Search for: All records

This investigation reveals quantitative patterns governing proteotype diversity and coevolution in mammalian cells. 

Abstract CD44 is an extracellular matrix receptor implicated in cancer progression. CD44 increases the invasibility of skin (SF) and endometrial stromal fibroblasts (ESF) by cancer and trophoblast cells. We reasoned that the evolution of CD44 expression can affect both, the fetal–maternal interaction through CD44 in ESF as well as vulnerability to malignant cancer through expression in SF. We studied the evolution of CD44 expression in mammalian SF and ESF and demonstrate that in the human lineage evolved higher CD44 expression. Isoform expression in cattle and human is very similar suggesting that differences in invasibility are not due to the nature of expressed isoforms. We then asked whether the concerted gene expression increase in both cell types is due to shared regulatory mechanisms or due to cell type-specific factors. Reporter gene experiments with cells and cis-regulatory elements from human and cattle show that the difference of CD44 expression is due to cis effects as well as cell type-specific trans effects. These results suggest that the concerted expression increase is likely due to selection acting on both cell types because the evolutionary change in cell type-specific factors requires selection on cell type-specific functions. This scenario implies that the malignancy enhancing effects of elevated CD44 expression in humans likely evolved as a side-effect of positive selection on a yet unidentified other function of CD44. A possible candidate is the anti-fibrotic effect of CD44 but there are no reliable data showing that humans and primates are less fibrotic than other mammals. 

Abstract Reduced limbs and limblessness have evolved independently in many lizard clades. Scincidae exhibit a wide range of limb‐reduced morphologies, but only some species have been used to study the embryology of limb reduction (e.g., digit reduction inChalcidesand limb reduction inScelotes). The genusBrachymeles, a Southeast Asian clade of skinks, includes species with a range of limb morphologies, from pentadactyl to functionally and structurally limbless species. Adults of the small, snake‐like speciesBrachymeles lukbanishow no sign of external limbs in the adult except for small depressions where they might be expected to occur. Here, we show that embryos ofB. lukbaniin early stages of development, on the other hand, show a truncated but well‐developed limb with a stylopod and a zeugopod, but no signs of an autopod. As development proceeds, the limb's small size persists even while the embryo elongates. These observations are made based on external morphology. We used florescent whole‐mount immunofluorescence to visualize the morphology of skeletal elements and muscles within the embryonic limb ofB. lukabni. Early stages have a humerus and separated ulna and radius cartilages; associated with these structures are dorsal and ventral muscle masses as those found in the embryos of other limbed species. While the limb remains small, the pectoral girdle grows in proportion to the rest of the body, with well‐developed skeletal elements and their associated muscles. In later stages of development, we find the small limb is still present under the skin, but there are few indications of its presence, save for the morphology of the scale covering it. By use of CT scanning, we find that the adult morphology consists of a well‐developed pectoral girdle, small humerus, extremely reduced ulna and radius, and well‐developed limb musculature connected to the pectoral girdle. These muscles form in association with a developing limb during embryonic stages, a hint that “limbless” lizards that possess these muscles may have or have had at least transient developing limbs, as we find inB. lukbani. Overall, this newly observed pattern of ontogenetic reduction leads to an externally limbless adult in which a limb rudiment is hidden and covered under the trunk skin, a situation calledcryptomelia. The results of this work add to our growing understanding of clade‐specific patterns of limb reduction and the convergent evolution of limbless phenotypes through different developmental processes.