On the Growth of Scientific Knowledge: Yeast Biology as a Case Study

The tempo and mode of human knowledge expansion is an enduring yet poorly understood topic. Through a temporal network analysis of three decades of discoveries of protein interactions and genetic interactions in baker's yeast, we show that the growth of scientific knowledge is exponential over time and that important subjects tend to be studied earlier. However, expansions of different domains of knowledge are highly heterogeneous and episodic such that the temporal turnover of knowledge hubs is much greater than expected by chance. Familiar subjects are preferentially studied over new subjects, leading to a reduced pace of innovation. While research is increasingly done in teams, the number of discoveries per researcher is greater in smaller teams. These findings reveal collective human behaviors in scientific research and help design better strategies in future knowledge exploration

Unique Signatures of Natural Background Radiation on Human Y Chromosomes from Kerala, India

The most frequently observed major consequences of ionizing radiation are chromosomal lesions and cancers, although the entire genome may be affected. Owing to its haploid status and absence of recombination, the human Y chromosome is an ideal candidate to be assessed for possible genetic alterations induced by ionizing radiation. We studied the human Y chromosome in 390 males from the South Indian state of Kerala, where the level of natural background radiation (NBR) is ten-fold higher than the worldwide average, and that from 790 unexposed males as control.We observed random microdeletions in the Azoospermia factor (AZF) a, b and c regions in >90%, and tandem duplication and copy number polymorphism (CNP) of 11 different Y-linked genes in about 80% of males exposed to NBR. The autosomal homologues of Y-linked CDY genes largely remained unaffected. Multiple polymorphic copies of the Y-linked genes showing single Y-specific signals suggested their tandem duplication. Some exposed males showed unilocus duplication of DAZ genes resulting in six copies. Notably, in the AZFa region, approximately 25% of exposed males showed deletion of the DBY gene, whereas flanking genes USP9Y and UTY remained unaffected. All these alterations were detected in blood samples but not in the germline (sperm) samples.Exposure to high levels of NBR correlated with several interstitial polymorphisms of the human Y chromosome. CNPs and enhanced transcription of the SRY gene after duplication are envisaged to compensate for the loss of Y chromosome in some cells. The aforesaid changes, confined to peripheral blood lymphocytes, suggest a possible innate mechanism protecting the germline DNA from the NBR. Genome analysis of a larger population focusing on greater numbers of genes may provide new insights into the mechanisms and risks of the resultant genetic damages. The present work demonstrates unique signatures of NBR on human Y chromosomes from Kerala, India

Genetic Incompatibility Dampens Hybrid Fertility More Than Hybrid Viability: Yeast as a Case Study

Genetic incompatibility is believed to be the major cause of postzygotic reproductive isolation. Despite huge efforts seeking for speciation-related incompatibilities in the past several decades, a general understanding of how genetic incompatibility evolves in affecting hybrid fitness is not available, primarily due to the fact that the number of known incompatibilities is small. Instead of further mapping specific incompatible genes, in this paper we aimed to know the overall effects of incompatibility on fertility and viability, the two aspects of fitness, by examining 89 gametes produced by yeast S. cerevisiae - S. paradoxus F1 hybrids. Homozygous F2 hybrids formed by autodiploidization of F1 gametes were subject to tests for growth rate and sporulation efficiency. We observed much stronger defects in sporulation than in clonal growth for every single F2 hybrid strain, indicating that genetic incompatibility affects hybrid fertility more than hybrid viability in yeast. We related this finding in part to the fast-evolving nature of meiosis-related genes, and proposed that the generally low expression levels of these genes might be a cause of the observation

Reduced intrinsic DNA curvature leads to increased mutation rate

Background: Mutation rates vary across the genome. Many trans factors that influence mutation rates have been identified, as have specific sequence motifs at the 1–7-bp scale, but cis elements remain poorly characterized. The lack of understanding regarding why different sequences have different mutation rates hampers our ability to identify positive selection in evolution and to identify driver mutations in tumorigenesis. Results: Here, we use a combination of synthetic genes and sequences of thousands of isolated yeast colonies to show that intrinsic DNA curvature is a major cis determinant of mutation rate. Mutation rate negatively correlates with DNA curvature within genes, and a 10% decrease in curvature results in a 70% increase in mutation rate. Consistently, both yeast and humans accumulate mutations in regions with small curvature. We further show that this effect is due to differences in the intrinsic mutation rate, likely due to differences in mutagen sensitivity and not due to differences in the local activity of DNA repair. Conclusions: Our study establishes a framework for understanding the cis properties of DNA sequence in modulating the local mutation rate and identifies a novel causal source of non-uniform mutation rates across the genome