or•gan•ic | ôr’ganik | adjective. denoting a relation between elements of something such that they fit together harmoniously as necessary parts of a whole; characterized by continuous or natural development.
One of the wonderful things about how development works is that organisms function as wholes, and changes in one property trivially induce concordant changes in other properties. Tug on one element, changing it’s orientation or size, and during embryogenesis any adjacent elements make compensatory adjustments, so that the resultant form flows, fits, and looks organic. This isn’t that surprising a feature of development, though, unless you have the mistaken idea that the genome encodes a blueprint of morphology. It doesn’t; what it contains is a description of interacting agents that work together in a process to produce a complex result. Changes in genes and regulatory elements can essentially produce changes in rules of development, rather than crudely specifying blocks of morphology.
What does this mean for evolution? It means that subtle changes to the rules of development can be caused by small changes to genes (and especially, to regulatory regions of genes), and that the resulting morphological changes may be dramatic, but are still integrated organically into the form of the organism as a whole. Our understanding of how development works is making it clear that large scale macroevolutionary change may be much easier than we had thought.
Here’s an example where this insight is clarifying the evolution of an organism: the fossil record of bats shows an abrupt appearance of fairly sophisticated creatures with elongated digits, clearly capable of gliding or powered flight, with no known intermediates. We expect there were less fully flight-ready predecessors, but fossil preservation is not kind to small, delicate boned animals. It’s also possible that the transitional period was fairly brief; it looks like turning a paw into a long-fingered membranous wing may be a fairly simple change on a molecular level.
This is a story about how short, stubby finger bones are turned into long, thin finger bones, so let’s start with how the bones of the hand form. Like all the long bones of the body, it begins with a condensation of mesenchymal tissue (this just tissue where the cells are connected in a loose network, swimming in a soup of extracellular proteins, and are relatively free to move) to form knots of cartilaginous cells where each digit will form. These cells proliferate and organize themselves into rods of a rubbery extracellular matrix. Continued growth is by continued proliferation of these cells, which extends the length of the rod. Later, other cells invade the cartilaginous matrix and replace the more flexible early cartilage with bone. When the digit is completely ossified, growth stops (we keep bones growing for a long time by setting aside specific regions, growth plates, that retain their proliferative cartilaginous nature.)
The proliferation of the early cells is a key control point. Keep them dividing longer before replacing them with bone, and the digit grows longer. Start the ossification process earlier, and you end up with short digits by truncating the proliferation process. How is that period of growth regulated?
There is a whole family of proteins called the BMPs—Bone morphogenetic proteins—that modulate bone growth, as you might expect from the name. In particular, one member of the family, Bmp2 is expressed specifically in hypertrophic cells of the growth plate in mice. As it turns out, if you take an embryonic mouse limb and culture it in a dish soaked with Bmp2, the digits grow longer; put an embryonic mouse limb in a dish that contains the protein Noggin, which antagonizes the function of Bmp, and the digits are stunted. This is suggestive: Bmp2 concentration could be the vernier that regulates digit length. Add more, fingers grow long, and add less, they grow short and stubby.
That work is all done in mice…so what about bats? There has been some fascinating work on bat embryology lately, and here’s one relevant result: in the early bat embryo, the proportions of the limbs and digits are indistinguishable from the proportions of the mouse. That means the organization of the tissue is initially similar, and only later, as the bones of the limb develop in that process regulated by the Bmps, do the proportions change.
These embryonic bat limbs can be snipped off and grown in culture as well, in the presence of either Bmp2 or Noggin. To no one’s surprise, the digits grow longer in Bmp2, shorter in Noggin.
But there’s more! Bats have elongated digits in their forelimbs, but not in their hindlimbs. Quantitative analysis of the distribution of the Bmp proteins in the limbs shows that levels of Bmp2 in the hindlimb was roughly equivalent to what’s found in the mouse, but that Bmp2 levels were about 35% higher in the bat forelimb than either in mouse limbs or the bat hindlimb. Other members of the Bmp family do not show any correlated differences.
What this means is that the authors have identified a discrete molecule with a difference in its expression in the bat, and that this molecule is specifically involved in regulating digit length. This is a significant step in figuring out the evolutionary pathway that led to the bat wing.
Together, our results indicate the up-regulation of the Bmp
pathway as a major and fundamental (although not necessarily
the only) mechanism responsible for the developmental elongation of bat forelimb digits. Based on our results, we raise the
intriguing possibilit y that a similar up-regulation of the Bmp
pathway had a role in the evolutionary elongation of bat forelimb
digits, which is an event that was critical to the achievement of
powered flight in bats. Recent studies have suggested
that modifications to the cis-regulator y elements of developmental genes have central roles in the evolutionary diversifica-
tion of morphology. Our evidence that Bmp2, but not Bmp4 or
Bmp7, is differentially expressed in the bat wing digits is suggestive of a cis-regulatory change that affects the level, but not
the temporal or spatial regulation, of Bmp2 expression. By
linking a simple change in a single developmental pathway to
dramatically different morphologies, we provide a potential
explanation as to how bats were able to achieve powered flight
soon after they diverged from other mammals nearly 65 million
Like the authors say, it’s not likely to be the only step involved. I would imagine that mutations in the Bmp2 pathway would have led to long-fingered ancestral Chiropteran, and another change might have suppressed apoptosis in the finger webbing to produce a large flat membranous wing-hand; this might have been a the first step in producing an animal capable of simple gliding. Coordinated, powered flight would have required a suite of genetic changes…but that first step that would have launched an animal in the direction of flight could have been very easy to achieve.
Sears KE, Behringer RR, Rasweiler JJ, Niswander LA (2006) Development of bat flight: Morphologic and molecular evolution of bat wing digits. Proc. Nat. Acad. Sci. USA 103(17):6581-6586.
The SciAm blog also has a summary.