates, suggesting a human-specific process of OR gene disruption, likely due to a reduced chemosensory dependence relative to apes.

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Figures

Figure 1
Figure 1
A neighbor-joining tree of all human OR loci in the HORDE database. The names of the OR gene families are indicated next to the branches, which represent the majority of members from each subfamily. Few OR members of any subfamily may be dispersed elsewhere in the tree (not specified). The 50 ORs chosen at random for this study are indicated as circles.
Figure 2
Figure 2
OR pseudogene accumulation and DNA sequence divergence in primates. The number of OR pseudogenes inferred to have arisen on each branch is given in red. The inferred divergence (in percentage) for each branch is indicated in blue. Because we used the rhesus as an outgroup, we could not infer the divergence specific to the rhesus lineage. A combined divergence value for the outgroup is indicated by the arrows. We inferred gene silencing events on the rhesus lineage by assuming that the mutations have always occurred to disrupt an intact coding region rather than to reverse a disruption.
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