Freethought & Rationalism Archive

scigirl · 01-16-2003, 07:54 AM

So I learned the other day in neuro class that humans have several pseudogenes for certain odor receptors. These same genes are found in mice, but less of them are inactive in mice. Hmm, that look suspicious doesn't it...

The human olfactory receptor repertoire.

Quote:

BACKGROUND: The mammalian olfactory apparatus is able to recognize and distinguish thousands of structurally diverse volatile chemicals. This chemosensory function is mediated by a very large family of seven-transmembrane olfactory (odorant) receptors encoded by approximately 1,000 genes, the majority of which are believed to be pseudogenes in humans. ...We report here the identification and physical cloning of 347 putative human full-length odorant receptor genes. Comparative sequence analysis of the predicted gene products allowed us to identify and define a number of consensus sequence motifs and structural features of this vast family of receptors...We believe that these sequences represent the essentially complete repertoire of functional human odorant receptors. CONCLUSIONS: The identification and cloning of all functional human odorant receptor genes is an important initial step in understanding receptor-ligand specificity and combinatorial encoding of odorant stimuli in human olfaction.

So what are those pseudogenes doing in humans, if they aren't simply remnants of evolution?

Different evolutionary processes shaped the mouse and human olfactory receptor gene families.

Quote:

We report a comprehensive comparative analysis of human and mouse olfactory receptor (OR) genes. The OR family is the largest mammalian gene family known. We identify approximately 93% of an estimated 1500 mouse ORs, exceeding previous estimates and the number of human ORs by 50%. Only 20% are pseudogenes, giving a functional OR repertoire in mice that is three times larger than that of human. The proteins encoded by intact human ORs are less highly conserved than those of mouse, in patterns that suggest that even some apparently intact human OR genes may encode non-functional proteins. Mouse ORs are clustered in 46 genomic locations, compared to a much more dispersed pattern in human. We find orthologous clusters at syntenic human locations for most mouse genes, indicating that most OR gene clusters predate primate-rodent divergence. However, many recent local OR duplications in both genomes obscure one-to-one orthologous relationships, thereby complicating cross-species inferences about OR-ligand interactions. Local duplications are the major force shaping the gene family. Recent interchromosomal duplications of ORs have also occurred, but much more frequently in human than in mouse. In addition to clarifying the evolutionary forces shaping this gene family, our study provides the basis for functional studies of the transcriptional regulation and ligand-binding capabilities of the OR gene family.

A gene recently inactivated in human defines a new olfactory receptor family in mammals.

Quote:

...We previously demonstrated that a high fraction of human OR sequences have incurred deleterious mutations, thus reducing the repertoire of functional OR genes. In this study, we have characterized a new OR gene, 912-93, in primates. This gene is unique and it defines a new OR family. It localizes to human chromosome 11q11-12 and at syntenical sites in other hominoids. The sequence marks a previously unrecognized rearrangement of pericentromeric material from chromosome 11 to the centromeric region of gibbon chromosome 5. The human gene contains a nonsense point mutation in the region corresponding to the extracellular N-terminus of the receptor. This mutation is present in humans of various ethnic groups, but is absent in apes, suggesting that it probably appeared during the divergence of humans from other apes, <4 000 000-5 000 000 years ago. A second mutation, a frameshift at a different location, has occurred in the gorilla copy of this gene. These observations suggest that OR 912-93 has been recently silenced in human and gorilla, adding to a pool of OR pseudogenes whose growth may parallel a reduction in the sense of smell in primates.

Hmm, a gene that occurs in primates, its mutation correlates with our evolutionary trees, and in part explains some of the differences between primates and their ancestors.

Wow, that pesky evilution with all its data...

scigirl

KnightWhoSaysNi · 01-16-2003, 03:21 PM

Good post scigirl.

Creationists will definitely not like the 'smell' of it.

This is just like the pseudogene for Vit. C synthesis.

theyeti · 01-16-2003, 03:34 PM

Yes, very good! One thing I think that gets lost on creationists/IDists who try to downplay the issue of pseudogenes is just how big the problem is from their perspective. In the human genome, pseudogenes outnumber functioning genes by about 7 to 1 IIRC.

theyeti

Coragyps · 01-16-2003, 05:07 PM

Somewhere deep in the archives of this forum is a thread on the vomeronasal organ of primates: it connects up closely with this topic, as the VNO is a sense organ that is kind of "smell" in the mouse. It has no proven function in humans or chimps, and there are several pseudogenes associated with it in those species, too.

pz · 01-16-2003, 05:56 PM

Quote:

Originally posted by Coragyps
Somewhere deep in the archives of this forum is a thread on the vomeronasal organ of primates: it connects up closely with this topic, as the VNO is a sense organ that is kind of "smell" in the mouse. It has no proven function in humans or chimps, and there are several pseudogenes associated with it in those species, too.

It does have a function! Luteinizing hormone-releasing hormone (LHRH) neurons are generated in the olfactory placode to migrate along the vomeronasal nerves to reach the hypothalamus. Damage to this region can lead to a loss of these cells, with subsequent deficiencies in the production of essential hormones.

There's a disease called Kallman Syndrome: it's caused by a genetic defect that knocks out a cell adhesion molecule needed for migration of both the LHRH cells and olfactory growth cones. Those afflicted have both anosmia (inability to smell) and hormonal problems...secondary sexual characteristics fail to fully develop at puberty.

So they have no sensory function, but they definitely have a very important developmental function.

Valentine Pontifex · 01-16-2003, 08:20 PM

There was an article on this sometime last year in Natural History by Carl Zimmer. I don't have the citation handy since I read it in the library.

This is also briefly noted in 29+ Evidences For Evolution.

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01-16-2003, 03:21 PM	#2
KnightWhoSaysNi Veteran Member Join Date: Sep 2001 Location: Edmonton, Canada Posts: 2,767	Good post scigirl. Creationists will definitely not like the 'smell' of it. This is just like the pseudogene for Vit. C synthesis.

01-16-2003, 03:34 PM	#3
theyeti Veteran Member Join Date: Jun 2001 Location: Denver, CO, USA Posts: 9,747	Yes, very good! One thing I think that gets lost on creationists/IDists who try to downplay the issue of pseudogenes is just how big the problem is from their perspective. In the human genome, pseudogenes outnumber functioning genes by about 7 to 1 IIRC. theyeti

01-16-2003, 05:07 PM	#4
Coragyps Veteran Join Date: Aug 2001 Location: Snyder,Texas,USA Posts: 4,411	Somewhere deep in the archives of this forum is a thread on the vomeronasal organ of primates: it connects up closely with this topic, as the VNO is a sense organ that is kind of "smell" in the mouse. It has no proven function in humans or chimps, and there are several pseudogenes associated with it in those species, too.

01-16-2003, 08:20 PM	#6
Valentine Pontifex Veteran Member Join Date: Jul 2001 Location: Orion Arm of the Milky Way Galaxy Posts: 3,092	There was an article on this sometime last year in Natural History by Carl Zimmer. I don't have the citation handy since I read it in the library. This is also briefly noted in 29+ Evidences For Evolution.

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