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Natural selection shaped regional mtDNA variation in humans.

ABSTRACT: Human mtDNA shows striking regional variation, traditionally attributed to genetic drift. However, it is not easy to account for the fact that only two mtDNA lineages (M and N) left Africa to colonize Eurasia and that lineages A, C, D, and G show a 5-fold enrichment from central Asia to Siberia. As an alternative to drift, natural selection might have enriched for certain mtDNA lineages as people migrated north into colder climates. To test this hypothesis we analyzed 104 complete mtDNA sequences from all global regions and lineages. African mtDNA variation did not significantly deviate from the standard neutral model, but European, Asian, and Siberian plus Native American variations did. Analysis of amino acid substitution mutations (nonsynonymous, Ka) versus neutral mutations (synonymous, Ks) (kaks) for all 13 mtDNA protein-coding genes revealed that the ATP6 gene had the highest amino acid sequence variation of any human mtDNA gene, even though ATP6 is one of the more conserved mtDNA proteins. Comparison of the kaks ratios for each mtDNA gene from the tropical, temperate, and arctic zones revealed that ATP6 was highly variable in the mtDNAs from the arctic zone, cytochrome b was particularly variable in the temperate zone, and cytochrome oxidase I was notably more variable in the tropics. Moreover, multiple amino acid changes found in ATP6, cytochrome b, and cytochrome oxidase I appeared to be functionally significant. From these analyses we conclude that selection may have played a role in shaping human regional mtDNA variation and that one of the selective influences was climate.

SUBMITTER: Mishmar D

PROVIDER: S-EPMC140917 | biostudies-literature | 2003 Jan

REPOSITORIES: biostudies-literature

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Natural selection shaped regional mtDNA variation in humans.

Mishmar Dan D Ruiz-Pesini Eduardo E Golik Pawel P Macaulay Vincent V Clark Andrew G AG Hosseini Seyed S Brandon Martin M Easley Kirk K Chen Estella E Brown Michael D MD Sukernik Rem I RI Olckers Antonel A Wallace Douglas C DC

Proceedings of the National Academy of Sciences of the United States of America 20021230 1

Human mtDNA shows striking regional variation, traditionally attributed to genetic drift. However, it is not easy to account for the fact that only two mtDNA lineages (M and N) left Africa to colonize Eurasia and that lineages A, C, D, and G show a 5-fold enrichment from central Asia to Siberia. As an alternative to drift, natural selection might have enriched for certain mtDNA lineages as people migrated north into colder climates. To test this hypothesis we analyzed 104 complete mtDNA sequence ...[more]

PMID: 12509511

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Project description:Significant regional variation in surgical rates has been identified following multiple surgical procedures. However, limited data have examined the regional variability in patient selection and treatment of abdominal aortic aneurysms (AAAs). This study aimed to evaluate regional variation in patient selection, perioperative management, and operative approach for the repair of AAAs.All patients undergoing open repair or endovascular aneurysm repair (EVAR) of an AAA in the Vascular Quality Initiative from 2009 to 2014 were identified. All regional groups were deidentified, and those with fewer than 100 open repairs were combined into a single region.We identified 17,269 elective repairs (EVAR, 13,759; open, 3510) and 1462 ruptured AAAs (EVAR, 749; open, 713). There was significant regional variation in the use of EVAR for elective repair (range, 66%-88%; P < .01) and ruptured AAA repair (40%-80%; P < .01). The median diameter for elective repair was similar among regions (EVAR, 5.4 cm; open, 5.7 cm). There was wide variation in the treatment of small aneurysms in male patients (<5.5 cm) for EVAR (34%-49%; P < .01) and open repair (17%-38%; P < .01) and variation in the treatment of small aneurysms in female patients (<5 cm) for EVAR (14%-32%; P < .01) but not significant for open repair (6%-24%). For elective cases, preoperative aspirin (EVAR, 50%-75% [P < .01]; open, 49%-78% [P < .01]) and statin use (EVAR, 61%-75% [P < .01]; open, 56%-80% [P < .01]) varied widely. Among elective cardiac patients, preoperative management varied significantly, including beta-blocker use (EVAR, 66%-78% [P < .01]; open, 69%-88% [P = .01]) and the frequency of stress tests (EVAR, 33%-64% [P < .01]; open, 31%-73% [P < .01]). Among open repairs for aneurysms extending at or beyond the juxtarenal segment, there was wide variation in the use of retroperitoneal exposures (7%-70%; P < .01) and adjunctive renal protective measures (cold renal perfusion, 2%-43% [P < .01]; mannitol, 47%-92% [P < .01]).Significant regional variation exists in patient selection, perioperative management, and operative approach for the repair of AAA. Definitive evidence is lacking in many aspects of operative care, including the use of the retroperitoneal approach and renal protective strategies. However, this variation emphasizes the importance of research to determine best practice in the areas of greatest variation. Furthermore, where current clinical process measures exist and data are clear, such as the use of statin and antiplatelet agents, the high degree of variation should serve as an impetus for regional quality improvement projects.

Dataset Information

Natural selection shaped regional mtDNA variation in humans.

Publications

Natural selection shaped regional mtDNA variation in humans.

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