Biology subjects

Haig, D.

Publications and source records attributed to Haig, D..

4 recordsLinked to original sources

bioRxiv2025

A human supergene: BRCA1, CCDC200, and U2 snRNAs

BRCA1 occurs on one of two major haplotypes in populations of European and Asian ancestry that show signs of selection and functional differences. Near-maximal linkage disequilibrium associated with these haplotypes extends for more than 300 kilobases from RND2 to RNU2. There is greater haplotypic diversity in populations from Africa, with the majority haplotype in Europe and Asia a minority haplotype in Africa. Recombination across this region is very rare or absent, both within Africa and outside of Africa, with haplotypes inherited as alleles of a supergene. The polymorphism appears to be maintained by some form of balancing selection. We analyzed the repeat structure of the RND2-RNU2 supergene using the CHM13 telomere-to-telomere genome assembly. The most notable feature is the highly regular array of 6.1-kb RNU2 repeats. Immediately adjacent to the RNU2 array are retroviral sequences that may play a role in the concerted evolution of the repeats. Other structure-forming sequences from the RND2- RNU2 region are predicted to be sources of replicative stress and may interfere with meiotic chromosome synapsis.

evolutionary biology↗

bioRxiv2025

An ultra-long heavy chain bovine antibody neutralizes SARS-CoV-2 and reacts broadly with sarbecoviruses.

The ongoing threat of new SARS-CoV-2 variants and other sarbecoviruses has driven efforts to develop broadly neutralizing monoclonal antibodies (mAbs). This study used immunized cattle, known for producing antibodies with ultra-long CDRH3 domains, to generate 33 mAbs, ten of which had ultra-long CDRH3s (>50 amino acids). Of these, mAbs P7 and 99, demonstrated broad and potent neutralization. Notably, mAb P7 neutralized all tested variants, including SARS-CoV-1, with IC50 values between 0.05 and 9.2 {micro}g/mL, and showed cross-reactivity with RBDs from various sarbecoviruses. Structural analysis revealed that mAb 99 binds the spike proteins RBD at the ACE2 binding site. Although the exact binding of P7 wasnt resolved, evidence suggests it targets a hidden epitope, promoting spike trimer dissociation via its extended CDRH3. In Syrian hamsters, both mAbs significantly reduced lung viral loads. These results support the potential of bovine-derived mAbs, particularly those with ultra-long CDRH3s, for future antiviral therapies.

immunology↗

bioRxiv2019

On the logic of Fisherian sexual selection

In Fishers model of sexual selection, a female preference for a male trait spreads together with the trait because their genetic bases become correlated. This can be interpreted as a greenbeard system: a preference gene, by inducing a female to mate with a trait-bearing male, favors itself because the male is disproportionately likely also to carry the preference gene. Here, we use this logic to argue that Fisherian sexual selection in diploids proceeds via two channels, corresponding to two reasons that trait-bearing males disproportionately carry preference genes: (i) trait-bearing males are disproportionately the product of matings between preference-bearing mothers and trait-bearing fathers, and thus trait and preference genes are correlated in trans; (ii) trait and preference genes come into gametic phase disequilibrium, and thus are correlated in cis. Gametic phase disequilibrium is generated by three distinct mechanisms: a recombination mechanism, a dominance mechanism, and a sexual admixture mechanism. The trans channel does not operate when sexual selection is restricted to the haploid phase, and therefore represents a fundamental difference between haploid and diploid models of sexual selection. We use simulation experiments to artificially eliminate the cis channel, and show that a preference gene can spread in its absence in the diploid model, but not in the haploid model. We further show that the cis and trans channels contribute equally to the spread of the preference when recombination between the preference and trait loci is free, but that the trans channel becomes substantially more important when linkage is tight.

evolutionary biology↗

bioRxiv2019

Microstructures amplify seemingly honest signals in carotenoid-colored tanagers

Red, orange, and yellow carotenoid-colored plumages have been considered honest signals of condition. We comprehensively quantified carotenoid signals in the social, sexually-dimorphic tanager genus Ramphocelus using scanning electron microscopy (SEM), finite-difference time-domain (FDTD) optical modeling, liquid chromatography-mass spectrometry (LC-MS), and spectrophotometry. Despite males having significantly more saturated color patches, males and females within a species have equivalent amounts and types of carotenoids. Male, but not female, feathers have elaborate microstructures which amplify color appearance. Expanded barbs enhance color saturation (for the same amount of pigment) by increasing the transmission of optical power through the feather. Dihedral barbules (vertically-angled, strap-shaped barbules) reduce total reflectance to generate "super black" plumage, an optical illusion to enhance nearby color. Dihedral barbules paired with red carotenoid pigment produce "velvet red" plumage. Together, our results suggest that a widely cited index of honesty--carotenoid pigments--cannot fully explain male appearance. We propose that males are selected to evolve amplifiers of honest signals--in this case, microstructures that enhance appearance --that are not necessarily themselves linked to quality.

evolutionary biology↗