 Evolution of the lacrimal gland. This is the lacrimal gland. Either spelling is correct. It produces tears. Tears protect the eyes from scratches and infections. They moisten and coat the eye. They can also show emotion like disappointment in the white man's carelessness. If you were born after 1978, you may need to ask your parents about this reference. There are three types of tears. Basil, reflex, and emotional. Basil tears are composed by weight of 96% water, 3.5% salts, and 0.5% other. It's the 0.5% other that I want to focus on. That 0.5% is mucin, glycerophospholipids, lysozyme, lactoferrin, lipokalin, lacritin, immunoglobulins, and glucose. Are any of these unique to tear fluid? No. As it turns out, all those components are present in other fluids. Mucin, for example, is present in all mucous, all mucous membranes. Glyso, glycerophospholipids are also in all mucous, lysozyme is found in saliva and mucous, lactoferrin is found in milk saliva and mucous, lipokalin is found in saliva and mucous, even in the nerve sheath, lacritin is found in saliva, immunoglobulins are found throughout the body, and of course glucose is found in every cell in the body. So, tears are very similar to saliva and mucous. So, there's nothing unique being produced by the lacrimal gland. It's also structurally very similar to other exocrine glands, like the pancreas, salivary, mammary glands. So, here's the lacrimal gland compared to the pancreas and the gallbladder. So, what gene controls the development of this specialized exocrine gland that produces watery mucous? In humans, it's OTX-1, short for orthodontical homeobox-1. If evolution is true, we would predict a pattern of homology to other mammals. As it turns out, all mammals have 97% protein homology to the human OTX-1 gene product, despite DNA sequences showing increasing differences with evolutionary distance. Even fish, and as I will show flies have OTX-1. Drosophila has a homeobox gene that is homologous to OTX-1 called OTD, short for orthodontical. It controls many aspects of eye development, but how similar is it? How about if we cut the gene out of flies and paste it into mice in place of OTX-1? Here's the wild-type mouse lacrimal gland, it's marked LG, but if we knock out the OTX-1 gene, no more lacrimal gland. This is called an OTX-1 minus mutant or knockout. What if we substitute in the drosophila fly OTD gene? Hey, we get the lacrimal glands back. So, a fly gene for eye development is functional to make tear glands in a mouse. Flies don't even have tear ducts. How could the fly gene do this? Because OTX is the product of evolution. It evolved from a gene in the common ancestor of flies and mice. It turns out mice have CRX, OTX-1, and OTX-2. CRX is a cone rod homeobox. OTX-1 and OTX-2 are involved in brain and eye development. Can we infer any kind of relationship between CTX, OTX-1, and OTX-2? How similar are they? Very similar. These three genes are clearly related to each other. And they all three share a strong homology to the fly OTD gene. So, here's a plausible explanation for the evolution of the lacrimal gland. Step 1, a homeobox gene for an Xocrine gland in bilaterians duplicates and diverges over time, producing an OT-like gene. The OTD-like transcription factor becomes associated with eye and brain development. Later duplication and divergence result in specialized homeobox genes for different processes in development. One of these is OTX-1 invertebrates. The Xocrine-related genes are currently being driven by another bicoid transcription factor. This bicoid transcription factor is specific to, I don't know, pancreas, gastric, or salivary glands specific homeoboxes. I'm guessing salivary, which is Hox B13 because of the similarities in expressed proteins. The bicoid transcription factor, binding site, mutates to be preferentially bound by OTX-1, producing a new Xocrine gland attached to the eye. It secretes a saliva-like coating over the eye, protecting it and increasing fitness in the organism. Over time, more genes join the OTX-1 enhanced cluster, producing modern lacrimal glands. Thank you and please, don't litter.