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Nose to Nose: Combinatorial Rules for Building a Complex System


Generally, noses don't get as much respect as eyes and ears. However, they are no less remarkable for their sensitivity to a vast number of separate odors. How does an embryo with a small set of precursor neurons build an elaborate, organized system composed of many thousands of specific neurons, all arranged logically and tuned to individual odors? That was the subject of a recent paper in Current Biology, "Combinatorial Rules of Precursor Specification Underlying Olfactory Neuron Diversity."

It's all about coding.

On a fruit fly, olfactory receptor neurons (ORNs) are arranged in a stereotypical pattern according to classes in the organs (sensilla) on the antennae. Those classes are further subdivided into subclasses. Those fall into zones and subzones. It's a highly organized arrangement, but it started from the same pool of precursor cells. How? The authors, primarily from Duke University, wanted to know. They began, "Developmental mechanisms spawning this extraordinary diversity of ORN classes from an initially homogenous population of precursors remain unknown." (Emphasis added.) So they investigated.

They found a transcription factor, Rotund (Rn), that "autonomously fine tunes the differentiation potential" of sensory organ precursors, "thereby regulating sensilla subtype specification by branching off novel precursor fates from default ones in each zone." The way Rn is expressed rapidly multiplies the possible outcomes, giving rise to distinct neuron classes that cluster together on specific sensilla subtypes. But Rn is only one of several transcription factors that act like ON/OFF switches. This led to a very elegant model:

In conjunction with the phenotypic analysis of previously identified factors that have early functions in ORN specification, we demonstrate a nested combinatorial strategy by which transcription factors are assembled together to progressively impose hierarchical and lineage-specific restrictions on ORN precursor differentiation potentials in order to generate ORN diversity. This nested organizational logic among a limited number of transcription factors provides an extremely efficient solution that potentially could be utilized in many other neural differentiation processes when high population diversity benefits survival.

In plain English, the fruit fly takes a small set of rules to generate an astonishing number of combinations. These rules (the transcription factors that decide what gene will be transcribed) are organized in nested hierarchies. As the embryo develops, the rules place the resulting neurons on the sensory organs in a stable arrangement according to classes and zones.

Our results suggest that nesting the regulatory relationship of transcription factor combinations allows the concurrent use of the same factors in parallel lineages to generate ORN diversity in a very efficient manner. Under this logic, binary lineage choices in precursor cells are made based on historical contingency, which could serve as an effective strategy for establishing cellular complexity in many other developing systems.

This is very cool. It's kind of like generating alphabetic letters, words and sentences from 1's and 0's in the ASCII computer coding scheme. With sequences of 8 bits (9 with parity bit included), you can generate a large variety of output, all from just two starting characters that act like "on" and "off" switches. Imagine the diversity of output you could generate with three or four switches. You could use combinations to define zones, classes, subzones, subclasses and other definitions to keep things orderly. In fruit flies and in humans, that's what happens. Combinatorial rules, based on binary logic, generate a huge diversity of specific receptors, all placed in a nested, organized way in the olfactory organs.

Of course, we oversimplify. You don't have to understand the following paragraph to realize a lot goes on in building a nose:

Our results along with others suggest a two-step mechanism for ORN diversification: (1) successive restrictions on precursor differentiation potentials by spatiotemporal factors, such as proneural/prepatterning gene products and Rn, and (2) segregation of restricted fates through Notch-mediated asymmetric divisions and local transcription factor networks for directly turning on olfactory receptor expression. Hypothetically, the sensilla precursor differentiation potentials can be represented by distinct sets of olfactory receptor genes being organized into euchromatic regions in a lineage-specific manner. The aforementioned combinations of transcription factors may influence the dynamics of such epigenetic states, resulting in limited combinations of receptors transcriptionally accessible for later stages of ORN differentiation....

There's a symphony of interrelated operations all working on the same score to produce an organized result. And that's just in a fruit fly. What happens when humans develop as a baby is beyond comprehension:

In comparison with the Drosophila olfactory system, mammals exhibit remarkable organizational similarities in the olfactory circuitry, even though the numerical complexity far exceeds that of their insect counterparts.

It's unexpected, though, that there would be so many similarities between fruit flies and humans in their olfactory developmental strategies, because we are not evolutionarily related to insects. Whatever "common ancestor" existed before Darwinists say the two diverged, it could not have had noses this complex. In another article in Current Biology, Elizabeth J. Hong and Rachel I. Wilson discuss additional similarities in the olfactory senses of zebrafish and fruit flies -- a means to "gain control" to ensure reliable response to odors despite huge variations in intensity. The organization of modules in their olfactory systems are also "remarkably similar," they say, between fish, fruit flies, and probably mammals.

Do the authors of the first paper really expect anyone to believe unrelated lineages developed similar systems independently? They do.

The model we present here also provides us with an ancestral precursor decision landscape that reveals the interaction pattern among factors to maintain and modify phenotypic complexity and diversity within sensory neural circuits on evolutionary timescales. New regulatory nodes might be added to the combinatorial code at distinct stages of precursor cell development to change ORN specification programs.... Incremental addition of individual regulatory modules to preexisting lineage-specific combinations operating in binary ON/OFF mode could facilitate the coordination of novel ORN fates with the evolution of receptor genes, which can be modified in response to changes in the quantity, quality, and context of the olfactory environment.

Well, anything "could" be true. It "might" happen. Hey, use your imagination, why don't you. But this is like saying that ASCII characters "could" develop into "novel" combinations, which "might" be added to preexisting words. These words "could" facilitate the coordination of novel sentences -- provided rules of grammar evolve at the same time. A little rain, sunshine or lightning "can" modify the sentences to fit the "quantity, quality, and context" of the reading "environment."

None of that would make any sense without a pre-existing commitment to the view that "We're here; therefore we evolved." But that is like saying "Books exist; therefore they emerged by aimless, unguided natural processes."

We've just seen words like specification, logic, code, regulation, circuitry, complexity, strategy, solution, and efficiency employed to describe the olfactory senses of animals. Those are intelligent design words. We have no experience with any natural phenomenon using those words (black holes, earthquakes, asteroid impacts), but we have a great deal of experience using those words to describe designed systems. The nose knows when it smells "design."

Image source: eren/Flickr.