Evidence for a strong correlation between transcription factor protein disorder and organismic complexity

Studies of diverse phylogenetic lineages reveal that protein disorder increases in concert with organismic complexity but that differences nevertheless exist among lineages. To gain insight into this phenomenology, we analyzed all of the transcription factor (TF) families for which sequences are known for 17 species spanning bacteria, yeast, algae, land plants, and animals and for which the number of different cell types has been reported in the primary literature. Although the fraction of disordered residues in TF sequences is often moderately or poorly correlated with organismic complexity as gauged by cell-type number (r20.8). Furthermore, the correlation between the fraction of disordered residues and cell-type number becomes stronger when confined to the TF families participating in cell cycle, cell size, cell division, cell differentiation, or cell proliferation, and other important developmental processes. The data also indicate that evolutionarily simpler organisms allow for the detection of subtle differences in the conserved IDRs of TFs as well as changes in variable IDRs, which can influence the DNA recognition and multifunctionality of TFs through direct or indirect mechanisms. Although strong correlations cannot be taken as evidence for causeand-effect relationships, we interpret our data to indicate that increasing TF disorder likely was an important factor contributing to the evolution of organismic complexity and not merely a concurrent unrelated effect of increasing organismic complexity

Evolution of Protein Ductility in Duplicated Genes of Plants

Previous work has shown that ductile/intrinsically disordered proteins (IDPs) and residues (IDRs) are found in all unicellular and multicellular organisms, wherein they are essential for basic cellular functions and complement the function of rigid proteins. In addition, computational studies of diverse phylogenetic lineages have revealed: (1) that protein ductility increases in concert with organismic complexity, and (2) that distributions of IDPs and IDRs along the chromosomes of plant species are non-random and correlate with variations in the rates of the genetic recombination and chromosomal rearrangement. Here, we show that approximately 50% of aligned residues in paralogs across a spectrum of algae, bryophytes, monocots, and eudicots are IDRs and that a high proportion (ca. 60%) are in disordered segments greater than 30 residues. When three types of IDRs are distinguished (i.e., identical, similar and variable IDRs) we find that species with large numbers of chromosome and endoduplicated genes exhibit paralogous sequences with a higher frequency of identical IDRs, whereas species with small chromosomes numbers exhibit paralogous sequences with a higher frequency of similar and variable IDRs. These results are interpreted to indicate that genome duplication events influence the distribution of IDRs along protein sequences and likely favor the presence of identical IDRs (compared to similar IDRs or variable IDRs). We discuss the evolutionary implications of gene duplication events in the context of ductile/disordered residues and segments, their conservation, and their effects on functionality

Evaluation of national surgical practice for lateral lymph nodes in rectal cancer in an untrained setting

Background. Involved lateral lymph nodes (LLNs) have been associated with increased local recurrence (LR) and ipsi-lateral LR (LLR) rates. However, consensus regarding the indication and type of surgical treatment for suspicious LLNs is lacking. This study evaluated the surgical treatment of LLNs in an untrained setting at a national level.Methods. Patients who underwent additional LLN surgery were selected from a national cross-sectional cohort study regarding patients undergoing rectal cancer surgery in 69 Dutch hospitals in 2016. LLN surgery consisted of either 'node-picking' (the removal of an individual LLN) or 'partial regional node dissection' (PRND; an incomplete resection of the LLN area). For all patients with primarily enlarged (=7 mm) LLNs, those undergoing rectal surgery with an additional LLN procedure were compared to those undergoing only rectal resection.Results. Out of 3057 patients, 64 underwent additional LLN surgery, with 4-year LR and LLR rates of 26% and 15%, respectively. Forty-eight patients (75%) had enlarged LLNs, with corresponding recurrence rates of 26% and 19%, respectively. Node-picking (n = 40) resulted in a 20% 4-year LLR, and a 14% LLR after PRND (n = 8; p = 0.677). Multivariable analysis of 158 patients with enlarged LLNs undergoing additional LLN surgery (n = 48) or rectal resection alone (n = 110) showed no significant association of LLN surgery with 4-year LR or LLR, but suggested higher recurrence risks after LLN surgery (LR: hazard ratio [HR] 1.5, 95% confidence interval [CI] 0.7-3.2, p = 0.264; LLR: HR 1.9, 95% CI 0.2-2.5, p = 0.874).Conclusion. Evaluation of Dutch practice in 2016 revealed that approximately one-third of patients with primarily enlarged LLNs underwent surgical treatment, mostly consisting of node-picking. Recurrence rates were not significantly affected by LLN surgery, but did suggest worse outcomes. Outcomes of LLN surgery after adequate training requires further research