Biology subjects

Kelley Harris

Publications and source records attributed to Kelley Harris.

3 recordsLinked to original sources

bioRxiv2015

The Genetic Cost of Neanderthal Introgression

Approximately 2-4% of genetic material in human populations outside Africa is derived from Neanderthals who interbred with anatomically modern humans. Recent studies have shown that this Neanderthal DNA is depleted around functional genomic regions; this has been suggested to be a consequence of harmful epistatic interactions between human and Neanderthal alleles. However, using published estimates of Neanderthal inbreeding and the distribution of mutational fitness effects, we infer that Neanderthals had at least 40% lower fitness than humans on average; this increased load predicts the reduction in Neanderthal introgression around genes without the need to invoke epistasis. We also predict a residual Neanderthal mutational load in non-Africans, leading to a fitness reduction of at least 0.5%. This effect of Neanderthal admixture has been left out of previous debate on mutation load differences between Africans and non-Africans. We also show that if many deleterious mutations are recessive, the Neanderthal admixture fraction could increase over time due to the protective effect of Neanderthal haplotypes against deleterious alleles that arose recently in the human population. This might partially explain why so many organisms retain gene flow from other species and appear to derive adaptive benefits from introgression.

Evolutionary Biology↗

bioRxiv2014

Recent evolution of the mutation rate and spectrum in Europeans

As humans dispersed out of Africa, they adapted to new environmental challenges including changes in exposure to mutagenic solar radiation. Humans in temperate latitudes have acquired light skin that is relatively transparent to ultraviolet light, and some evidence suggests that their DNA damage response pathways have also experienced local adaptation. This raises the possibility that different populations have experienced different selective pressures affecting genome integrity. Here, I present evidence that the rate of a particular mutation type has recently increased in the European population, rising in frequency by 50% during the 40,000-80,000 years since Europeans began diverging from Asians. A comparison of single nucleotide polymorphisms (SNPs) private to Africa, Asia, and Europe in the 1000 Genomes data reveals that private European variation is enriched for the transition 5-TCC-3[->]5-TTC-3. Although it is not clear whether UV played a causal role in the changing the European mutational spectrum, 5-TCC-3[->]5-TTC-3 is known to be the most common somatic mutation present in melanoma skin cancers, as well as the mutation most frequently induced in vitro by UV. Regardless of its causality, this change indicates that DNA replication fidelity has not remained stable even since the origin of modern humans and might have changed numerous times during our recent evolutionary history.

Genomics↗

bioRxiv2014

The projection of a test genome onto a reference population and applications to humans and archaic hominins

We introduce a method for comparing a test genome with numerous genomes from a reference population. Sites in the test genome are given a weight w that depends on the allele frequency x in the reference population. The projection of the test genome onto the reference population is the average weight for each x, [Formula]. The weight is assigned in such a way that if the test genome is a random sample from the reference population, [Formula]. Using analytic theory, numerical analysis, and simulations, we show how the projection depends on the time of population splitting, the history of admixture and changes in past population size. The projection is sensitive to small amounts of past admixture, the direction of admixture and admixture from a population not sampled (a ghost population). We compute the projection of several human and two archaic genomes onto three reference populations from the 1000 Genomes project, Europeans (CEU), Han Chinese (CHB) and Yoruba (YRI) and discuss the consistency of our analysis with previously published results for European and Yoruba demographic history. Including higher amounts of admixture between Europeans and Yoruba soon after their separation and low amounts of admixture more recently can resolve discrepancies between the projections and demographic inferences from some previous studies.

Genomics↗