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Evaluating the ability of the pairwise joint site frequency spectrum to co-estimate selection and demography.

Mathew LA, Jensen JD - Front Genet (2015)

Bottom Line: Although it has been well-described that selection and demography may result in similar patterns of diversity, the ability to jointly estimate these two processes has remained elusive.We further demonstrate that the common assumption of selective neutrality when estimating demographic models may lead to severe biases.Finally, we apply the approach we have developed to better characterize the within-host demographic and selective history of human cytomegalovirus (HCMV) infection using published next generation sequencing data.

View Article: PubMed Central - PubMed

Affiliation: School of Life Sciences, École Polytechnique Fédérale de Lausanne Lausanne, Switzerland.

ABSTRACT
The ability to infer the parameters of positive selection from genomic data has many important implications, from identifying drug-resistance mutations in viruses to increasing crop yield by genetically integrating favorable alleles. Although it has been well-described that selection and demography may result in similar patterns of diversity, the ability to jointly estimate these two processes has remained elusive. Here, we use simulation to explore the utility of the joint site frequency spectrum to estimate selection and demography simultaneously, including developing an extension of the previously proposed Jaatha program (Mathew et al., 2013). We evaluate both complete and incomplete selective sweeps under an isolation-with-migration model with and without population size change (both population growth and bottlenecks). Results suggest that while it may not be possible to precisely estimate the strength of selection, it is possible to infer the presence of selection while estimating accurate demographic parameters. We further demonstrate that the common assumption of selective neutrality when estimating demographic models may lead to severe biases. Finally, we apply the approach we have developed to better characterize the within-host demographic and selective history of human cytomegalovirus (HCMV) infection using published next generation sequencing data.

No MeSH data available.


Related in: MedlinePlus

In both demographic models used for the simulation study – Constant and SizeChange – one ancestral population splits into two daughter populations at time τ followed by continuous, bidirectional gene flow. Selection is simulated by introducing a single selected site at the time of the split in the second population only (marked in red; for more details see text).
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Figure 1: In both demographic models used for the simulation study – Constant and SizeChange – one ancestral population splits into two daughter populations at time τ followed by continuous, bidirectional gene flow. Selection is simulated by introducing a single selected site at the time of the split in the second population only (marked in red; for more details see text).

Mentions: We investigate two models – an ongoing sweep and a completed sweep – under two demographic models involving a population split (Figure 1). In both models, population P1 (with θ = 4Neμ with Ne being the effective population size of P1) stays constant in size after the split from the ancestral population. The ancestral population of size (1+u)Ne splits at τ generations (measured in units of 4Ne) before the present into two populations. In the Constant model P2 stays unchanged in size after the split (i.e., u = q). In the SizeChange model P2 exponentially changes its size from uNe to qNe and u = 0.3; thus if q > 0.3, P2 increases in size following the split. Migration is assumed to be symmetric between P1 and P2 and is also measured in units of 4Ne, as in msms (Ewing and Hermisson, 2010).


Evaluating the ability of the pairwise joint site frequency spectrum to co-estimate selection and demography.

Mathew LA, Jensen JD - Front Genet (2015)

In both demographic models used for the simulation study – Constant and SizeChange – one ancestral population splits into two daughter populations at time τ followed by continuous, bidirectional gene flow. Selection is simulated by introducing a single selected site at the time of the split in the second population only (marked in red; for more details see text).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4538300&req=5

Figure 1: In both demographic models used for the simulation study – Constant and SizeChange – one ancestral population splits into two daughter populations at time τ followed by continuous, bidirectional gene flow. Selection is simulated by introducing a single selected site at the time of the split in the second population only (marked in red; for more details see text).
Mentions: We investigate two models – an ongoing sweep and a completed sweep – under two demographic models involving a population split (Figure 1). In both models, population P1 (with θ = 4Neμ with Ne being the effective population size of P1) stays constant in size after the split from the ancestral population. The ancestral population of size (1+u)Ne splits at τ generations (measured in units of 4Ne) before the present into two populations. In the Constant model P2 stays unchanged in size after the split (i.e., u = q). In the SizeChange model P2 exponentially changes its size from uNe to qNe and u = 0.3; thus if q > 0.3, P2 increases in size following the split. Migration is assumed to be symmetric between P1 and P2 and is also measured in units of 4Ne, as in msms (Ewing and Hermisson, 2010).

Bottom Line: Although it has been well-described that selection and demography may result in similar patterns of diversity, the ability to jointly estimate these two processes has remained elusive.We further demonstrate that the common assumption of selective neutrality when estimating demographic models may lead to severe biases.Finally, we apply the approach we have developed to better characterize the within-host demographic and selective history of human cytomegalovirus (HCMV) infection using published next generation sequencing data.

View Article: PubMed Central - PubMed

Affiliation: School of Life Sciences, École Polytechnique Fédérale de Lausanne Lausanne, Switzerland.

ABSTRACT
The ability to infer the parameters of positive selection from genomic data has many important implications, from identifying drug-resistance mutations in viruses to increasing crop yield by genetically integrating favorable alleles. Although it has been well-described that selection and demography may result in similar patterns of diversity, the ability to jointly estimate these two processes has remained elusive. Here, we use simulation to explore the utility of the joint site frequency spectrum to estimate selection and demography simultaneously, including developing an extension of the previously proposed Jaatha program (Mathew et al., 2013). We evaluate both complete and incomplete selective sweeps under an isolation-with-migration model with and without population size change (both population growth and bottlenecks). Results suggest that while it may not be possible to precisely estimate the strength of selection, it is possible to infer the presence of selection while estimating accurate demographic parameters. We further demonstrate that the common assumption of selective neutrality when estimating demographic models may lead to severe biases. Finally, we apply the approach we have developed to better characterize the within-host demographic and selective history of human cytomegalovirus (HCMV) infection using published next generation sequencing data.

No MeSH data available.


Related in: MedlinePlus