Cis-by-Trans Regulatory Divergence Causes the Asymmetric Lethal Effects of an Ancestral Hybrid Incompatibility Gene

The Dobzhansky and Muller (D-M) model explains the evolution of hybrid incompatibility (HI) through the interaction between lineage-specific derived alleles at two or more loci. In agreement with the expectation that HI results from functional divergence, many protein-coding genes that contribute to incompatibilities between species show signatures of adaptive evolution, including Lhr, which encodes a heterochromatin protein whose amino acid sequence has diverged extensively between Drosophila melanogaster and D. simulans by natural selection. The lethality of D. melanogaster/D. simulans F1 hybrid sons is rescued by removing D. simulans Lhr, but not D. melanogaster Lhr, suggesting that the lethal effect results from adaptive evolution in the D. simulans lineage. It has been proposed that adaptive protein divergence in Lhr reflects antagonistic coevolution with species-specific heterochromatin sequences and that defects in LHR protein localization cause hybrid lethality. Here we present surprising results that are inconsistent with this coding-sequence-based model. Using Lhr transgenes expressed under native conditions, we find no evidence that LHR localization differs between D. melanogaster and D. simulans, nor do we find evidence that it mislocalizes in their interspecific hybrids. Rather, we demonstrate that Lhr orthologs are differentially expressed in the hybrid background, with the levels of D. simulans Lhr double that of D. melanogaster Lhr. We further show that this asymmetric expression is caused by cis-by-trans regulatory divergence of Lhr. Therefore, the non-equivalent hybrid lethal effects of Lhr orthologs can be explained by asymmetric expression of a molecular function that is shared by both orthologs and thus was presumably inherited from the ancestral allele of Lhr. We present a model whereby hybrid lethality occurs by the interaction between evolutionarily ancestral and derived alleles

Sequence extension of RAPD markers to increase their utility for hybrid purity testing

WOS: 000222515700020Analysis of Random Amplified Polymorphic DNA (RAPD) was evaluated as a tool for testing hybrid purity in tomato varieties. Four F, tomato hybrids (L. esculentum Mill.) and their parents were analyzed with eight 10-mer primers. Out of the primers tested, five primers generated useful RAPD markers to determine the hybrid seed purity of three varieties. Also, various combinations of a primer (AF14) were tested by sequence extension of its termini in order to increase the utility of this primer. These combinations presented additional RAPD markers to test hybrid purity of more than one hybrid variety. Primer AF14 gave one useful marker for identifying hybrid purity of one variety. Therefore, the use of a primer sequence extended at its termini can be suggested to test hybrid purity more efficiently

Macroeconomic costs of the unmet burden of surgical disease in Sierra Leone: A retrospective economic analysis

Objective The Lancet Commission on Global Surgery estimated that low/middle-income countries will lose an estimated cumulative loss of 12.3 trillion US Dollars from gross domestic product (GDP) due to the unmet burden of surgical disease. However, no country-specific data currently exist. We aimed to estimate the costs to the Sierra Leone economy from death and disability which may have been averted by surgical care. Design We used estimates of total, met and unmet need from two main sources—a cluster randomised, cross-sectional, countrywide survey and a retrospective, nationwide study on surgery in Sierra Leone. We calculated estimated disability-adjusted life years from morbidity and mortality for the estimated unmet burden and modelled the likely economic impact using three different methods—gross national income per capita, lifetime earnings foregone and value of a statistical life. Results In 2012, estimated, discounted lifetime losses to the Sierra Leone economy from the unmet burden of surgical disease was between 1.1 and 3.8 billion US Dollars, depending on the economic method used. These lifetime losses equate to between 23% and 100% of the annual GDP for Sierra Leone. 80% of economic losses were due to mortality. The incremental losses averted by scale up of surgical provision to the Lancet Commission target of 80% were calculated to be between 360 million and 2.9 billion US Dollars. Conclusion There is a large economic loss from the unmet need for surgical care in Sierra Leone. There is an immediate need for massive investment to counteract ongoing economic losses.</p

Macroeconomic costs of the unmet burden of surgical disease in Sierra Leone: A retrospective economic analysis

Objective The Lancet Commission on Global Surgery estimated that low/middle-income countries will lose an estimated cumulative loss of 12.3 trillion US Dollars from gross domestic product (GDP) due to the unmet burden of surgical disease. However, no country-specific data currently exist. We aimed to estimate the costs to the Sierra Leone economy from death and disability which may have been averted by surgical care. Design We used estimates of total, met and unmet need from two main sources—a cluster randomised, cross-sectional, countrywide survey and a retrospective, nationwide study on surgery in Sierra Leone. We calculated estimated disability-adjusted life years from morbidity and mortality for the estimated unmet burden and modelled the likely economic impact using three different methods—gross national income per capita, lifetime earnings foregone and value of a statistical life. Results In 2012, estimated, discounted lifetime losses to the Sierra Leone economy from the unmet burden of surgical disease was between 1.1 and 3.8 billion US Dollars, depending on the economic method used. These lifetime losses equate to between 23% and 100% of the annual GDP for Sierra Leone. 80% of economic losses were due to mortality. The incremental losses averted by scale up of surgical provision to the Lancet Commission target of 80% were calculated to be between 360 million and 2.9 billion US Dollars. Conclusion There is a large economic loss from the unmet need for surgical care in Sierra Leone. There is an immediate need for massive investment to counteract ongoing economic losses.</p