Ignoring heterozygous sites biases phylogenomic estimates of divergence times: implications for the evolutionary history of Microtus voles

Lischer, Heidi; Excoffier, Laurent; Heckel, Gerald (2014). Ignoring heterozygous sites biases phylogenomic estimates of divergence times: implications for the evolutionary history of Microtus voles. Molecular Biology and Evolution, 31(4), pp. 817-831. Oxford University Press 10.1093/molbev/mst271

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Phylogenetic reconstruction of the evolutionary history of closely related organisms may be difficult because of the presence of unsorted lineages and of a relatively high proportion of heterozygous sites that are usually not handled well by phylogenetic programs. Genomic data may provide enough fixed polymorphisms to resolve phylogenetic trees, but the diploid nature of sequence data remains analytically challenging. Here, we performed a phylogenomic reconstruction of the evolutionary history of the common vole (Microtus arvalis) with a focus on the influence of heterozygosity on the estimation of intraspecific divergence times. We used genome-wide sequence information from 15 voles distributed across the European range. We provide a novel approach to integrate heterozygous information in existing phylogenetic programs by repeated random haplotype sampling from sequences with multiple unphased heterozygous sites. We evaluated the impact of the use of full, partial, or no heterozygous information for tree reconstructions on divergence time estimates. All results consistently showed four deep and strongly supported evolutionary lineages in the vole data. These lineages undergoing divergence processes split only at the end or after the last glacial maximum based on calibration with radiocarbon-dated paleontological material. However, the incorporation of information from heterozygous sites had a significant impact on absolute and relative branch length estimations. Ignoring heterozygous information led to an overestimation of divergence times between the evolutionary lineages of M. arvalis. We conclude that the exclusion of heterozygous sites from evolutionary analyses may cause biased and misleading divergence time estimates in closely related taxa.

Item Type:

Journal Article (Original Article)


08 Faculty of Science > Department of Biology > Institute of Ecology and Evolution (IEE) > Population Genetics

UniBE Contributor:

Tschanz-Lischer, Heidi Erika Lisa, Excoffier, Laurent, Heckel, Gerald


500 Science > 570 Life sciences; biology




Oxford University Press




Isabelle Duperret

Date Deposited:

04 Sep 2015 07:53

Last Modified:

02 Mar 2023 23:26

Publisher DOI:






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