Biological complexity: chromosome and how we smell odors (Introduction)

by David Turell , Saturday, January 19, 2019, 00:43 (2136 days ago) @ David Turell

Chromosomes change neurons as part of the process; one odor per neuron:

https://www.nature.com/articles/d41586-019-00010-6

"Mammals can discriminate between a vast number of volatile compounds — perhaps more than a trillion. This extraordinary capacity is encoded by a repertoire of hundreds of olfactory-receptor genes, distributed in small groups that are present on almost all chromosomes2. To ensure that the response to individual odours is specific, each olfactory sensory neuron (OSN) expresses a single, randomly selected olfactory-receptor gene. Writing in Nature, Monahan et al.3 show that, in the nuclei of mouse OSNs, certain regions of multiple chromosomes assemble in a structure that controls the expression of the full repertoire of olfactory-receptor genes in the nose, while making sure that each cell expresses only one type of receptor. These exciting findings show that interchromosomal interactions can have a determinant role in regulating gene expression.

"The expression of vertebrate genes is regulated by activating genomic elements called enhancers. Enhancers can be located far from the genes themselves4, but they are typically present on the same chromosome as the gene they regulate (cis interactions). These regulatory interactions are mediated by transcription factors, assisted by other proteins, and require the participating proteins and DNA elements to be closely connected in the nucleus.

"Molecular techniques, such as Hi-C5, that capture the 3D folding of chromatin (DNA and associated proteins) have revealed that the interactions between genes and their enhancers occur in compact structures called topologically associating domains (TADs) that organize chromosomes into distinct cis neighbourhoods6. Hi-C analyses have also uncovered specific interactions between genes and genomic elements located much farther away from each other, in different TADs and even on different chromosomes (these are called trans interactions)

***

"why would olfactory-receptor genes require such a large number of elements to regulate their expression, whereas most other genes need only a few? One possibility is that the transition of olfactory-receptor genes from a repressed, heterochromatic state to an active state requires many LHX2 binding sites to ensure that enough chromatin-remodelling proteins, which are necessary for this transition, are recruited. Alternatively, the use of ‘weak’ enhancers that only function as activators collectively might limit the possibility that more than one olfactory-receptor gene is expressed in a cell, and also avoid favouring the expression of olfactory-receptor genes close to ‘strong’ enhancers. The principle underlying this mechanism would be similar to the use of transcription-factor binding sites that have low or modest affinity at enhancers to achieve specificity of gene expression.

***

"It remains unclear whether interchromosomal interactions similar to those displayed by olfactory-receptor genes in OSNs occur frequently between other genomic regions in other cell types, although trans interactions have been reported in a few other cases of stochastic regulation of gene expression15,16. Interchromosomal interactions might therefore be primarily a mechanism for generating diversity in a population of otherwise indistinguishable cells. Because their characteristic signatures are masked by cell-population averages, these cases are difficult to identify. The development and improvement of techniques for analysing gene expression and chromatin conformation in single cells might, in the near future, reveal new examples of 3D genomic structures and functional trans-regulatory interactions."

Comment: The obvious reason for the complexity is our ability to distinguish each odor as learned by memory with every new encounter and keep the recognitions separate and pure. What is the real question is how did this evolve? Were the variety of odors minimal in early mammalian life so the mechanism could develop bit by bit? Or perhaps, more reasonably, was this all designed from the beginning?