ASU Regents' Professors Open Access Works
The title “Regents’ Professor” is the highest faculty honor awarded at Arizona State University. It is conferred on ASU faculty who have made pioneering contributions in their areas of expertise, who have achieved a sustained level of distinction, and who enjoy national and international recognition for these accomplishments. This collection contains primarily open access works by ASU Regents' Professors.
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- Creators: School of Geographical Sciences and Urban Planning
- Creators: BEYOND: Center for Fundamental Concepts in Science
Cancer is sometimes depicted as a reversion to single cell behavior in cells adapted to live in a multicellular assembly. If this is the case, one would expect that mutation in cancer disrupts functional mechanisms that suppress cell-level traits detrimental to multicellularity. Such mechanisms should have evolved with or after the emergence of multicellularity. This leads to two related, but distinct hypotheses: 1) Somatic mutations in cancer will occur in genes that are younger than the emergence of multicellularity (1000 million years [MY]); and 2) genes that are frequently mutated in cancer and whose mutations are functionally important for the emergence of the cancer phenotype evolved within the past 1000 million years, and thus would exhibit an age distribution that is skewed to younger genes. In order to investigate these hypotheses we estimated the evolutionary ages of all human genes and then studied the probability of mutation and their biological function in relation to their age and genomic location for both normal germline and cancer contexts.
We observed that under a model of uniform random mutation across the genome, controlled for gene size, genes less than 500 MY were more frequently mutated in both cases. Paradoxically, causal genes, defined in the COSMIC Cancer Gene Census, were depleted in this age group. When we used functional enrichment analysis to explain this unexpected result we discovered that COSMIC genes with recessive disease phenotypes were enriched for DNA repair and cell cycle control. The non-mutated genes in these pathways are orthologous to those underlying stress-induced mutation in bacteria, which results in the clustering of single nucleotide variations. COSMIC genes were less common in regions where the probability of observing mutational clusters is high, although they are approximately 2-fold more likely to harbor mutational clusters compared to other human genes. Our results suggest this ancient mutational response to stress that evolved among prokaryotes was co-opted to maintain diversity in the germline and immune system, while the original phenotype is restored in cancer. Reversion to a stress-induced mutational response is a hallmark of cancer that allows for effectively searching “protected” genome space where genes causally implicated in cancer are located and underlies the high adaptive potential and concomitant therapeutic resistance that is characteristic of cancer.
Aim
To establish a chronology for late Quaternary avian extinction, extirpation and persistence in the Bahamas, thereby testing the relative roles of climate change and human impact as causes of extinction.
Location
Great Abaco Island (Abaco), Bahamas, West Indies.
Methods
We analysed the resident bird community as sampled by Pleistocene (> 11.7 ka) and Holocene (< 11.7 ka) fossils. Each species was classified as extinct (lost globally), extirpated (gone from Abaco but persists elsewhere), or extant (still resident on Abaco). We compared patterns of extinction, extirpation and persistence to independent estimates of climate and sea level for glacial (late Pleistocene) and interglacial (Holocene) times.
Results
Of 45 bird species identified in Pleistocene fossils, 25 (56%) no longer occur on Abaco (21 extirpated, 4 extinct). Of 37 species recorded in Holocene deposits, 15 (14 extirpated, 1 extinct; total 41%) no longer exist on Abaco. Of the 30 extant species, 12 were recovered as both Pleistocene and Holocene fossils, as were 9 of the 30 extirpated or extinct species. Most of the extinct or extirpated species that were only recorded from Pleistocene contexts are characteristic of open habitats (pine woodlands or grasslands); several of the extirpated species are currently found only where winters are cooler than in the modern or Pleistocene Bahamas. In contrast, most of the extinct or extirpated species recorded from Holocene contexts are habitat generalists.
Main conclusions
The fossil evidence suggests two main times of late Quaternary avian extirpation and extinction in the Bahamas. The first was during the Pleistocene–Holocene transition (PHT; 15–9 ka) and was fuelled by climate change and associated changes in sea level and island area. The second took place during the late Holocene (< 4 ka, perhaps primarily < 1 ka) and can be attributed to human impact. Although some species lost during the PHT are currently found where climates are cooler and drier than in the Bahamas today, a taxonomically and ecologically diverse set of species persisted through that major climate change but did not survive the past millennium of human presence.