Papers to discuss Spring 2016

This Spring, we have decided to have a few series of papers on related topics, to discuss one per week:

Series 1 (see also discussion on Razib Khan’s blog):

  1. Moorjani et al 2013 Genetic Evidence for Recent Population Mixture in India AJHG 93,: 422–438
  2. Basu et al 2016 Genomic reconstruction of the history of extant populations of India reveals five distinct ancestral components and a complex structure PNAS online before print
  3. van Dorp et al 2016 Evidence for a Common Origin of Blacksmiths and Cultivators in the Ethiopian Ari within the Last 4500 Years: Lessons for Clustering-Based Inference PLOS Genetics 11(8): e1005397

Series 2 (see also perspective in Science Magazine):

  1. Küpper et al 2016 A supergene determines highly divergent male reproductive morphs in the ruff Nature Genetics 48: 79–83
  2. Lamichhaney et al 2016 Structural genomic changes underlie alternative reproductive strategies in the ruff (Philomachus pugnax) Nature Genetics 48: 84–88

The following form less of a series (although two are sex-related):

  1. Pipoly et al 2015 The genetic sex-determination system predicts adult sex ratios in tetrapods Nature 527: 91–94
  2. Barson et al 2015 Sex-dependent dominance at a single locus maintains variation in age at maturity in salmon Nature 528: 405–408
  3. Sulem et al 2015 Identification of a large set of rare complete human knockouts Nature Genetics 47: 448–452

 

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Evolution of Darwin’s finches and their beaks revealed by genome sequencing

The recent formation and habitat diversity of the Galápagos archipelago, in conjunction with its relative isolation from the mainland, has helped the islands become rich in endemic species that have much to offer for the study of evolutionary biology.

As a result of their volcanic origin and fluctuating climates, the islands of the Galápagos archipelago vary in age, size, topography and vegetation. In conjunction with their isolation from the mainland, this diversity of relatively new environments, both within and between islands, are perfect breeding grounds for speciation. The finches of the Galápagos archipelago and Cocos Island are the product of a fascinating adaptive radiation that started only about 1.5 million years ago, following the arrival of a common ancestor from South America. These finches are most notable for their diversity in beak morphology, which reflect the differences in their respective adaptations to exploiting various food resources. Charles Darwin’s observations of this diversity in beak morphology played an important role in the development of his theory of natural selection.

“Seeing this gradation and diversity of structure in one small, intimately related group of birds, one might really fancy that from an original paucity of birds in this archipelago, one species had been taken and modified for different ends” – Charles Darwin

There has since been great interest in the study of Darwin’s finches, and much research has been done towards the efforts of resolving their phylogenetic history and elucidating the mechanisms that drive their variation. In the paper reviewed here, the authors took the extraordinary step of sequencing the whole genomes of 120 individuals, representing all 15 of the Darwin’s finch species across the Galápagos and Cocos Islands as well as two close relatives (Tiaris bicolor and Loxigilla noctis) from Barbados. Analyzing this rich data set, they find important deviations from previous taxonomies and identify several genomic regions associated with beak shape.

Phylogeny

Figure 1: (a) Sample locations and (b) phylogeny based on all autosomal sites

Figure 1: Sample locations and phylogeny based on all autosomal sequences

Species tree from F based largely on mitochondrial DNA

Species tree from Farrington et al. (2014)

After sequencing and assembly, they generated four phylogenies according to (i) autosomal DNA (see Figure 1 above), (ii) mitochondrial DNA and (iii, iv) sequences linked to sex chromosomes Z and W. Their phylogenies largely supported previous taxonomies (compare Figure 1 with the tree to the right, which was generated using 14 nuclear introns and two short sequences of mitochondrial DNA (Farrington et al., 2014). However, this new genome-based phylogeny also showed some important differences. For one, as we can see in figure 1 above, the species classified as G. difficilis actually forms three distinct groups, which cluster geographically by the islands of (1) Pinta, Santiago and Fernandina, (2) Wolf and Darwin and (3) Genovese. Apparently this is consistent with taxonomies proposed in two studies that appeared in 1931 and 1945, but it is unclear to me why they remained classified as a single species until now.

Similarly, they found that G. conirostris is likely also paraphyletic, given that G. conirostris on Española was most similar to G. magnirostris, and G. conirostris on Genovesa was most similar to G. scandens. Following these findings, the authors of this study recommend that the taxonomy for G. difficilis and G. conirostris be revised to reflect their paraphyly, according to the new genome-based phylogeny.

Gene flow

Evidence for introgression was found by comparing the autosomal phylogenetic tree with those of the sex-linked loci and mtDNA, and through ABBA-BABA tests. They found that there has been extensive gene flow and hybridization between the species throughout the radiation, which likely contributed to their rapid evolution.

While this is certainly a very interesting find, it is perhaps unsurprising, given the proximity of the islands and the relative ease for individuals to fly from one to the other. This does offer a nice comparison to the adaptive radiations of cichlid fishes, which occur in geographically isolated lakes without the opportunity for gene flow between them (see blog post).

Genetic basis of beak shape

Network tree of Darwin's finches showing diversity of beak shape

Network tree of Darwin’s finches with images showing diversity of beak shape

Now that they had this large genomic dataset, they wanted to address the question of how molecular differentiation contributes to beak morphology. They did this by choosing four closely related populations that differed in beak shape (two blunt and two pointed), and then scanned the whole genomes to identify regions with high genetic differentiation (Z-transformed FST, ZFST) between the two phenotypes. In figure 3a below, we can see that they have marked 15 regions with the highest ZFST values, along with the genes identified within them.Screen Shot 2015-06-01 at 11.14.08

Of those genes, they found 6 that were previously reported to be involved with craniofacial/beak development in mammals and birds. Interestingly, they did not find high genetic differentiation in bone morphogenetic protein 4 (BMP4), a gene that was previously reported to show differential expression between beak types. This may be due to differential expression, and it’s a pity this study does not include any RNA-seq work to complement their huge genomic dataset, but perhaps they’re saving that for another Nature.

Haplotype tree of the ALX1 region

Haplotype tree of the ALX1 region

The highest ZFST peak contained the gene ALX1, which is involved in craniofacial development, and whose loss in humans can even cause severe facial clefting. The authors found that two variants of this ALX1 gene are present, and each remarkably corresponds to one of two categories of beak shape: blunt and pointed. A phylogenetic tree constructed from this region (figure 3c left) shows that the blunt shape was an early adaptation that seems to have been quite favorable; the short branch lengths among the blunt haplotypes (red) are indicative of a selective sweep, which is further supported by the low nucleotide diversity shown in figure 3b below (although it looks as though G. difficilis from Wolf may also be showing low nucleotide diversity in part of this region, possibly from introgression with G. magnirostris?).

Nucleotide diversity in the ALX1 region

Nucleotide diversity in the ALX1 region

G. fortis populations show substantial diversity in beak shape, and so the authors then genotyped an additional 62 birds from this species and found a textbook association between beak shape and genotype (figure 3e below; BB is blunt haplotype homozygote, PP is pointed haplotype homozygote, and BP is heterozygote). While beak morphology certainly involves multiple genes, as evidenced by the 15 significant genomic regions, their work shows that ALX1 alone is one of the most important, if not the most important contributor.

Linear regression analysis of beak shape score by genotype

Linear regression analysis of beak shape score by genotype

Conclusions

The authors put in a tremendous effort to sequence the genomes of all of these individuals, representing each of the 15 Darwin’s finches, and once these are made accessible to the public they will no doubt be a valuable resource for any future studies involving those species, and indeed for anyone interested in the field of adaptive radiation. However, given such a large dataset, it would have been nice to see some additional work done, e.g. an assessment for possible differential gene expression of the genes within the 15 observed ZFST peaks, or further analyses of some of the other genes found in the ZFST peaks. I wonder also whether they might be able to apply an approach used in Zhan et al. (2014), which was used to identify regions of the genome associated withmigratory behavior in Monarch butterflies. This, or a similar approach, might yield more information than only scanning for high FST.

Update 21/10/2015: a previous version of this post stated incorrectly that the species tree from Farrington et al. (2014) was based largely on mitochondrial DNA.

Lamichhaney, Sangeet, Jonas Berglund, Markus Sällman Almén, Khurram Maqbool, Manfred Grabherr, Alvaro Martinez-Barrio, Marta Promerová, et al. “Evolution of Darwin’s Finches and Their Beaks Revealed by Genome Sequencing.” Nature 518 (2015): 371–375. http://www.nature.com/doifinder/10.1038/nature14181.

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Convergent evolution of the genomes of marine mammals

ResearchBlogging.org

Introduction

Convergent evolution is the independent evolution of similar features in species of different lineages. Marine mammals from different mammalian orders share several phenotypic traits adapted to the aquatic environment is a very classic example of convergent evolution. Although there are potentially several genomic routes to reach the same phenotypic outcome, it has been suggested that the genomic changes underlying convergent evolution may to some extent be reproducible and that convergent phenotypic traits may commonly arise from the same genetic changes. To investigate convergent evolution at the genomic level, the authors present high-coverage whole-genome sequences for four marine mammal species: the walrus (Odobenus rosmarus), the bottlenose dolphin (Tursiops truncatus), the killer whale (Orcinus orca) and the West Indian manatee (Trichechus manatus latirostris)(figure 1). Here are some interesting results of this paper.

Fig 1: Phylogeny of 20 eutherian mammalian genome sequences, rooted with a marsupial outgroup.

Fig 1: Phylogeny of 20 eutherian mammalian genome sequences, rooted with a marsupial outgroup.

Detecting positively selected protein-coding genes

In order to study the molecular mechanism of convergence evolution, firstly, they focused on detecting positive selected protein-coding genes in all three orders; Branch-site likelihood ratio test is a powerful polygenetic method to detect relatively ancient selection. This test is useful for identifying positive selection along prespecified lineages that affects only a few sites in the protein. Applying branch-site likelihood ratio method, they totally tested a series of four different branches. One on the combined marine mammal branches and one on each of the individual branches leading to manatee, walrus and the order containing dolphin and killer whale (see the branches colored red in Fig. 1). They identified 191 genes under positive selection across the combined marine mammal branches, 5 after conservatively correcting for multiple testing.

Identifying Convergent amino acid substitutions in positively selected genes

Secondly, they focused on identifying convergent amino acid substitutions encoded within positive selected genes found in the first part. They found such parallel nonsynonymous changes in coding genes mapping to the same amino acid site in more than one marine mammal lineage were widespread across the genome. In a word, they identified 44 parallel nonsynonymous amino acid substitutions occurred along all 3 marine mammal lineages. To specifically, they found 15 of the 44 identical nonsynonymous amino acid substitutionsin all 3 marine mammal lineages encoded within genes evolving under positive selection in at least one lineage; 8 of these genes were inferred to have evolved under positive selection in the test including all 3 marine mammal lineages (Fig. 2 and Table 1).

Table 1 Positively selected genes that encode parallel substitution in all three marine mammal lineages

Table 1 Positively selected genes that encode parallel substitution in all three marine mammal lineages

Figure 2 Genome scans for convergence. Marine mammal genomes showed a large number of parallel substitutions (blue) that occurred along the branches of at least two marine mammal lineages since they evolved from a terrestrial ancestor. Parallel substitutions that occurred in positively selected genes are shaded red.

Figure 2 Genome scans for convergence. Marine mammal genomes showed a large number of parallel substitutions (blue) that occurred along the branches of at least two marine mammal lineages since they evolved from a terrestrial ancestor. Parallel substitutions that occurred in positively selected genes are shaded red.

Is phenotype associated with genotype identified in this study? Indeed, they found several of the 15 genes under positive selection have known functional associations that suggest a role in the convergent phenotypic evolution of the marine mammal lineages. For example, S100A9 and MGP encode calcium-binding proteins that have a role in bone formation, SMPX has a role in hearing and inner ear formation16, C7orf62 has known links to hyperthyroidism17, MYH7B has a role in the formation of cardiac muscle18 and SERPINC1 regulates blood coagulation19. These genes could therefore be linked to convergent phenotypic traits such as changes in bone density (S100A9 and MGP), which is high in shallow-diving species such as the manatee and walrus to overcome neutral buoyancy but low in deep-diving cetacean species that collapse their lungs to overcome neutral buoyancy.

For me, the most interesting result they found is an unexpectedly high level of convergence along the combined branches of the terrestrial sister taxa (cow, dog and elephant) to the marine mammals, for which there is no obvious phenotypic convergence. This finding suggests that the options for both adaptive and neutral substitutions in many genes may be limited, possibly because substitutions at alternative sites have pleiotropic and deleterious effects.

Summary

This paper nicely showed that convergent amino acid substitutions were widespread throughout the genome and that a subset of these substitutions were in genes evolving under positive selection and putatively associated with a marine phenotype. However, the authors also found higher levels of convergent amino acid substitutions in a control set of terrestrial sister taxa to the marine mammals. These results suggest that, whereas convergent molecular evolution is relatively common, adaptive molecular convergence linked to phenotypic convergence is comparatively rare.

Foote, A., Liu, Y., Thomas, G., Vinař, T., Alföldi, J., Deng, J., Dugan, S., van Elk, C., Hunter, M., Joshi, V., Khan, Z., Kovar, C., Lee, S., Lindblad-Toh, K., Mancia, A., Nielsen, R., Qin, X., Qu, J., Raney, B., Vijay, N., Wolf, J., Hahn, M., Muzny, D., Worley, K., Gilbert, M., & Gibbs, R. (2015). Convergent evolution of the genomes of marine mammals Nature Genetics, 47 (3), 272-275 DOI: 10.1038/ng.3198

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Evolution of Darwin’s finches and their beaks revealed by genome sequencing

ResearchBlogging.org

Introduction

Darwin’s finches from Galapagos and Cocos Island are classic example of young adaptive radiation, entirely intact because none of the species having become extinct as a result of human activity. They have diversified in beak sizes and shapes, feeding habits and diets in adapting to different food resources. Although traditional taxonomy of Darwin’s is based on morphology and has been largely supported by observations of breeding birds finches, in this paper, authors showed the results of whole-genome re-sequencing of 120 individuals representing all of the Darwin’s finch species inhabiting Galapagos archipelago (Fig. 1a) and two close relatives, trying to analyse patterns of intra-and interspecific genome diversity and phylogenetic relationships among the species.

Figure 1a. Sample location of Darwin’s finches

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Summary and comments of the paper

The authors analyzed location and phylogeny of Darwin’s finches and found widespread evidence of interspecific gene flow that may have enhanced evolutionary diversification throughout phylogeny. They also reported discovery of a locus with the major effect on beak shape. They generated 10x sequence coverage per individual bird and using 2×100 base-pair (bp) paired-end reads and found evidence of introgression from three sources: ABBA-BABA tests, discrepancies between phylogenetic trees based on autosomal and sex linked loc, and mtDNA. Extensive sharing of genetic variation among populations was evident, particularly among ground and tree finches, with almost no fixed differences between species in each group. Their maximum-likelihood phylogenetic tree based on autosomal genome sequences is generally consistent with current taxonomy showing several interesting deviations (Fig. 1b).

Figure 1b. Phylogeny of Darwin’s finches

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Revised and dated phylogeny of Darwin’s finches shows that the adaptive radiation took place in the past million years, with a rapid accumulation of species recently. Genomic characterization of the entire radiation revealed a striking connection between past and present evolution. Evidence of introgressive hybridization is found throughout the radiation, showing that hybridization always gives rise to species of mixed ancestry, which is explained in detail (species and location) in this paper. The most obvious morphological difference among Darwin’s finches concerns beak shape. The authors performed a genome wide scan on the basis of populations that are closely related but show different beak morphology. In this study, they indicated a polygenic basis for beak diversity, discovering 15 regions with strong genetic differentiation between groups of finches with blunt or pointed beaks. Their analysis revealed that ALX homeobox 1 is an excellent candidate for variation in beak morphology, because it encodes a paired-type homeodomain protein (transcription factor), that plays a crucial role in development of structures derived from craniofacial mesenchyme, the first branchial arch and the limb bud, and have influence on migration of cranial neural crest cells, highly relevant to beak development. They observed single nucleotide polymorphisms (SNPs) in ALX1 gene of various finch species and concluded that blunt haplotype has a long evolutionary history because it’s origin predates the radiation of vegetarian, tree and ground finches. The haplotype might have evolved by accumulating both coding and regulatory changes affecting ALX1 function. Natural selection and introgression affecting this locus have contributed to the diversification of beak shapes among Darwin’s finches and hence to their expanded utilization of food resources on different Galapagos islands.

Lamichhaney, S., Berglund, J., Almén, M., Maqbool, K., Grabherr, M., Martinez-Barrio, A., Promerová, M., Rubin, C., Wang, C., Zamani, N., Grant, B., Grant, P., Webster, M., & Andersson, L. (2015). Evolution of Darwin’s finches and their beaks revealed by genome sequencing Nature, 518 (7539), 371-375 DOI: 10.1038/nature14181

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The genomic landscape underlying phenotypic integrity in the face of gene flow in crows

ResearchBlogging.org

In this paper authors returned to the question about the role of interspecific gene flow for the evolution and species diversification. Authors studied hybrid zone between two bird classes of the all-black carrion crows (Corvus corone) and the gray-coated hooded crows (C. cornix). Their morphological hybrid zone in Europe gives the possibility to study the effects of introgression on evolution during early species divergence. Authors identified genome-wide introgression and showed the divergence in the expression levels of genes, implicated in plumage coloration in both species, and genes, involved in visual perception, that could be important for maintaining phenotypic differences and responsible for heterogeneity in introgression landscapes.

Principal results

Firstly, authors assembled a high-quality reference genome of one hooded crow male which was aligned to chicken and zebra finch genomes and, then, annotated through mRNA sequencing. Consequently, a set of 20.794 protein coding genes containing open reading frames of more than 100 amino acids was found. RNA seq data was used to validate identified in silico genes. Then, authors resequenced 60 genomes of unrelated birds from four populations of carrion and of hooded crows and found 8.44 million single-nucleotide polymorphisms (SNPs) segregated across all investigated populations. Interestingly, carrion and hooded crows shared just 5.27 million SNPs among all found. Authors also discovered substantial genome-wide gene flow across the hybrid zone. They observed that the major axes of genetic variation corresponded to hypothesized direction of special expansion out of Spain. Moreover, German carrion crows grouped more closely to both Swedish and Polish hooded populations than Spanish carrion crows (Figure 1). By using multiple tests, such as ABBA-BABA test, admixture analysis and coalescence-based parameter estimate of isolation-with migration model, authors proved extensive gene flow between hooded crows and the German carrion crows populations.
Further, mRNA sequencing analysis was performed on 19 individuals and five tissues to check gene expression divergence between species across the hybrid zone. However, authors observed low proportion (0.03% – 0.41%) of differently expressed genes across tissues in carrion and hooded crows. Most of differently expressed genes were responsible for plumage coloration and all found overexpressed genes were implicated in the melanogenesis pigmentation pathway (Figure 3). Nineteen of these 20 genes involved in melanogenesis were found underexpressed in the gray hooded crows. All differently expressed genes were related to growing feather follicles from the bird’s torso. Authors confirmed that gene expression bias was related to a broad spectrum of down-regulated genes implicated in melanogenesis pathway rather than to defect in melanin deposition due to various melanocytes density (Figure 4).
Then, authors investigated the landscape of genomic divergence through a 50-kb window-based approach which uses clustering algorithm reconstructing local genomic phylogenies without any a priori input hypothesis. They showed that only 0.28% of genome was divergent between carrion and hooded crows. Also, one 1.95-Mb genomic region located on chromosome 18 and exhibiting strong genetic differentiation between two species was found. This region had 81 of all 82 fixed sites between carrion and hooded crows and possessed 40 annotated protein coding genes. Moreover, it was characterized by marked reduced nucleotide diversity and differentiation in all populations and increased linkage disequilibrium (LD). Authors do not deny the possibility of inversion in this region. On Figure 2 authors demonstrated one region with recent, positive selection in hooded crows. This region had a lot of fixed hooded crow-specific derived variants and reduced values of Fu and Li’s D statistic (P < 0.05). Moreover, the region contained members of the voltage-gated calcium channel subunit gene (CACNG) family encoding for the transmembrane regulators of AMPA receptors. These proteins modulate activity of the microphtalmia-associated transcription factor gene MITF, a principal regulator of the melanogenesis (Figure 3C). Authors found 11 melanogenesis genes which were regulated by MITF and underexpressed in gray hooded crow feather follicles. Thus, the authors connect gene expression, color phenotypic differences and the signature of local divergent selection and postulate that a number of genes cause color divergence in crows. Further gene expression analysis revealed that regulator of G protein signaling 9 (RGS9), normally highly expressed in eye, together with members of SLC24 gene family, responsible for pigmentation, showed decreased expression levels in hooded crows.
To conclude, this paper underlines the significance of inversion for evolutionary process and role of sexual selection for phenotypic and genotypic differentiation.

Personal comment

This paper presents a great and complete work which deepens our understanding of the role of interspecific gene flow for the evolution and species diversification. However, on figure 1 authors showed the map of the European distribution of the carrion and hooded crows that does not linked to principal components PC1 and PC2. On my opinion, it should be better perform an analysis that links PCA to geographical coordinates, as, for example, Procrustes analysis (form of statistical shape analysis used to analyze the distribution of a set of shapes).

Poelstra, J., Vijay, N., Bossu, C., Lantz, H., Ryll, B., Muller, I., Baglione, V., Unneberg, P., Wikelski, M., Grabherr, M., & Wolf, J. (2014). The genomic landscape underlying phenotypic integrity in the face of gene flow in crows Science, 344 (6190), 1410-1414 DOI: 10.1126/science.1253226

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The genomic substrate for adaptive radiation in African cichlid fish

In African lakes, cichlid fishes are famous for large, diverse and replicated adaptive radiations. Nearly 1,500 new species of cichlid fish evolved in a few million years when environmentally determined opportunity for sexual selection and ecological niche expansion was met by an evolutionary lineage with unusual potential to adapt, speciate and diversify. The phenotypic diversity encompasses variation in behaviour, body shape, coloration and ecological specialization. The frequent occurrence of convergent evolution of similar ecotypes suggests a primary role of natural selection in shaping cichlid phenotypic diversity.

To identify the ecological and molecular basis of divergent evolution in the cichlid system, David et al. [1] sequenced the genomes and transcriptomes of five lineages of African cichlids, Pundamilia nyererei (endemic of Lake Victoria); Neolamprologus brichardi (endemic of Lake Tanganyika); Metriaclima zebra (endemic of Lake Malawi); Oreochromis niloticus (from rivers across northern Africa); Astatotilapia burtoni (from rivers connected to Lake Tanganyika). These five lineages diverged primarily through geographical isolation, and three of them subsequently underwent adaptive radiations in the three largest lakes of Africa. Authors comprehensively investigate the features from these massive genomic data. Here is some interesting finding:

Accelerated gene evolution was assessed by non-synonymous/synonymous ratio. Compare with stickleback fish, O. niloticus has significant higher ranks. And three gene, a ligand (bmp4), a receptor (bmpr1b) and an antagonist (nog2) in the BMP pathway, all known to influence cichlid jaw morphology, show accelerated rates of protein evolution in haplo-chromine cichlids.

East African cichlids, including O. niloticus, possess an unexpectedly large number of gene duplicates. The author found 280 duplication events in the lineage leading to the common ancestor of the radiations. And that was 4.5- to 6-fold increase in gene duplications relative to other clades, normalizing by the branch length. But again, same as high dN/dS analysis, there is no significant enrichment for particular gene pathway.

For the transposable elements insertion in different lineage, the authors claimed that there were three waves of TE insertions. And the TE inserted near the 5’ UTR increased gene expression significantly. Surprisingly, none of the five cichlid genomes showed any deficit of sense-oriented LINE insertions, which correspond to a time of transposable element insertions in the common ancestor of the haplo-tilapiine cichlids. This suggests that ancestral East African cichlids went through an extended period of relaxed purifying selection.

For people who interested in small RNA, the authors also found surprising excess number of novel microRNA emerge in cichlid and with wet lab experiment confirmation, these novel miRNAs were believed to alter gene expression in multiple organs.

Last but not the least, they also did a lot of population genetic analysis in closely related species of the genera Pundamilia, Mbipia and Neochromis, all of which are endemic to Lake Victoria. Because Lake Victoria is where the most recent radiation happened. Several hundred endemic species emerged within the past 15,000–100,000 years. Their results from Fst comparing suggests that (1) variation in coding sequence is most likely to be involved in the divergence of physiological and/or terminally differentiated traits like color; (2) regulatory variation is more important in morphological changes involving genes that have pleiotropic effects in developmental networks.

Conclusion:

Sometimes with massive interesting point, it is hard to get the simple answer for the ultimate question, why some species diversify so dramatically, some species did not. Here is the case for cichlid, which they try to address the question of what is the genomic substrate for adaptive radiation. The author’s conclusion is neutral and adaptive processes both make important contributions to the genetic basis of cichlid radiations.

Reference:

  1. Brawand D, Wagner CE, Li YI, Malinsky M, Keller I, Fan S, Simakov O, Ng AY, Lim ZW, Bezault E, Turner-Maier, J. Johnson J, Alcazar R, Noh HJ, Russell P, Aken B, Alföldi J, Amemiya C, Azzouzi N, Baroiller J-F, Barloy-Hubler F, Berlin A, Bloomquist R, Carleton KL, Conte MA, D’Cotta H, Eshel O, Gaffney L, Galibert F, Gante HF, et al.: The genomic substrate for adaptive radiation in African cichlid fish. Nature 2014.
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The genomic substrate for adaptive radiation in African cichlid fish

ResearchBlogging.org

Evolutionary diversification among species attracts the attention of scientist during long time. Adaptive radiation underlies evolution and comprises the rapid adaptation of a single lineage to its changed environment which provides new resources and opens new environmental niches. Among all biological groups which have undergone evolutionary adaptive radiation the cichlids have been more studied by biologists. In this paper, authors investigated the molecular mechanisms and genomic substrates triggering rapid evolutionary diversification in African cichlid fish through comparative analysis of genomes of five different African cichlid lineages, together with an examination of the genetic changes responsible for divergence in six closely related species from Lake Victoria. They found some differences in all investigated East African lineages compared to ancestral, including increasing gene duplication, an excess of non-coding elements, accelerated evolution of coding sequence and divergence in the expression levels connected with transposons insertions. They also discovered novel microRNAs that alter gene expression in cichlids and genome-wide diversifying selection in coding and regulatory elements. Thus, authors have concluded that multiple molecular mechanisms together with relaxed purifying selection can promote evolutionary diversification in African cichlid fish.
Principle results and discussion
Authors selected and sequenced the genome of five lineages of African cichlids: four members of the East African lineage, including Neolamprologus brichardi/pulcher from Lake Tanganyika characterized by older radiation, Metriaclima zebra from Lake Malawi, Pundamilia nyererei from Lake Victoria and Astatotilapia burtoni from Lake Tanganyika, as well as an ancestral lineage with low diversity Nile tilapia (Oreochromis niloticus). All these lineages diverged through geographical isolation and, then, three of them underwent evolutionary adaptive radiations. Figure 1 illustrates that cichlid phenotypic diversity is caused by natural selection and includes ecological specialization, variation in behaviour, body shape and coloration.
Authors found the high rate of nonsynonymous nucleotide substitutions in genes involved in morphological and developmental process in the East African lineages compared to ancestral that can indicate accelerated evolution. However, relaxed constraint and positive selection can also be associated with accelerated evolution. They also demonstrated that developmental genes implicated in the Bone Morphogenetic Proteins (BMP) pathway, including ligand (bmp4), receptor (bmpr1b) and antagonist (nog2), showed increased rates of protein evolution in haplochromine cichlids. Among 22 genes known to be involved in morphogenesis, body pigmentation and vision authors identified three that are supposed to undergo accelerated evolution, driven by new light condition in novel environment, and could be important for diversification of cichlids. These genes include endothelin receptor type B1 (ednrb1), green-sensitive opsin (kfh-g) and Rhodopsin (rho).
By using three different methods (read-depth analysis, gene and species tree reconciliation analysis and array comparative genomic hybridization analysis) Brawand et al. showed that the East African cichlids have a large number of gene duplicates that is illustrated on Figure 2. However, authors did not precise which method they applied to make this figure. Moreover, all three methods have evident constraints in detection of gene duplicates. This fact and expected low level of overlap between results cast doubt on the rational application of these methods together for study. According obtained results, cichlid specific gene duplicates were not related to particular categories of genes. Additionally, authors postulated that differences in the levels of duplicate genes expression may support evolutionary divergence of species. Duplicate gene pairs were categorized according their expression pattern among different tissues. Many of duplicates had increased specific expression in the testis that correlates with strong sexual selection observed in African cichlids.
Next part of the paper is devoted to analysis whether transposable elements (TE) alter gene expression. In each of investigated cichlid genome authors detected three waves of transposons insertion. Analysis of the distribution of TE insertions revealed that genes with TE insertions close to the 5’UTRs showed increased expression in all tissues in contrast with genes without transposon insertions. On the other hand, TE insertion near the 3’UTRs was associated with increased gene expression in all tissues except brain and skeletal muscles. Moreover, authors observed different orientation bias of transposable elements inserted within or near non-duplicated genes and TE occurring in introns of all investigated cichlid species. Based on these data, they discussed the long period of relaxed purifying selection during which transposable elements insertion happened.
The same idea was supported by further analysis of potential regulatory sequences. In all East African cichlids, authors found highly conserved noncoding elements (hCNEs) and accelerated CNEs (aCNEs) distributed in introns, intergenic regions or UTRs of protein coding genes and showed high rate of nucleotide substitutions, insertions and/or deletions. Interestingly, aCNEs functioned as enhancers and altered the expression of their target genes in contrast to hCNEs. Furthermore, identified novel microRNAs were also able to change target gene expression that is illustrated on Figure 3.
Finally, authors investigated patterns of genome-wide genetic variation of six closely related species from the most recent evolutionary radiation in Lake Victoria. They found that recent rapid speciation was related to genomically prevalent divergence. Moreover, they observed the minimal fixation of alternative alleles from divergent loci between species. Further analysis revealed that in morphologically divergent species there were no exonic SNPs whereas in introns an increasing proportion of SNPs was correlated with increasing Fst that is depicted on Figure 4. Thus, coding and regulatory polymorphism underlies the adaptive radiation of African cichlids and takes old alleles from standing variation.
Conclusions
Present study contributes to further understanding adaptive radiation in African cichlids. Complex approach used by authors reveals multiple genomic and evolutionary mechanisms underlying diversity of East African cichlids population including increased gene duplication, accelerated evolution of coding and regulatory elements, regulation of gene expression by novel microRNAs and transposons insertion, retention of ancient polymorphism. However, sometimes we saw an excess of data, especially in supplementary information, which can confuse the reader. In any case, this paper provides the great resource to deepen our understanding of factors affecting adaptive radiation.

Brawand, D., Wagner, C., Li, Y., Malinsky, M., Keller, I., Fan, S., Simakov, O., Ng, A., Lim, Z., Bezault, E., Turner-Maier, J., Johnson, J., Alcazar, R., Noh, H., Russell, P., Aken, B., Alföldi, J., Amemiya, C., Azzouzi, N., Baroiller, J., Barloy-Hubler, F., Berlin, A., Bloomquist, R., Carleton, K., Conte, M., D’Cotta, H., Eshel, O., Gaffney, L., Galibert, F., Gante, H., Gnerre, S., Greuter, L., Guyon, R., Haddad, N., Haerty, W., Harris, R., Hofmann, H., Hourlier, T., Hulata, G., Jaffe, D., Lara, M., Lee, A., MacCallum, I., Mwaiko, S., Nikaido, M., Nishihara, H., Ozouf-Costaz, C., Penman, D., Przybylski, D., Rakotomanga, M., Renn, S., Ribeiro, F., Ron, M., Salzburger, W., Sanchez-Pulido, L., Santos, M., Searle, S., Sharpe, T., Swofford, R., Tan, F., Williams, L., Young, S., Yin, S., Okada, N., Kocher, T., Miska, E., Lander, E., Venkatesh, B., Fernald, R., Meyer, A., Ponting, C., Streelman, J., Lindblad-Toh, K., Seehausen, O., & Di Palma, F. (2014). The genomic substrate for adaptive radiation in African cichlid fish Nature, 513 (7518), 375-381 DOI: 10.1038/nature13726

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The genomic landscape underlying phenotypic integrity in the face of gene flow in crows

ResearchBlogging.org
The role of interspecific gene flow in species diversification has long been debated and is increasingly appreciated. However, the effect of gene introgression on phenotypic divergences and genome heterogeneity remain unclear in case of early speciation. To investigate these questions Poelstra and colleagues studied the hybrid zone between the all-black carrion crows (Corvus corone) and the gray-coated hooded crows (C. cornix). Indeed, the absence of neutral genetic diversity between these two species and successful back-crossing of hybrids strongly contrast with the plumage coloration polymorphism that remained stable in natural populations. Moreover, colour assortative mating has been observed suggesting a prezygotic isolation and ongoing speciation. To investigate the causes of this stable phenotypes the authors first analysed the effect of gene flow on genome heterogeneity and then tried to link the observed gene flow heterogeneity with gene expression and phenotypes.

Genetic differentiation between hooded and carrion crows

First, they assembled and annotated a high-quality reference genome of one hooded male crow and identified 20’794 protein-coding genes. This reference genome was then used to aligned 60 genomes of unrelated individuals from two populations of carrion and two populations of hooded crows (Fig. 1). They identified 8.44 million of SNPs among which 5.27 millions were shared between carrion and hooded crows. Although the major axes of genetic variation is consistent with the hypothesised expansion out of Spain after the last glaciation maxima the German carrion crows clustered closer with local German hooded crows than Spanish carrion crows (Fig. 1, on which the points represent the genetic distances between population according to the axes 1 & 2 of the principal component analysis and not the geographical location of sampled populations). Gene flow between hooded and carrion crows was also supported by complementary analyses.

Fig. 1. The crow system. Species distribution and genetic distances

Fig. 1. The crow system. Species distribution and genetic distances

 

Gene expression divergence

Further more by estimating gene expression through mRNA sequencing (19 individuals, 5 tissues) they found that only between 0.03% and 0.41% of the genes were differentially expressed between the two species. Interestingly they observed that lots of these genes were implicated in plumage coloration. Especially expression bias in the growing feather follicles from the torso where hooded crows are grey and carrion crows black was predominated by genes implicated in the melanogenesis pigmentation pathway and under-expressed in hooded crows (19 of the 20 identified genes). They confirmed that this expression bias was not due to different melanocyte density (Fig. 4) but rather to a broad scale down-regulation of genes implicated in melanogenesis.

Fig. 4. Characterisation of feather melanocytes. There is no striking differences in melanocytes density.

Fig. 4. Characterisation of feather melanocytes. There is no striking differences in melanocytes density.

 

Genomic divergence and gene expression between the two species

The authors investigated the landscape of genomic divergence with a 50-kb window-based approach (Fig. 2A) and a free clustering phylogenetic reconstruction for each window (Fig 2C). Out of the phylogenetic trees they inferred that only 0.28% of the genome strongly differ between the two species. Both methods revealed a 1.95 MB region exhibiting extreme genetic differentiation and regrouping 81 of all 82 fixed sites between the two species. Moreover, this region showed reduced nucleotide diversity and linkage disequilibrium with two local FST peaks connected by a saddle, revealing a possible inversion.

Fig. 2. Genomic landscape of divergence. (A) Pairewise genetic differentiation in 50-KB sliding windows across the genome. (B) The largest and most extrem genetic differentiation. (C) Localized phylogenetic patterns within the genome.

Fig. 2. Genomic landscape of divergence. (A) Pairewise genetic differentiation in 50-KB sliding windows across the genome. (B) The largest and most extrem genetic differentiation. (C) Localized phylogenetic patterns within the genome.

In the centre of one of these two FST peaks one region showed evidence for recent positive selection in hooded crows (enriched for fixed hooded crow specific variants and reduced values of Fu and Li’s D statistic (P < 0.05)). This region contains some CACNG genes that code for regulators influencing the transcription factor gene MITF. This transcription factor is a central regulatory element of the melanogenesis pathway (Fig. 3C) and regulates at least 11 melanogenesis genes under-expressed in the hooded crows. Therefore, the authors suggest a link between gene expression, colour phenotype and the signature of local divergent selection. Two others differentially expressed melanogenesis genes were located in divergent genomic regions. Yet, multigenic architecture of the colour trait is consistent with the colour polymorphism observed in the hybrids.

Fig. 3. The functionnal genomic basis of plumage colour differences. (A) Feather follicules used for gene expression. (B) Percentage of all expressed genes (white) and melanogenesis genes (striped) inferred to be differentially expressed. (C) Schematic overview of the melanogenesis pathway.

Fig. 3. The functionnal genomic basis of plumage colour differences. (A) Feather follicules used for gene expression. (B) Percentage of all expressed genes (white) and melanogenesis genes (striped) inferred to be differentially expressed. (C) Schematic overview of the melanogenesis pathway.

One gene stepped aside of the other one; the gene RGS9 which play a role in visual perception in vertebrates. This gene was underexpressed in hooded crows (including expression in eye). Besides its implication in visual perception alternative splicing forms (present in crows) of RGS9 play a role in dopamine regulation and opioid signalling in the brain and therefore may influence the observed assortative mating.

To conclude this paper showed that small local peaks of divergence (less than 1% of the genome, also called “speciation island”) is sufficient to maintain strong phenotypic differences between both species despite considerable gene flow. Moreover, they showed that assortative mating and sexual selection can exclusively cause phenotypic differentiation and speciation as there is apparently no ecological selection between the two species.

Personal observations

This paper nicely linked local genetic differences, regulatory pathway, gene expression and finally phenotypic differentiation between two closely related species. Clearly the authors had to produced an important and complete work and were somehow lucky to find a straightforward explanation. Yet, they provided evidences for several debated questions, as speciation without ecological selection, gene flow heterogeneity and “speciation island”, species identity even under important gene flow and the probable role of inversions in evolution.

Poelstra, J., Vijay, N., Bossu, C., Lantz, H., Ryll, B., Muller, I., Baglione, V., Unneberg, P., Wikelski, M., Grabherr, M., & Wolf, J. (2014). The genomic landscape underlying phenotypic integrity in the face of gene flow in crows Science, 344 (6190), 1410-1414 DOI: 10.1126/science.1253226

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Crossovers are associated with mutation and biased gene conversion at recombination hotspots

ResearchBlogging.org

Meiosis is an important biological process by which combination of various types of the genes called alleles, are segregated and packed in each germ cell waiting to be transferred and expressed in descendants. This combinations of alleles are products of chromosomal crossovers (COs) during meiotic recombination, which increases the genetic diversity of gametes. Recombination may cause local mutagenic effect at crossover sites with recurrent double strand breaks (DSBs) and thus be the source of sequence variation too.

SUMMARY OF THE PAPER

By sequencing a large number of single sperm DNA molecules, the authors showed that meiosis is an important source of germline mutations and consequently gene variation. They found more de novo mutations in molecules with COs then in molecules without a recombination event by amplifying single CO products, using allele-specific PCR, at two previously identified recombination hotspots (HSI and HSII) from a pool of sperm. The binding site used by the human recombination machinery contains PRDM9 (PR Domain Containing 9), very polymorphic in humans. In order to investigate why sequence diversity positively correlates with high recombination activity regions, the authors sequenced 5,796 COs in total, including both reciprocal recombination products from 6 Caucasian donors. As a control they screened single nonrecombinants (NRs) in the same region and subset of donors using the same experimental conditions.
To adjust CO mutation frequencies, authors used mutation frequency of NRs as a control, which are combination of rare de novo mutations and PCR artefacts. COs had a mutation frequency nearly 3.6 times higher than NR control (0.29% de novo mutations per CO of which 50% occurred between the DSB and the CO breakpoint, 348 nucleotides away from hotspot center (Fig. 1A), and it was similar for both hotspots (HSI and HSII), but most of the donors actually came from HSI, so the authors focused more on data analysis of this hotspot.

Figure 1. COs, mutations, and CCOs in HSI.

Fig.1

This also suggests that the observed mutations are associated with CO formation and they are independent of other site-specific factors such as base composition. Mutation rate at hotspots (μ HS) showed that more active hotspots exert a stronger mutagenic effect than weaker hotspots. All the observed de novo mutations changed strong (S) CG into weak (W) TA base pairs and they all occurred mainly at CpG sites. This strong mutational bias at CpGs are not exclusive to COs. CpG dinucleotides generally have high mutation rates, but what explains high mutation level at COs containing CpG sites is that single stranded DNA arised from double strand break (DSB), is more susceptible for chemical modification leading to G → T conversion on single-stranded DNA, and repair of those mismatched base pairs is only possible by the recognition from repair machinery bounded for double stranded, which is not the case for single stranded resected DNA 3’-ends created after DSB (Fig. 2A). If the formation of single-stranded DNA at methylated CpG sites is the main driver for de novo mutations, then DSBs resolved alternatively as noncrossovers (NCOs) might also have a higher frequency of the mutations.

Figure 2. Model of CO-driven evolution.

Fig.2

Considering hotspot CpG sites, the authors also observed very high methylation level (83-88%), both, in testis and in sperm, pointing on the cellular states before and after meiosis, respectively. The authors also suggested that non-Mendelian segregation of alleles at hotspots, arised during DSB repair could be either a result of an initiation bias, in which DSB-suppressing alleles are used to repair the broken homolog, or gene conversion favoring GC-alleles leading to GC-biased gene conversion (g-BGC).
Biased transmission is favorised for GC alleles representative for g-BGC, rather than for an initiation bias. In the authors data it is shown that all of the donors are homozygous at the DSB site which makes initiation bias unlikely. Sites with the strongest evidence for unequal transmission favor strong (GC) vs weak (AT) alleles (Fig 1B). Authors observed that transmission bias affects also single nucleotide polymorphisms (SNPs), which can be preferentially transferred, regardless of whether they are near or away from DSB (Fig.1C). Initiation bias do not favor strong over weak alleles in humans and yeast, whereas gBGC does. Another potential source of gBGC in the 6,085 mapped COs is the formation of COs with rare, discontinuous conversion tracks containing two CO breakpoints, and it is called complex COs (CCOs). Heteroduplex tracts are formed in polymorphic regions during DSB. If there acts gBGC, COs will tend to include strong alleles and exclude weak alleles (Fig. 2B). How fast crossing over drives the decimation of a hotspot via mutagenesis and gBGC depends on how sequence changes affect CO frequencies, which is still a mystery.

CONCLUSIONS
This study contributes to the understanding of the sequence evolution at recombination hotspots. Authors suggested that GC-biased gene conversion (gBGC) is the dominant force shaping the nucleotide composition at hotspots during crossing over, and potentially in other recombination products, which might explain the high GC content associated with recombination. It is possible that gBGC is an adaptation to reduce the mutational load of recombination, knowing that mutation favors weak over strong nucleotides. Still, small sample size gives a little power for detecting potential differences between COs and NCOs.

Arbeithuber, B., Betancourt, A., Ebner, T., & Tiemann-Boege, I. (2015). Crossovers are associated with mutation and biased gene conversion at recombination hotspots Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1416622112

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Evolution at two levels of gene expression in yeast

ResearchBlogging.org

Protein abundances mainly determined by the balance of transcriptional and translational regulation. Because of the limited technology for the translational research, however, gene expression evolution was based almost entirely on studies of transcriptional regulation. With the quickly development of ribosome profiling–isolating and sequencing short fragments of mRNA bound by actively translating ribosomes–now we can study translational regulation conveniently and efficiently.

Simultaneous detection of regulatory divergence at two levels

In this paper, firstly, in order to assess the relative contributions of regulatory elements evolution to the changes in mRNA abundance and translation rate, the authors applied ribosome profiling and RNAseq to two species of Saccharomyces yeast (S. cerevisiae and S. paradoxus )and their interspecific hybrid (figure 1).

Screen Shot 2015-04-06 at 17.24.47

Figure 1. Identifying cis-regulatory divergence at two levels. In the example, the S. paradoxus allele (blue) is transcribed at a higher level than that of S. cerevisiae (red), as represented by the larger number of wavy lines. However, the S. cerevisiae allele has higher translational efficiency, as represented by the larger number of ribosomes per transcript (pairs of gray circles). The S. paradoxus mRNA cis bias manifests as a negative log2(Sc/Sp) ratio in the mRNA fraction. If translational efficiency was unchanged between alleles, the more abundant allele, in this case S. paradoxus, would produce more footprints in the Ribo fraction. Therefore the translational cis ratio is obtained by dividing the Sc/Sp Ribo fraction ratio by the mRNA fraction ratio (which is equivalent to a subtraction in log2). The net log2(Sc/Sp) translational cis ratio is positive, indicating cis bias favoring S. cerevisiae translation.

Screen Shot 2015-04-06 at 17.25.01

Figure 2. The relationship between cis-regulatory divergence at the mRNA abundance and translational levels. Divergence was detected only at the mRNA level for a large fraction of genes (orange circles), though greater than one-tenth of orthologs were significantly diverged only in translation (blue circles). Among orthologs diverged at both levels, we observed a significant excess opposing (red triangles) as compared with reinforcing changes (green squares). The number of orthologs in each class is indicated in the barplot. (S. cer) S. cerevisiae; (S. par) S. paradoxus.

Within hybrids, both alleles share the same trans-acting cellular environment. Therefore, different mRNA abundance or translation efficiency is caused by cis-regulatory divergence. By applied these methods, the authors showed cis-regulatory divergence in both transcription and translation are abundant, almost 35% orthologs have significant divergence in translational efficiency, as compared with 61% with significant divergence in mRNA abundance. Because they identified cis-regulatory elements change at two regulatory levels simultaneously, an interesting question will be asked is whether changes at the two levels could be reinforcing (acting at the same direction) or opposing (acting in opposite directions). Compared with transcriptional divergence, surprisingly, they found the majority of translation rate divergence has an opposed effect (figure 2).In other words, it means that translational divergence acts to buffer changes in mRNA abundance, leading to maintenance of similar protein abundances between species. This phenomenon makes me quite impressive, because it shows that measuring mRNA abundance to study the expression evolution is not appropriate for some genes its protein abundance are also determined by translation rate. At the same time, the authors found that trans-acting regulatory divergence is also widespread at both regulatory levels and has an opposing pattern between the two levels.

Polygenic selection at two levels of gene regulation

Screen Shot 2015-04-07 at 15.21.57

Figure 3. Detecting selection from patterns of ASE in hybrids. The example above shows ASE levels (indicated by the wavy lines) for four genes belonging to a particular functional category. Black ‘‘X’’s indicate down-regulating cis-regulatory differences between the parental alleles. For a given group of functionally related genes evolving neutrally, no bias is expected with respect to the directionality of ASE in hybrids (No selection). However, biased directionality, as in the case in which all down regulating mutations occurred along the S. cerevisiae lineage (Selection), indicates a history of lineage-specific selection acting on cis-regulation.

Secondly, the authors applied a recently developed approach to detect expression adaptation evolution (independently at the level of transcription and translation, as well as among all orthologs with reinforcing direction between the two regulatory levels) across functionally related groups of genes. The basic theory of this approach is based on the null hypothesis that under neutral divergence of cis-regulation, no consistent bias is expected in the relative parental direction of ASE (allele specific expression) among genes within a functional category. So, consistent directional bias across a functional group indicates that multiple independent cis-regulatory changes have altered gene expression in a coordinated fashion, and is evidence of lineage specific selection (figure 3). Totally, the authors tested 591 gene sets for deviation from neutral expected frequencies by means of a x2 test, and used a permutation framework to control for the number of tests performed. Then, the authors took S. cerevisiae strain S288c is more resistant to heavy metals than S. paradoxus strain because higher levels of both mRNA and translation in S. cerevisiae among genes whose loss leads to heavy metal sensitivity as an example to show how nature selection affected phenotype by shaping genotype. Their finding of natural selection on both levels of regulation, in some cases targeting the same gene sets, highlights the importance of considering both levels simultaneously.

Identification of conserved C-terminal peptide extensions

Screen Shot 2015-04-07 at 15.30.30

Figure 4. Evidence of stop-codon readthrough leading to C-terminal peptide extension. The translation initiation codons are indicated by the right-facing arrow, the annotated ORF by the thick black lines, and the canonical stop codon by the black triangles. The candidate C-terminal peptide extension is indicated by the gray line terminated by in-frame stop codons in the 39 UTR (gray triangles above the line for S. cerevisiae, and below for S. paradoxus). Dark shades (red, S. cerevisiae; blue, S. paradoxus) indicate nucleotide-level coverage of mRNA fraction reads, and light shades indicate Ribo fraction reads.

Liken alternative splicing, infrequent stop-codon readthrough–involves the ribosome inserting an amino acid into the growing peptide at a stop-codon position and continuing in-frame translation–is another way to increase peptide diversity. Taking advantage of multispecies riboprofiling data, next, the authors focused on searching for direct evidence of translation in putative C-terminal extensions at the transcriptome wide level. Results showed that putative C-terminal extension was detected in one or both species in 109 and 81 cases, respectively. For example, translation initiation factor eIF1A (TIF11) has conserved C-terminal extension between both species shown in (Figure 4). Tif11 is an essential protein that is involved in start codon identification whose C terminus interacts with Fun12, a GTPase also involved in initiation of translation. Stop-codon readthrough could potentially play a role in the regulation of this interaction. At the some time, they also observed several species-specific readthrough events, suggesting this may be an unappreciated source of regulatory divergence.

Personal opinions

Because the transcription variation was buffered by translation evolution, it proves this variation has some kind of harmful effect. In other words, it means the mutations caused transcription divergence between the two species are deleterious. So, I am quite wondering why these deleterious mutations got fixed among the population. In my opinion, two hypotheses may explain it.

First of all, a mutation on a trans factor may affect the gene expression of many genes. If the net fitness effect is positive, the mutation is favored by the positive selection, even though some genes’ expression may become suboptimal. Compensatory mutations provide a strategy to further improve the fitness. Alternatively, this kind of compensatory regulation was evolved to mitigate the trade-off (caused by pleiotropy) between gene expression abundance and some other traits (such as expression noise, timing, location and so on). Taking the expression abundance and noise as an example, because the regulation mechanisms of the both traits are coupled, if nature selection shapes the promoter architecture for decreasing expression noise(beneficial), it will also change the transcription abundance(deleterious). So, in order to compensate the deleterious effect caused by transcription level variation, translation rate evolved on an opposing direction.

Artieri, C., & Fraser, H. (2013). Evolution at two levels of gene expression in yeast Genome Research, 24 (3), 411-421 DOI: 10.1101/gr.165522.113

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