Intergenomic epistasis causes asynchronous hatch times in whitefish hybrids, but only when parental ecotypes differ

Support for the theory of ecological speciation requires evidence for ecological divergence between species which directly or indirectly causes reproductive isolation. This study investigates effects of ecological vs. genetic disparity of parental species on the presence of endogenous selection (deformation and mortality rates) and potential sources of exogenous selection (growth rates and hatch timing) on hybrids. Hybrid embryonic development is analysed in a common-garden full-sib cross of three species belonging to two different ecotypes within the Coregonus lavaretus species flock in the central Alpine region of Europe. Although hatch timing was similar across the three species, embryonic growth rates and egg sizes differed between ecotypes. This led to a mismatch between embryonic growth rate and egg size in hybrid crosses that reveals epistasis between the maternal and embryonic genomes and transgressive hatch times that were asynchronous with control crosses. A strong constraint of egg size to embryo size at late development was also evident. We argue that this demonstrates potential for coadaptation of a maternal trait (egg size) with offspring growth rate to be an important source of selection against hybridization between ecotypes with different egg sizes. Implications for the measurement and quantification of early life-history traits affected by this additive relationship, such as hatch day and larval size, are also discussed.

Mechanisms of species divergence through visual adaptation and sexual selection: Perspectives from a cichlid model system

The theory of ecological speciation suggests that assortative mating evolves most easily when mating preferences are;directly linked to ecological traits that are subject to divergent selection. Sensory adaptation can play a major role in this process,;because selective mating is often mediated by sexual signals: bright colours, complex song, pheromone blends and so on. When;divergent sensory adaptation affects the perception of such signals, mating patterns may change as an immediate consequence.;Alternatively, mating preferences can diverge as a result of indirect effects: assortative mating may be promoted by selection;against intermediate phenotypes that are maladapted to their (sensory) environment. For Lake Victoria cichlids, the visual environment;constitutes an important selective force that is heterogeneous across geographical and water depth gradients. We investigate;the direct and indirect effects of this heterogeneity on the evolution of female preferences for alternative male nuptial colours;(red and blue) in the genus Pundamilia. Here, we review the current evidence for divergent sensory drive in this system, extract;general principles, and discuss future perspectives

Structure and dynamics of hybrid zones at different stages of speciation in the common vole (Microtus arvalis)

The genetic structure and dynamics of hybrid zones provide crucial information for understanding the processes and mechanisms of evolutionary divergence and speciation. In general, higher levels of evolutionary divergence between taxa are more likely to be associated with reproductive isolation and may result in suppressed or strongly restricted hybridization. In this study, we examined two secondary contact zones between three deep evolutionary lineages in the common vole (Microtus arvalis). Differences in divergence times between the lineages can shed light on different stages of reproductive isolation and thus provide information on the ongoing speciation process in M. arvalis. We examined more than 800 individuals for mitochondrial (mtDNA), Y-chromosome and autosomal markers and used assignment and cline analysis methods to characterize the extent and direction of gene flow in the contact zones. Introgression of both autosomal and mtDNA markers in a relatively broad area of admixture indicates selectively neutral hybridization between the least-divergent lineages (Central and Eastern) without evidence for partial reproductive isolation. In contrast, a very narrow area of hybridization, shifts in marker clines and the quasi-absence of Y-chromosome introgression support a moving hybrid zone and unidirectional selection against male hybrids between the lineages with older divergence (Central and Western). Data from a replicate transect further support non-neutral processes in this hybrid zone and also suggest a role for landscape history in the movement and shaping of geneflow profiles.

Tracing reinforcement through asymmetrical partner preference in the European common vole Microtus arvalis

Background The mechanistic basis of speciation and in particular the contribution of behaviour to the completion of the speciation process is often contentious. Contact zones between related taxa provide a situation where selection against hybridization might reinforce separation by behavioural mechanisms, which could ultimately fully isolate the taxa. One of the most abundant European mammals, the common vole Microtus arvalis, forms multiple natural hybrid zones where rapidly diverging evolutionary lineages meet in secondary contact. Very narrow zones of hybridization spanning only a few kilometres and sex-specific gene flow patterns indicate reduced fitness of natural hybrids and incipient speciation between some of the evolutionary lineages. In this study, we examined the contribution of behavioural mechanisms to the speciation process in these rodents by fine-mapping allopatric and parapatric populations in the hybrid zone between the Western and Central lineages and experimental testing of the partner preferences of wild, pure-bred and hybrid female common voles. Results Genetic analysis based on microsatellite markers revealed the presence of multiple parapatric and largely non-admixed populations at distances of about 10 km at the edge of the area of natural hybridization between the Western and Central lineages. Wild females from Western parapatric populations and lab-born F1 hybrids preferred males from the Western lineage whereas wild females of Central parapatric origin showed no measurable preference. Furthermore, wild and lab-born females from allopatric populations of the Western or Central lineages showed no detectable preference for males from either lineage. Conclusions The detected partner preferences are consistent with asymmetrical reinforcement of pre-mating reproductive isolation mechanisms in the European common vole and with earlier results suggesting that hybridization is more detrimental to the Western lineage. As a consequence, these differences in behaviour might contribute to a further geographical stabilization of this moving hybrid zone. Such behavioural processes could also provide a mechanistic perspective for frequently-detected asymmetrical introgression patterns in the largely allopatrically diversifying Microtus genus and other rapidly speciating rodents.

Avoidance of Long Mononucleotide Repeats in Codon Pair Usage

Protein is an essential component for life, and its synthesis is mediated by codons in any organisms on earth. While some codons encode the same amino acid, their usage is often highly biased. There are many factors that can cause the bias, but a potential effect of mononucleotide repeats, which are known to be highly mutable, on codon usage and codon pair preference is largely unknown. In this study we performed a genomic survey on the relationship between mononucleotide repeats and codon pair bias in 53 bacteria, 68 archaea, and 13 eukaryotes. By distinguishing the codon pair bias from the codon usage bias, four general patterns were revealed: strong avoidance of five or six mononucleotide repeats in codon pairs; lower observed/expected (o/e) ratio for codon pairs with C or G repeats (C/G pairs) than that with A or T repeats (A/T pairs); a negative correlation between genomic GC contents and the o/e ratios, particularly for C/G pairs; and avoidance of C/G pairs in highly conserved genes. These results support natural selection against long mononucleotide repeats, which could induce frameshift mutations in coding sequences. The fact that these patterns are found in all kingdoms of life suggests that this is a general phenomenon in living organisms. Thus, long mononucleotide repeats may play an important role in base composition and genetic stability of a gene and gene functions.

Thermal adaptation and ecological speciation

Ecological speciation is defined as the emergence of reproductive isolation as a direct or indirect consequence of divergent ecological adaptation. Several empirical examples of ecological speciation have been reported in the literature which very often involve adaptation to biotic resources. In this review, we investigate whether adaptation to different thermal habitats could also promote speciation and try to assess the importance of such processes in nature. Our survey of the literature identified 16 animal and plant systems where divergent thermal adaptation may underlie (partial) reproductive isolation between populations or may allow the stable coexistence of sibling taxa. In many of the systems, the differentially adapted populations have a parapatric distribution along an environmental gradient. Isolation often involves extrinsic selection against locally maladapted parental or hybrid genotypes, and additional pre- or postzygotic barriers may be important. Together, the identified examples strongly suggest that divergent selection between thermal environments is often strong enough to maintain a bimodal genotype distribution upon secondary contact. What is less clear from the available data is whether it can also be strong enough to allow ecological speciation in the face of gene flow through reinforcement-like processes. It is possible that intrinsic features of thermal gradients or the genetic basis of thermal adaptation make such reinforcement-like processes unlikely but it is equally possible that pertinent systems are understudied. Overall, our literature survey highlights (once again) the dearth of studies that investigate similar incipient species along the continuum from initial divergence to full reproductive isolation and studies that investigate all possible reproductive barriers in a given system.

Microphthalmia in Texel sheep is associated with a missense mutation in the paired-like homeodomain 3 (PITX3) gene

Microphthalmia in sheep is an autosomal recessive inherited congenital anomaly found within the Texel breed. It is characterized by extremely small or absent eyes and affected lambs are absolutely blind. For the first time, we use a genome-wide ovine SNP array for positional cloning of a Mendelian trait in sheep. Genotyping 23 cases and 23 controls using Illumina's OvineSNP50 BeadChip allowed us to localize the causative mutation for microphthalmia to a 2.4 Mb interval on sheep chromosome 22 by association and homozygosity mapping. The PITX3 gene is located within this interval and encodes a homeodomain-containing transcription factor involved in vertebrate lens formation. An abnormal development of the lens vesicle was shown to be the primary event in ovine microphthalmia. Therefore, we considered PITX3 a positional and functional candidate gene. An ovine BAC clone was sequenced, and after full-length cDNA cloning the PITX3 gene was annotated. Here we show that the ovine microphthalmia phenotype is perfectly associated with a missense mutation (c.338G>C, p.R113P) in the evolutionary conserved homeodomain of PITX3. Selection against this candidate causative mutation can now be used to eliminate microphthalmia from Texel sheep in production systems. Furthermore, the identification of a naturally occurring PITX3 mutation offers the opportunity to use the Texel as a genetically characterized large animal model for human microphthalmia.

A deletion in the N-myc downstream regulated gene 1 (NDRG1) gene in Greyhounds with polyneuropathy

The polyneuropathy of juvenile Greyhound show dogs shows clinical similarities to the genetically heterogeneous Charcot-Marie-Tooth (CMT) disease in humans. The pedigrees containing affected dogs suggest monogenic autosomal recessive inheritance and all affected dogs trace back to a single male. Here, we studied the neuropathology of this disease and identified a candidate causative mutation. Peripheral nerve biopsies from affected dogs were examined using semi-thin histology, nerve fibre teasing and electron microscopy. A severe chronic progressive mixed polyneuropathy was observed. Seven affected and 17 related control dogs were genotyped on the 50k canine SNP chip. This allowed us to localize the causative mutation to a 19.5 Mb interval on chromosome 13 by homozygosity mapping. The NDRG1 gene is located within this interval and NDRG1 mutations have been shown to cause hereditary motor and sensory neuropathy-Lom in humans (CMT4D). Therefore, we considered NDRG1 a positional and functional candidate gene and performed mutation analysis in affected and control Greyhounds. A 10 bp deletion in canine NDRG1 exon 15 (c.1080_1089delTCGCCTGGAC) was perfectly associated with the polyneuropathy phenotype of Greyhound show dogs. The deletion causes a frame shift (p.Arg361SerfsX60) which alters several amino acids before a stop codon is encountered. A reduced level of NDRG1 transcript could be detected by RT-PCR. Western blot analysis demonstrated an absence of NDRG1 protein in peripheral nerve biopsy of an affected Greyhound. We thus have identified a candidate causative mutation for polyneuropathy in Greyhounds and identified the first genetically characterized canine CMT model which offers an opportunity to gain further insights into the pathobiology and therapy of human NDRG1 associated CMT disease. Selection against this mutation can now be used to eliminate polyneuropathy from Greyhound show dogs.

PU.1 binding to the p53 family of tumor suppressors impairs their transcriptional activity

The transcription factor PU.1 is essential for terminal myeloid differentiation, B- and T-cell development, erythropoiesis and hematopoietic stem cell maintenance. PU.1 functions as oncogene in Friend virus-induced erythroleukemia and as tumor suppressor in acute myeloid leukemias. Moreover, Friend virus-induced erythroleukemia requires maintenance of PU.1 expression and the disruption of p53 function greatly accelerates disease progression. It has been hypothesized that p53-mediated expression of the p21(Cip1) cell cycle inhibitor during differentiation of pre-erythroleukemia cells promotes selection against p53 function. In addition to the blockage of erythroblast differentiation provided by increased levels of PU.1, we propose that PU.1 alters p53 function. We demonstrate that PU.1 reduces the transcriptional activity of the p53 tumor suppressor family and thus inhibits activation of genes important for cell cycle regulation and apoptosis. Inhibition is mediated through binding of PU.1 to the DNA-binding and/or oligomerization domains of p53/p73 proteins. Lastly, knocking down endogenous PU.1 in p53 wild-type REH B-cell precursor leukemia cells leads to increased expression of the p53 target p21(Cip1).

A non-coding genomic duplication at the HMX1 locus is associated with crop ears in highland cattle.

Highland cattle with congenital crop ears have notches of variable size on the tips of both ears. In some cases, cartilage deformation can be seen and occasionally the external ears are shortened. We collected 40 cases and 80 controls across Switzerland. Pedigree data analysis confirmed a monogenic autosomal dominant mode of inheritance with variable expressivity. All affected animals could be traced back to a single common ancestor. A genome-wide association study was performed and the causative mutation was mapped to a 4 Mb interval on bovine chromosome 6. The H6 family homeobox 1 (HMX1) gene was selected as a positional and functional candidate gene. By whole genome re-sequencing of an affected Highland cattle, we detected 6 non-synonymous coding sequence variants and two variants in an ultra-conserved element at the HMX1 locus with respect to the reference genome. Of these 8 variants, only a non-coding 76 bp genomic duplication (g.106720058_106720133dup) located in the conserved region was perfectly associated with crop ears. The identified copy number variation probably results in HMX1 misregulation and possible gain-of-function. Our findings confirm the role of HMX1 during the development of the external ear. As it is sometimes difficult to phenotypically diagnose Highland cattle with slight ear notches, genetic testing can now be used to improve selection against this undesired trait.

A Gly98Val mutation in the N-Myc downstream regulated gene 1 (NDRG1) in Alaskan Malamutes with polyneuropathy.

The first cases of early-onset progressive polyneuropathy appeared in the Alaskan Malamute population in Norway in the late 1970s. Affected dogs were of both sexes and were ambulatory paraparetic, progressing to non-ambulatory tetraparesis. On neurologic examination, affected dogs displayed predominantly laryngeal paresis, decreased postural reactions, decreased spinal reflexes and muscle atrophy. The disease was considered eradicated through breeding programmes but recently new cases have occurred in the Nordic countries and the USA. The N-myc downstream-regulated gene (NDRG1) is implicated in neuropathies with comparable symptoms or clinical signs both in humans and in Greyhound dogs. This gene was therefore considered a candidate gene for the polyneuropathy in Alaskan Malamutes. The coding sequence of the NDRG1 gene derived from one healthy and one affected Alaskan Malamute revealed a non-synonymous G>T mutation in exon 4 in the affected dog that causes a Gly98Val amino acid substitution. This substitution was categorized to be "probably damaging" to the protein function by PolyPhen2 (score: 1.000). Subsequently, 102 Alaskan Malamutes from the Nordic countries and the USA known to be either affected (n = 22), obligate carriers (n = 7) or healthy (n = 73) were genotyped for the SNP using TaqMan. All affected dogs had the T/T genotype, the obligate carriers had the G/T genotype and the healthy dogs had the G/G genotype except for 13 who had the G/T genotype. A protein alignment showed that residue 98 is conserved in mammals and also that the entire NDRG1 protein is highly conserved (94.7%) in mammals. We conclude that the G>T substitution is most likely the mutation that causes polyneuropathy in Alaskan Malamutes. Our characterization of a novel candidate causative mutation for polyneuropathy offers a new canine model that can provide further insight into pathobiology and therapy of human polyneuropathy. Furthermore, selection against this mutation can now be used to eliminate the disease in Alaskan Malamutes.

A transposable element insertion in APOB causes cholesterol deficiency in Holstein cattle

Cholesterol deficiency, a new autosomal recessive inherited genetic defect in Holstein cattle, has been recently reported to have an influence on the rearing success of calves. The affected animals show unresponsive diarrhea accompanied by hypocholesterolemia and usually die within the first weeks or months of life. Here, we show that whole genome sequencing combined with the knowledge about the pedigree and inbreeding status of a livestock population facilitates the identification of the causative mutation. We resequenced the entire genomes of an affected calf and a healthy partially inbred male carrying one copy of the critical 2.24-Mb chromosome 11 segment in its ancestral state and one copy of the same segment with the cholesterol deficiency mutation. We detected a single structural variant, homozygous in the affected case and heterozygous in the non-affected carrier male. The genetic makeup of this key animal provides extremely strong support for the causality of this mutation. The mutation represents a 1.3kb insertion of a transposable LTR element (ERV2-1) in the coding sequence of the APOB gene, which leads to truncated transcripts and aberrant splicing. This finding was further supported by RNA sequencing of the liver transcriptome of an affected calf. The encoded apolipoprotein B is an essential apolipoprotein on chylomicrons and low-density lipoproteins, and therefore, the mutation represents a loss of function mutation similar to autosomal recessive inherited familial hypobetalipoproteinemia-1 (FHBL1) in humans. Our findings provide a direct gene test to improve selection against this deleterious mutation in Holstein cattle.

Tradeoffs associated with constitutive and induced plant resistance against herbivory

Several prominent hypotheses have been posed to explain the immense variability among plant species in defense against herbivores. A major concept in the evolutionary ecology of plant defenses is that tradeoffs of defense strategies are likely to generate and maintain species diversity. In particular, tradeoffs between constitutive and induced resistance and tradeoffs relating these strategies to growth and competitive ability have been predicted. We performed three independent experiments on 58 plant species from 15 different plant families to address these hypotheses in a phylogenetic framework. Because evolutionary tradeoffs may be altered by human-imposed artificial selection, we used 18 wild plant species and 40 cultivated garden-plant species. Across all 58 plant species, we demonstrate a tradeoff between constitutive and induced resistance, which was robust to accounting for phylogenetic history of the species. Moreover, the tradeoff was driven by wild species and was not evident for cultivated species. In addition, we demonstrate that more competitive species—but not fast growing ones—had lower constitutive but higher induced resistance. Thus, our multispecies experiments indicate that the competition–defense tradeoff holds for constitutive resistance and is complemented by a positive relationship of competitive ability with induced resistance. We conclude that the studied genetically determined tradeoffs are indeed likely to play an important role in shaping the high diversity observed among plant species in resistance against herbivores and in life history traits.