Evolution by gene loss

Journal name:
Nature Reviews Genetics
Volume:
17,
Pages:
379–391
Year published:
DOI:
doi:10.1038/nrg.2016.39
Published online

Abstract

The recent increase in genomic data is revealing an unexpected perspective of gene loss as a pervasive source of genetic variation that can cause adaptive phenotypic diversity. This novel perspective of gene loss is raising new fundamental questions. How relevant has gene loss been in the divergence of phyla? How do genes change from being essential to dispensable and finally to being lost? Is gene loss mostly neutral, or can it be an effective way of adaptation? These questions are addressed, and insights are discussed from genomic studies of gene loss in populations and their relevance in evolutionary biology and biomedicine.

At a glance

Figures

  1. The wingless (Wnt) family: a paradigmatic example of the pervasiveness of gene loss during metazoan evolution.
    Figure 1: The wingless (Wnt) family: a paradigmatic example of the pervasiveness of gene loss during metazoan evolution.

    In the past decade, the accumulation of fully sequenced genome data from various species has revealed great heterogeneity in the dynamics of gene loss within different animal groups. In ecdysoazoans, for instance, not all insects show the same rate of gene loss, and European honeybees (Apis mellifera) seem to have retained more genes than other insects (for example, species of fly and mosquito in the Diptera order)206. The finding, for instance, of an active DNA CpG methylation toolkit (that is, Dnmt1, Dnm3a, Dnmt3b and Mdb) in honeybees was particularly remarkable, as it has been lost in most other insects207, 208. To date, the red flour beetle (Tribolium casteneum) has preserved the largest number of patchy orthologues that are also present in humans but that were lost in all other sequenced insects209. The genomes of crustaceans and myriapods showed less gene loss, and these groups conserved more universal bilaterian genes than insects151, 210. In lophotrocozoans, gene loss propensity is also heterogeneous among species. Mollusc gastropods, such as Lottia gigantea or annelids, such as Capitella teleta or Helobdella robusta, seem to have rates of gene retention similar to those in deuterostomes8, whereas other lophotrocozoans, such as the flatworm Schmidtea mediterranea, have lost approximately 40% of the ancestral gene families8, 171. Extensive gene loss (red boxes) has affected all Wnt gene subfamilies (1 to 11; 16 and A) throughout all metazoan taxa. Some gene losses seem to be ancestral (red circles) and thereby probably relevant for the evolution of entire groups (for example, ancestral loss of Wnt3 in the stem protostome). Other gene losses seem to occur recurrently in diverse lineages and show a patchy distribution (for example, Wnt11 loss in some chordates, echinoderms, arthropods, nematodes, molluscs and sponges). Controversial animal phylogenies (dashed tree branches)211, 212 or uncertain gene orthologies (nd) hinder the ability to determine whether the absence of Wnt families in most basal metazoans (grey boxes) is due to gene losses or to gene gains. References for the list of Wnt genes in each species are supplied in Supplementary information S3 (box).

  2. Conceptual framework for gene loss.
    Figure 2: Conceptual framework for gene loss.

    The loss of a gene depends on the degree of dispensability of the gene, which in turn depends on how fitness is affected by its non-functionalization. In a mutational robust system, either because of the presence of redundant genes or alternative pathways, mutations will have less impact on the fitness, therefore increasing the overall level of gene dispensability and facilitating gene loss. Gene functions are not equally essential in all environments and, therefore, environmental variability can also modify gene dispensability. Non-functionalization of a dispensable gene can either be neutral (or nearly neutral) when the gene is not needed, for instance in a new environmental condition (for example, regressive evolution), or it can can be adaptive if the loss of the function is advantageous in the new condition (for example, if it provides resistance to a disease: the less-is-more hypothesis). Finally, the balance between genetic drift, which depends on the population size, and selection will determine the probability of the fixation of gene loss.

  3. Biased patterns of gene loss.
    Figure 3: Biased patterns of gene loss.

    Gene loss patterns do not seem to follow stochastic fashions, but they show clear biases related to gene function (green) or genomic position (orange). These biased patterns are mainly caused by different constraints associated with gene dispensability related to Gene Ontology (GO) categories (blue) and constraints associated with the duplication mode that precedes gene losses (red). Genes from certain GO categories are more prone to be lost in certain species than others owing to differences in biological and environmental constraints (1). Relaxation of these constraints in certain species can lead to co-elimination of genes that are functionally linked in distinct pathways or complexes (2). Duplication-resistant genes from certain GO categories that have essential cellular functions, that are highly expressed or that are sensitive to dosage balance are prone to be lost after duplication in most organisms (3). Considering that small-scale duplication (SSD), but not whole-genome duplication (WGD), alters gene stoichiometry, duplication modes bias gene loss patterns towards certain GO categories, depending on their sensitivity to dosage balance (4). After WGD, gene losses are frequently asymmetrically distributed between ohnologons (Ohn), probably owing to enrichment of genes with high levels of transcription, dose-sensitive genes, genes with coordinated transcriptional regulation and genes that code for cis-protein–protein interacting (PPI) products (5). An extreme case of asymmetric distribution of gene loss occurs during the evolution of sex chromosomes, in which Y chromosomes (ChrY) are often depleted of most genes that were once shared with the X chromosomes (ChrX; 6). Reciprocal distribution of gene losses between the ohnologons of species that diverged after WGD reduces the viability of hypothetical hybrids, contributing therefore to reproductive isolation (7).

  4. Gene loss catalogues in evolutionary biology and translational medicine.
    Figure 4: Gene loss catalogues in evolutionary biology and translational medicine.

    Comparisons of the catalogues of gene losses between different species could be useful in many fields of biology. In the field of evolutionary biology, a comprehensive gene loss catalogue that covers a wide range of diverse groups of organisms can provide specific values of gene loss rate (GLR)213 and propensity for gene loss (PGL)214, which could help inference of the dispensability of any given gene during the evolution of any group of organisms (1). In addition, the identification of patterns of gene co-elimination make gene loss catalogues useful for predicting the functional connectivity of each gene within gene network modules or protein complexes215 (2). Manifested recurrent and convergent patterns of gene loss in different species that evolve under similar changes of ecological conditions (for example, light exposure, temperature, salinity, food, toxic substances or pathogens) could lead to the discovery of cases of adaptive gene loss associated with those environmental changes (3). In the field of translational medicine, a gene loss database could help in improving functional connectivity between model organisms and human genomes by distinguishing orthologous from paralogous genes in the setting of reciprocal gene loss175 (4) and could also help in the discovery of animals that are 'evolutionary knockouts' for genes related to human pathologies (5). These animals could become new disease models, as has already occurred for: the Antarctic icefish, which is a model for anaemia, osteoporosis and lipid storage disorders; the swordtail fish, which is a model for melanoma; the East African cichlid fish and Darwin's finches, which are models for craniofacial disease; some reptilian species, which are models for heterotopic ossification; and cavefish, which are models for retinal degeneration, cataracts, albinism and diabetes (as reviewed in Refs 216,217). Finally, comparison of gene loss catalogues between organisms that have suffered convergent processes of regressive evolution in structures or biological processes related to a human disease will help in discerning new candidate genes for diseases (6), as has already been demonstrated for the BBS5 gene in Bardet–Biedl ciliopathic syndrome (as reviewed in Ref. 13).

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Affiliations

  1. Departament de Genètica, Microbiologia i Estadística and Institut de Recerca de la Biodiversitat (IRBio), Facultat de Biologia, Universitat de Barcelona, Av. Diagonal 643, 08028 Barcelona, Spain.

    • Ricard Albalat &
    • Cristian Cañestro

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  • Ricard Albalat

    Ricard Albalat is an associate professor in the Department of Genetics and a member of the Biodiversity Research Institute (IRBio) at the Universitat de Barcelona, Spain. He began his research career investigating the evolution of several gene families in Drosophila spp., before switching to analysing similar gene families in chordates. He has also investigated the impact of transposable elements and the evolution of epigenetics mechanisms in chordate genomes. His recent work has focused on the effect of gene losses on the evolution of developmental gene networks in chordates by comparative studies between vertebrates and the urochordate Oikopleura dioica. This emergent model animal has suffered an extreme genome compaction accompanied of massive gene loss events. Ricard Albalat's homepage

  • Cristian Cañestro

    Cristian Cañestro is an associate professor in the Department of Genetics and a member of the Biodiversity Research Institute (IRBio) at the Universitat de Barcelona, Spain. His research experience is in the fields of evo–devo and genomics. During his career, he has studied several animal models — amphioxus, ascidians, larvaceans and zebrafish — to investigate the origin and evolution of our phylum, the chordates, and to develop models for human diseases. Currently, the work of his laboratory focuses on the study of Oikopleura dioica as a model for investigating the impact of gene loss on evo–devo, paying special attention to the heart, nervous system and maternal effect. O. dioica is also used as a model for exploring the power of gene loss as an adaptive evolutionary force for rapidly changing environments in the context of global warming. Cristian Cañestro's homepage

Supplementary information

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  1. Supplementary information S1 (table) (105 KB)

    Examples of gene losses associated to parasitic/endosymbiontic life styles

  2. Supplementary information S2 (table) (121 KB)

    Examples of gene losses in animals concomitant with the evolution of new biological features

  3. Supplementary information S3 (box) (81 KB)

    Supplementary information

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