A Temporal Perspective on the Interplay of Demography and Selection on Deleterious Variation in Humans
When mutations have small effects on fitness, population size plays an important role in determining the amount and nature of deleterious genetic variation. The extent to which recent population size changes have impacted deleterious variation in humans has been a question of considerable interest a...
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| Format: | Article |
| Language: | English |
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Oxford University Press
2017-03-01
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| Series: | G3: Genes, Genomes, Genetics |
| Subjects: | |
| Online Access: | http://g3journal.org/lookup/doi/10.1534/g3.117.039651 |
| _version_ | 1818823692183928832 |
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| author | Evan Koch John Novembre |
| author_facet | Evan Koch John Novembre |
| author_sort | Evan Koch |
| collection | DOAJ |
| description | When mutations have small effects on fitness, population size plays an important role in determining the amount and nature of deleterious genetic variation. The extent to which recent population size changes have impacted deleterious variation in humans has been a question of considerable interest and debate. An emerging consensus is that the Out-of-Africa bottleneck and subsequent growth events have been too short to cause meaningful differences in genetic load between populations; though changes in the number and average frequencies of deleterious variants have taken place. To provide more support for this view and to offer additional insight into the divergent evolution of deleterious variation across populations, we numerically solve time-inhomogeneous diffusion equations and study the temporal dynamics of the frequency spectra in models of population size change for modern humans. We observe how the response to demographic change differs by the strength of selection, and we then assess whether similar patterns are observed in exome sequence data from 33,370 and 5203 individuals of non-Finnish European and West African ancestry, respectively. Our theoretical results highlight how even simple summaries of the frequency spectrum can have complex responses to demographic change. These results support the finding that some apparent discrepancies between previous results have been driven by the behaviors of the precise summaries of deleterious variation. Further, our empirical results make clear the difficulty of inferring slight differences in frequency spectra using recent next-generation sequence data. |
| first_indexed | 2024-12-18T23:44:01Z |
| format | Article |
| id | doaj.art-eb56456bbfb64f6996bc15440ce4ea32 |
| institution | Directory Open Access Journal |
| issn | 2160-1836 |
| language | English |
| last_indexed | 2024-12-18T23:44:01Z |
| publishDate | 2017-03-01 |
| publisher | Oxford University Press |
| record_format | Article |
| series | G3: Genes, Genomes, Genetics |
| spelling | doaj.art-eb56456bbfb64f6996bc15440ce4ea322022-12-21T20:47:17ZengOxford University PressG3: Genes, Genomes, Genetics2160-18362017-03-01731027103710.1534/g3.117.03965126A Temporal Perspective on the Interplay of Demography and Selection on Deleterious Variation in HumansEvan KochJohn NovembreWhen mutations have small effects on fitness, population size plays an important role in determining the amount and nature of deleterious genetic variation. The extent to which recent population size changes have impacted deleterious variation in humans has been a question of considerable interest and debate. An emerging consensus is that the Out-of-Africa bottleneck and subsequent growth events have been too short to cause meaningful differences in genetic load between populations; though changes in the number and average frequencies of deleterious variants have taken place. To provide more support for this view and to offer additional insight into the divergent evolution of deleterious variation across populations, we numerically solve time-inhomogeneous diffusion equations and study the temporal dynamics of the frequency spectra in models of population size change for modern humans. We observe how the response to demographic change differs by the strength of selection, and we then assess whether similar patterns are observed in exome sequence data from 33,370 and 5203 individuals of non-Finnish European and West African ancestry, respectively. Our theoretical results highlight how even simple summaries of the frequency spectrum can have complex responses to demographic change. These results support the finding that some apparent discrepancies between previous results have been driven by the behaviors of the precise summaries of deleterious variation. Further, our empirical results make clear the difficulty of inferring slight differences in frequency spectra using recent next-generation sequence data.http://g3journal.org/lookup/doi/10.1534/g3.117.039651deleterious variationdemographyhuman geneticsnearly neutral theoryselection |
| spellingShingle | Evan Koch John Novembre A Temporal Perspective on the Interplay of Demography and Selection on Deleterious Variation in Humans G3: Genes, Genomes, Genetics deleterious variation demography human genetics nearly neutral theory selection |
| title | A Temporal Perspective on the Interplay of Demography and Selection on Deleterious Variation in Humans |
| title_full | A Temporal Perspective on the Interplay of Demography and Selection on Deleterious Variation in Humans |
| title_fullStr | A Temporal Perspective on the Interplay of Demography and Selection on Deleterious Variation in Humans |
| title_full_unstemmed | A Temporal Perspective on the Interplay of Demography and Selection on Deleterious Variation in Humans |
| title_short | A Temporal Perspective on the Interplay of Demography and Selection on Deleterious Variation in Humans |
| title_sort | temporal perspective on the interplay of demography and selection on deleterious variation in humans |
| topic | deleterious variation demography human genetics nearly neutral theory selection |
| url | http://g3journal.org/lookup/doi/10.1534/g3.117.039651 |
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