S23-1

Cone ratio variation and heritability in free-ranging Rhesus macaques (Macaca mulatta)

Amanda D Melin^1,2,3, Rachel A Munds¹, Eve Cooper, Alex DeCasien^4,5, Mareike C Janiak^1,6, Linh Gia Lam¹, Sam Bauman⁷, Mike Montague⁸, Melween Martinez⁷, Shoji Kawamura⁹, James P Higham^4,5

¹1Department of Anthropology and Archaeology, University of Calgary, Canada
²2Department of Medical Genetics, University of Calgary, Canada
³3Alberta Children’s Hospital Research Institute, University of Calgary, Canada
⁴4Department of Anthropology, New York University, United States
⁵5New York Consortium in Evolutionary Primatology, New York, United States
⁶6School of Science, Engineering & Environment, University of Salford, United Kingdom
⁷7Caribbean Primate Research Center, University of Puerto Rico, Puerto Rico
⁸8Department of Neuroscience, University of Pennsylvania, Pennsylvania, USA
⁹9Department of Integrated Biosciences, University of Tokyo, Japan

Catarrhine primates (African and Asian monkeys and apes) differ from other mammals in that males and females both routinely possess trichromacy, i.e. color vision based on three retinal cone types maximally sensitive to long (L, reddish), medium (M, greenish), and short (S, blueish) wavelengths of light. The spectral tuning of the L, M and S opsins is conserved across the infraorder. However, the ratio of L to M cone expression within and between species is surprisingly variable and poorly understood. We took advantage of a rare sampling opportunity to study the retinal transcripts of 189 rhesus macaques (Macaca mulatta) from the large, pedigreed population living on Cayo Santiago, Puerto Rico. We quantified expression of L, M and S opsin genes using droplet digital PCR of cDNA transcribed from retinal (foveal) RNA. We conducted heritability analyses using animal models to estimate the additive genetic variance of the L:M cone ratio and S cone ratio. Rhesus macaques in our study possessed an essentially equal ratio of L and M retinal cones, with L:M ratio ranging from ca 1:2 to 2:1. The ratio of S cones relative to the other (L+M) cone population is ca. 1:7, with less interindividual variation. We detected a weak impact of sex on L:M ratio and evidence that S, but not L:M, cone ratios are heritable. Our results provide new data on the biology of color vision variation and evolution in a model species of high biomedical relevance, and contextualize the extraordinary variation observed in human L and M cones. Keywords: red-green color vision, opsin, trichromacy, retinal gene expression

S23-2

Network-based analysis of allele frequency distribution among multiple populations identifies adaptive genomic structural variants

Marie Saitou^1,2, Naoki Masuda², Omer Gokcumen²

¹Norwegian University of Life Sciences
²University at Buffalo

Structural variants have a considerable impact on human genomic diversity. However, their evolutionary history remains mostly unexplored. Here, we developed a new method to identify potentially adaptive structural variants based on a network-based analysis that incorporates genotype frequency data from 26 populations simultaneously. Using this method, we analyzed 57,629 structural variants and identified 577 structural variants that show high population differentiation. We further showed that 39 and 20 of these putatively adaptive structural variants overlap with coding sequences or are significantly associated with GWAS traits, respectively. Closer inspection of the haplotypic variation associated with these putatively adaptive and functional structural variants reveals deviations from neutral expectations due to (i) population differentiation of rapidly evolving multi-allelic variants, (ii) incomplete sweeps, and (iii) recent population-specific negative selection. Overall, our study provides new methodological insights, documents hundreds of putatively adaptive variants, and introduces evolutionary models that may better explain the complex evolution of structural variants.

S23-3

Molecular understanding of morphological variations in humans

Ryosuke Kimura¹

¹Graduate School of Medicine, University of the Ryukyus

Due to the breakthroughs in DNA typing/sequencing technology, the molecular basis of phenotypic variations in humans has been unraveled at an unprecedented pace. Especially, genome-wide association study (GWAS) is a powerful tool to detect genotype-phenotype associations. Genome-wide scans for selection (GWSS) can also be used to identify loci associated with population-specific phenotypes. Moreover, advances in 3D imaging technology enable us high-resolution analyses of morphological variations. Previous studies have identified a lot of genetic variants associated with morphological variations in humans. However, how the variants have effects on the morphology is still unclear in most cases. This symposium will be a great opportunity to discuss difficulties and perspectives for future studies.

S23-4

An approach to understand the phenotypic diversity of human populations using local medaka populations as a model

Takafumi Katsumura¹

¹Kitasato university school of medicine

Humans are spread over various environments on the earth and show local differences in various traits. Recent genome diversity analyses have revealed many genetic polymorphisms related to the local differences, but their functions and evolutionary significance are still insufficiently understood. Our group has studied genetic polymorphisms differentiated among local human populations using medaka (Oryzias latipes) as a model. We have shown that there are genetic polymorphisms in medaka populations found in human populations and that medaka in the Japanese archipelago has a single origin, similar to human population history, and have proposed the effective use of medaka local populations as an analogy for local human populations. In this presentation, I would like to present these results and future perspectives.

S23-5

Recent advances in understanding human genetic adaptation to cold environments

Kazuhiro Nakayama¹

¹Graduate School of Frontier Sciences, The University of Tokyo

Genetic adaptation to low temperature has been considered indispensable in human migration into high latitudes after out of Africa. The genome-wide scanning of natural selection in the subarctic human populations, for instance, indigenous Siberians and Greenland Inuits, identified possible candidate loci for cold adaptation in humans. However, these loci are still awaited to be studied deeply for their significance in human physiological responses to cold exposure. Recent advances in understanding human physiological responses to cold, especially the discovery of metabolically active brown adipose tissues in adults using nuclear medicine tests, have provided an opportunity to assess the previously reported loci for potential impact on cold adaptation. Moreover, loci that the previous population genetic studies could not identify have been discovered as hopeful candidate genes for the cold-adaptive responses.