Biology subjects

Feldman, M. W.

Publications and source records attributed to Feldman, M. W..

22 records · Page 2Linked to original sources

bioRxiv2017

An Unexpectedly Complex Architecture for Skin Pigmentation in Africans

Fewer than 15 genes have been directly associated with skin pigmentation variation in humans, leading to its characterization as a relatively simple trait. However, by assembling a global survey of quantitative skin pigmentation phenotypes, we demonstrate that pigmentation is more complex than previously assumed with genetic architecture varying by latitude. We investigate polygenicity in the Khoe and the San, populations indigenous to southern Africa, who have considerably lighter skin than equatorial Africans. We demonstrate that skin pigmentation is highly heritable, but that known pigmentation loci explain only a small fraction of the variance. Rather, baseline skin pigmentation is a complex, polygenic trait in the KhoeSan. Despite this, we identify canonical and non-canonical skin pigmentation loci, including near SLC24A5, TYRP1, SMARCA2/VLDLR, and SNX13 using a genome-wide association approach complemented by targeted resequencing. By considering diverse, under-studied African populations, we show how the architecture of skin pigmentation can vary across humans subject to different local evolutionary pressures.\n\nHighlightsO_LISkin pigmentation in Africans is far more polygenic than light skin pigmentation in Eurasians.\nC_LIO_LIKhoeSan[§] populations, which diverged early in human prehistory from other populations, have lightened skin pigmentation compared to equatorial Africans.\nC_LIO_LISkin color is highly heritable in the KhoeSan, but pigmentation variability is not well explained by previously discovered pigmentation genes.\nC_LIO_LIWe perform the first GWAS for pigmentation in African KhoeSan populations and identify canonical pigmentation loci near TYRP1 and in SLC24A5, as well as novel associations surrounding SMARCA2 and other genes.\nC_LI

genetics↗

bioRxiv2017

Random Drift With A Determined Outcome: A Parsimonious Null Model OfNeanderthal Replacement By Modern Humans Via Neutral Species Drift

The processes that led to the demise of the Neanderthals and their replacement by modern humans have been the object of speculation, research, and heated debate. Most hypotheses fall into one of two categories: one highlights the role of climate change, epidemics, or other environmental pressures in the Neanderthals demise, and the other attributes it to direct or indirect competition with modern humans, who seem to have occupied the same ecological niche. The latter are based on the assumption that modern humans benefited from some selective advantage over Neanderthals that led to the latters extinction. We show that a scenario that includes migration and selectively neutral species drift can explain the Neanderthals replacement and is in line with the archaeological evidence. Our model offers a parsimonious alternative to those that invoke external factors or selective advantage, and can represent a null hypothesis in assessing such alternatives. We show that for a wide range of parameters this hypothesis cannot be rejected. Moreover, we suggest that although selection and environmental factors may or may not have played a role in the interspecies dynamics of the Neanderthals and modern humans, the eventual outcome of these dynamics, the replacement of the Neanderthals, was the result of the hominid migration dynamics at the end of the middle Paleolithic, namely repeated migration of modern humans from Africa into the Levant and Europe.\n\nSignificance statementMultiple factors have been proposed as possible drivers of the extinction of the Neanderthals and their replacement by modern humans circa 40,000 years ago: climate change, epidemics, and - most prominently - a selective advantage, such as superior cognitive capacity of modern humans over Neanderthals. We propose an alternative model that includes only migration of modern humans out of Africa into the Levant and Europe. We show that, given that the two species occupied a similar ecological niche, modern humans were destined to replace the Neanderthals even under a neutral scenario in which neither species has a selective advantage.

evolutionary biology↗

bioRxiv2017

Segregation lift: A general mechanism for the maintenance of polygenic variation under seasonally fluctuating selection.

Most natural populations are affected by seasonal changes in temperature, rainfall, or resource availability. Seasonally fluctuating selection could potentially make a large contribution to maintaining genetic polymorphism in populations. However, previous theory suggests that the conditions for multi-locus polymorphism are restrictive. Here we explore a more general class of models with multi-locus seasonally fluctuating selection in diploids. In these models, loci first contribute additively to a seasonal score, with a dominance parameter determining the relative contributions of heterozygous and homozygous loci. The seasonal score is then mapped to fitness via a monotonically increasing function, thereby accounting for epistasis. Using mathematical analysis and individual-based simulations, we show that stable polymorphism at many loci is possible if currently favored alleles are sufficiently dominant with respect to the additive seasonal score (but not necessarily with respect to fitness itself). This general mechanism, which we call \"segregation lift\", operates for various genotype-to-fitness maps and includes the previously known mechanism of multiplicative selection with marginal overdominance as a special case. We show that segregation lift may arise naturally in situations with antagonistic pleiotropy and seasonal changes in the relative importance of traits for fitness. Segregation lift is not affected by problems of genetic load and is robust to differences in parameters across loci and seasons. Under segregation lift, loci can exhibit conspicuous seasonal allele-frequency fluctuations, but often fluctuations may also be small and hard to detect. Via segregation lift, seasonally fluctuating selection might contribute substantially to maintaining genetic variation in natural populations.

evolutionary biology↗

bioRxiv2016

Finite-sites multiple mutations interference gives rise to wavelet-like oscillations of multilocus linkage disequilibrium

Within-host adaptation of pathogens such as human immunodeficiency virus (HIV) often occurs at more than two loci. Multiple beneficial mutations may arise simultaneously on different genetic backgrounds and interfere, affecting each other's fixation trajectories. Here, we explore how these adaptive dynamics are mirrored in multilocus linkage disequilibrium (MLD), a measure of multi-way associations between alleles. In the parameter regime corresponding to HIV, we show that deterministic early infection models induce MLD to oscillate over time in a wavelet-like fashion. We find that the frequency of these oscillations is proportional to the rate of adaptation. This signature is robust to drift, but can be eroded by high variation in fitness effects of beneficial mutations. Our findings suggest that MLD oscillations could be used as a signature of interference among multiple equally advantageous mutations and may aid the interpretation of MLD in data.

genetics↗