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Large-scale trends in the evolution of gene structures within 11 animal genomes.

ABSTRACT: We have used the annotations of six animal genomes (Homo sapiens, Mus musculus, Ciona intestinalis, Drosophila melanogaster, Anopheles gambiae, and Caenorhabditis elegans) together with the sequences of five unannotated Drosophila genomes to survey changes in protein sequence and gene structure over a variety of timescales--from the less than 5 million years since the divergence of D. simulans and D. melanogaster to the more than 500 million years that have elapsed since the Cambrian explosion. To do so, we have developed a new open-source software library called CGL (for "Comparative Genomics Library"). Our results demonstrate that change in intron-exon structure is gradual, clock-like, and largely independent of coding-sequence evolution. This means that genome annotations can be used in new ways to inform, corroborate, and test conclusions drawn from comparative genomics analyses that are based upon protein and nucleotide sequence similarities.

SUBMITTER: Yandell M

PROVIDER: S-EPMC1386723 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Large-scale metagenome assemblies of human microbiomes have produced a vast catalogue of previously unseen microbial genomes; however, comparatively few microbial genomes derive from other vertebrates. Here, we generated 5,596 metagenome-assembled genomes (MAGs) from the gut metagenomes of 180 predominantly wild animal species representing 5 classes, in addition to 14 existing animal gut metagenome data sets. The MAGs comprised 1,522 species-level genome bins (SGBs), most of which were novel at the species, genus, or family level, and the majority were enriched in host versus environment metagenomes. Many traits distinguished SGBs enriched in host or environmental biomes, including the number of antimicrobial resistance genes. We identified 1,986 diverse biosynthetic gene clusters; only 23 clustered with any MIBiG database references. Gene-based assembly revealed tremendous gene diversity, much of it host or environment specific. Our MAG and gene data sets greatly expand the microbial genome repertoire and provide a broad view of microbial adaptations to the vertebrate gut.IMPORTANCE Microbiome studies on a select few mammalian species (e.g., humans, mice, and cattle) have revealed a great deal of novel genomic diversity in the gut microbiome. However, little is known of the microbial diversity in the gut of other vertebrates. We studied the gut microbiomes of a large set of mostly wild animal species consisting of mammals, birds, reptiles, amphibians, and fish. Unfortunately, we found that existing reference databases commonly used for metagenomic analyses failed to capture the microbiome diversity among vertebrates. To increase database representation, we applied advanced metagenome assembly methods to our animal gut data and to many public gut metagenome data sets that had not been used to obtain microbial genomes. Our resulting genome and gene cluster collections comprised a great deal of novel taxonomic and genomic diversity, which we extensively characterized. Our findings substantially expand what is known of microbial genomic diversity in the vertebrate gut.

Project description:ImportanceDespite favorable national trends in the incidence of end-stage renal disease (ESRD) from 2008 to 2011, ESRD incidence has been increasing recently, and less than 10% of patients with ESRD start renal replacement therapy with peritoneal dialysis (PD) in the United States. Given known and potential advantages of PD over hemodialysis, the Kaiser Permanente Northern California integrated health care delivery system implemented a program to expand use of PD.ObjectivesTo describe the system-level approach to expansion of PD use and temporal trends in initiation and persistence of PD and its associated mortality.Design, setting, and participantsThis retrospective cohort study included adult members of a large integrated health care delivery system in Northern California who initiated chronic dialysis therapy from January 1, 2008, through December 31, 2018. Data were analyzed from March 1, 2018, through May 31, 2019.ExposureFrom 2008 to 2018, Kaiser Permanente Northern California implemented a multidisciplinary, system-wide approach to increase use of PD that included patient and caregiver education, education and support tools for health care professionals, streamlined system-level processes, monitoring, and continuous quality improvement.Main outcomes and measuresTemporal trends in the proportion of patients starting chronic dialysis with PD vs hemodialysis compared with national trends. Secondary outcomes included persistence of PD at 1 year in those initiating it and standardized 1-year mortality rates in those initiating PD or hemodialysis.ResultsAmong 13 500 eligible health plan members in the study population (7840 men [58.1%] and 5660 women [41.9%]; mean [SD] age, 64.3 [14.4] years), initiation of PD increased from 165 of 1089 all new dialysis patients (15.2%) in 2008 to 486 of 1438 (33.8%) in 2018, which was substantially higher than national trends (6.1% in 2008 and 9.7% in 2016). Among the 2974 patients who initiated PD from 2008 to 2017, 2387 (80.3%) continued PD at 1 year after initiation, with a significant increase in age-, sex-, and race-standardized rates from 2008 (69.1%) to 2017 (84.2%). Age-, sex-, and race-standardized 1-year mortality for patients receiving PD and hemodialysis did not change significantly across this 10-year period (17.3% to 15.5% for hemodialysis, P = 0.89 for trend; and 5.5% to 7.3% for PD, P = 0.12 for trend).Conclusions and relevanceThis study suggests that large-scale expansion of PD is feasible using a multidisciplinary, integrated, coordinated care approach; we believe these findings represent a national opportunity to improve outcomes for patients with advanced kidney disease.

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Large-scale trends in the evolution of gene structures within 11 animal genomes.

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