The evolutionary history and genomics of European blackcap migration

Seasonal migration is a taxonomically widespread behaviour that integrates across many traits. The European blackcap exhibits enormous variation in migration and is renowned for research on its evolution and genetic basis. We assembled a reference genome for blackcaps and obtained whole genome resequencing data from individuals across its breeding range. Analyses of population structure and demography suggested divergence began ~30,000 ya, with evidence for one admixture event between migrant and resident continent birds ~5000 ya. The propensity to migrate, orientation and distance of migration all map to a small number of genomic regions that do not overlap with results from other species, suggesting that there are multiple ways to generate variation in migration. Strongly associated single nucleotide polymorphisms (SNPs) were located in regulatory regions of candidate genes that may serve as major regulators of the migratory syndrome. Evidence for selection on shared variation was documented, providing a mechanism by which rapid changes may evolve

No Association between Personality and Candidate Gene Polymorphisms in a Wild Bird Population

Consistency of between-individual differences in behaviour or personality is a phenomenon in populations that can have ecological consequences and evolutionary potential. One way that behaviour can evolve is to have a genetic basis. Identifying the molecular genetic basis of personality could therefore provide insight into how and why such variation is maintained, particularly in natural populations. Previously identified candidate genes for personality in birds include the dopamine receptor D4 (DRD4), and serotonin transporter (SERT). Studies of wild bird populations have shown that exploratory and bold behaviours are associated with polymorphisms in both DRD4 and SERT. Here we tested for polymorphisms in DRD4 and SERT in the Seychelles warbler (Acrocephalus sechellensis) population on Cousin Island, Seychelles, and then investigated correlations between personality and polymorphisms in these genes. We found no genetic variation in DRD4, but identified four polymorphisms in SERT that clustered into five haplotypes. There was no correlation between bold or exploratory behaviours and SERT polymorphisms/haplotypes. The null result was not due to lack of power, and indicates that there was no association between these behaviours and variation in the candidate genes tested in this population. These null findings provide important data to facilitate representative future meta-analyses on candidate personality genes

The coefficients and associated 95% confidence intervals (CI) of the overdominant haplotype models for exploratory behaviour.

<p>The models are relative to individuals with no copies of the haplotype, subordinate is relative to dominant, male is relative to female.</p

Sequence, melting temperature (T_m) and length of product expected from each designed primer in base pairs.

<p>Sequence, melting temperature (T_m) and length of product expected from each designed primer in base pairs.</p

Schematic representation of the <i>DRD4</i> and <i>SERT</i> regions.

<p>Grey boxes represent exons and the dotted line introns. The vertical black lines indicate the locations of the primers used in this study.</p

The coefficients and associated 95% confidence intervals of the overdominant haplotype models for bold behaviour.

<p>The models are relative to individuals with no copies of the haplotype, subordinate is relative to dominant, male is relative to female.</p

The coefficients and associated 95% confidence intervals of the additive haplotype models for exploratory behaviour.

<p>The models are relative to individuals with no copies of the haplotype, subordinate is relative to dominant, male is relative to female.</p

Studies of wild bird populations have shown that exploratory behaviour is associated with polymorphisms in DRD4. Additionally high levels of anxiety, a characteristic of bold behaviour, and exploratory behaviour have been associated with polymorphisms in SERT.

<p>Studies of wild bird populations have shown that exploratory behaviour is associated with polymorphisms in DRD4. Additionally high levels of anxiety, a characteristic of bold behaviour, and exploratory behaviour have been associated with polymorphisms in SERT. Here we tested for polymorphisms in DRD4 and SERT in the Seychelles warbler (Acrocephalus sechellensis) population on Cousin Island, Seychelles, and then investigated correlations between personality and polymorphisms in these genes.</p

The coefficients and associated 95% confidence intervals of the additive haplotype models for bold behaviour.

<p>The models are relative to individuals with no copies of the haplotype, subordinate is relative to dominant, male is relative to female.</p

Methylglyoxal Scavengers Resensitize KRAS-Mutated Colorectal Tumors to Cetuximab

The use of cetuximab anti-epidermal growth factor receptor (anti-EGFR) antibodies has opened the era of targeted and personalized therapy in colorectal cancer (CRC). Poor response rates have been unequivocally shown in mutant KRAS and are even observed in a majority of wild-type KRAS tumors. Therefore, patient selection based on mutational profiling remains problematic. We previously identified methylglyoxal (MGO), a by-product of glycolysis, as a metabolite promoting tumor growth and metastasis. Mutant KRAS cells under MGO stress show AKT-dependent survival when compared with wild-type KRAS isogenic CRC cells. MGO induces AKT activation through phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin 2 (mTORC2) and Hsp27 regulation. Importantly, the sole induction of MGO stress in sensitive wild-type KRAS cells renders them resistant to cetuximab. MGO scavengers inhibit AKT and resensitize KRAS-mutated CRC cells to cetuximab in vivo. This study establishes a link between MGO and AKT activation and pinpoints this oncometabolite as a potential target to tackle EGFR-targeted therapy resistance in CRC.Role of methylglyoxal stress in the resistance of KRAS mutated human colon cancer to targeted therap