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      Estimating ancestry and heterozygosity of hybrids using molecular markers

      research-article
      1 , 2 ,
      BMC Evolutionary Biology
      BioMed Central

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          Abstract

          Background

          Hybridization, genetic mixture of distinct populations, gives rise to myriad recombinant genotypes. Characterizing the genomic composition of hybrids is critical for studies of hybrid zone dynamics, inheritance of traits, and consequences of hybridization for evolution and conservation. Hybrid genomes are often summarized either by an estimate of the proportion of alleles coming from each ancestral population or classification into discrete categories like F1, F2, backcross, or merely “hybrid” vs. “pure”. In most cases, it is not realistic to classify individuals into the restricted set of classes produced in the first two generations of admixture. However, the continuous ancestry index misses an important dimension of the genotype. Joint consideration of ancestry together with interclass heterozygosity (proportion of loci with alleles from both ancestral populations) captures all of the information in the discrete classification without the unrealistic assumption that only two generations of admixture have transpired.

          Methods

          I describe a maximum likelihood method for joint estimation of ancestry and interclass heterozygosity. I present two worked examples illustrating the value of the approach for describing variation among hybrid populations and evaluating the validity of the assumption underlying discrete classification.

          Results

          Naively classifying natural hybrids into the standard six line cross categories can be misleading, and false classification can be a serious problem for datasets with few molecular markers. My analysis underscores previous work showing that many (50 or more) ancestry informative markers are needed to avoid erroneous classification.

          Conclusion

          Although classification of hybrids might often be misleading, valuable inferences can be obtained by focusing directly on distributions of ancestry and heterozygosity. Estimating and visualizing the joint distribution of ancestry and interclass heterozygosity is an effective way to compare the genetic structure of hybrid populations and these estimates can be used in classic quantitative genetic methods for assessing additive, dominant, and epistatic genetic effects on hybrid phenotypes and fitness. The methods are implemented in a freely available package “HIest” for the R statistical software ( http://cran.r-project.org/web/packages/HIest/index.html).

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          Most cited references23

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          Speciation by hybridization in Heliconius butterflies.

          Speciation is generally regarded to result from the splitting of a single lineage. An alternative is hybrid speciation, considered to be extremely rare, in which two distinct lineages contribute genes to a daughter species. Here we show that a hybrid trait in an animal species can directly cause reproductive isolation. The butterfly species Heliconius heurippa is known to have an intermediate morphology and a hybrid genome, and we have recreated its intermediate wing colour and pattern through laboratory crosses between H. melpomene, H. cydno and their F1 hybrids. We then used mate preference experiments to show that the phenotype of H. heurippa reproductively isolates it from both parental species. There is strong assortative mating between all three species, and in H. heurippa the wing pattern and colour elements derived from H. melpomene and H. cydno are both critical for mate recognition by males.
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            A fine-scale chimpanzee genetic map from population sequencing.

            To study the evolution of recombination rates in apes, we developed methodology to construct a fine-scale genetic map from high-throughput sequence data from 10 Western chimpanzees, Pan troglodytes verus. Compared to the human genetic map, broad-scale recombination rates tend to be conserved, but with exceptions, particularly in regions of chromosomal rearrangements and around the site of ancestral fusion in human chromosome 2. At fine scales, chimpanzee recombination is dominated by hotspots, which show no overlap with those of humans even though rates are similarly elevated around CpG islands and decreased within genes. The hotspot-specifying protein PRDM9 shows extensive variation among Western chimpanzees, and there is little evidence that any sequence motifs are enriched in hotspots. The contrasting locations of hotspots provide a natural experiment, which demonstrates the impact of recombination on base composition.
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              Different differences: the use of 'genetic ancestry' versus race in biomedical human genetic research.

              This article presents findings from our ethnographic research on biomedical scientists' studies of human genetic variation and common complex disease. We examine the socio-material work involved in genome-wide association studies (GWAS) and discuss whether, how, and when notions of race and ethnicity are or are not used. We analyze how researchers produce simultaneously different kinds of populations and population differences. Although many geneticists use race in their analyses, we find some who have invented a statistical genetics method and associated software that they use specifically to avoid using categories of race in their genetic analysis. Their method allows them to operationalize their concept of 'genetic ancestry' without resorting to notions of race and ethnicity. We focus on the construction and implementation of the software's algorithms, and discuss the consequences and implications of the software technology for debates and policies around the use of race in genetics research. We also demonstrate that the production and use of their method involves a dynamic and fluid assemblage of actors in various disciplines responding to disciplinary and sociopolitical contexts and concerns. This assemblage also includes particular discourses on human history and geography as they become entangled with research on genetic markers and disease.We introduce the concept of'genome geography' to analyze how some researchers studying human genetic variation'locate' stretches of DNA in different places and times. The concept of genetic ancestry and the practice of genome geography rely on old discourses, but they also incorporate new technologies, infrastructures, and political and scientific commitments. Some of these new technologies provide opportunities to change some of our institutional and cultural forms and frames around notions of difference and similarity. Nevertheless, we also highlight the slipperiness of genome geography and the tenacity of race and race concepts.
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                Author and article information

                Contributors
                Journal
                BMC Evol Biol
                BMC Evol. Biol
                BMC Evolutionary Biology
                BioMed Central
                1471-2148
                2012
                31 July 2012
                : 12
                : 131
                Affiliations
                [1 ]Department of Ecology and Evolutionary Biology, University of Tennessee, Knoxville, TN 37996, USA
                [2 ]National Institute for Mathematical and Biological Synthesis, Knoxville, TN 37996, USA
                Article
                1471-2148-12-131
                10.1186/1471-2148-12-131
                3572440
                22849298
                08ad85be-a908-4bfc-833f-f5f9313d3ca6
                Copyright ©2012 Fitzpatrick; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 May 2012
                : 13 July 2012
                Categories
                Methodology Article

                Evolutionary Biology
                Evolutionary Biology

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