Do we really need theory? Population genomics: Do we really need theory? Fred Allendorf or Can’t we answer all of our questions by just generating more data?

For many decades, empirical population genetics lagged far behind theory developed by Sewall Wright, R.A. Fisher, J.B.S. Haldane, etc.

1920-1970: The early years Empirical data Analysis & interpretation Theory & models Analysis & interpretation

1971-2000: The golden years Empirical data Analysis & interpretation Theory & models Analysis & interpretation

2000-present: The “omic” years Theory & models Analysis & interpretation Empirical data

Chinook salmon in the Columbia River Since not one example of gene frequency has been published for the population in question, a hypothetical (although realistic) model will have to suffice. Ray Simon 1972 2015 Genotyped 1,956 individuals at 19,703 loci from 56 sample sites

Four million genotyped fish and counting: What we’ve learned about genetic stock identification in salmonids. Lisa Seeb

First and foremost, we needed population geneticists First and foremost, we needed population geneticists. These are geneticists who study DNA sequence variation in a species or a population and, from this, infer what happened to these species or population in the past. They can tell when populations split, whether they exchanged genes, and whether selection acted upon them.

1970 New printing available for $55 at Amazon.com

Available online for free We have the same situation in population genomics. People have vast amounts of data and do completely half-ass things with it because they don’t know any better. And, I wish there was some way of persuading people that we need to train students in the development and properties of the methods.  And that means population genetics. Available online for free

Felsenstein’s timeline of population genetics

2015 I am constantly appalled to see people go through the motions of performing HW and LD tests, reporting the results, and then completely ignoring them, even when significant deviations are found.  Few people know how to properly interpret multiple testing results, and most seem to have lost track of why it is essential to do these tests before using the data for other analyses.

FIS for 14,000 SNPs in two elk population samples (Luikart et al.)

2016 Inbreeding: Confusion between FIS and pedigree F FIS is not an estimate of the mean pedigree F of individuals. A high mean F is expected in small random mating populations because all individuals will be closely related, but the expected FIS is 0. In fact, FIS is expected to be <0 in very small populations because of allele frequency differences between males and females.

“Filtering loci out of HW proportions will remove all loci under selection.” Anonymous genomicist Papers use LDNE to estimate Ne in population samples known to have LD from sources other than drift (e.g., hybridization).

blue - traditional red – “genomics”

2016 Pedigree F Genomic measures

𝑰𝑩𝑫 𝒕𝒓𝒂𝒄𝒕 𝒍𝒆𝒏𝒈𝒕𝒉𝒔 𝒈𝒆𝒏𝒐𝒎𝒆 𝒔𝒊𝒛𝒆 = F Runs of Homozygosity Identical by descent (IBD) chromosome tracts 𝑰𝑩𝑫 𝒕𝒓𝒂𝒄𝒕 𝒍𝒆𝒏𝒈𝒕𝒉𝒔 𝒈𝒆𝒏𝒐𝒎𝒆 𝒔𝒊𝒛𝒆 = F

Single pair of chromosomes from Swedish collared flycatcher Ellegren et al., 2012, Nature Kawakami et al., 2014, Mol Ecol Single pair of chromosomes from Swedish collared flycatcher H = Proportion of heterozygous SNPs in 10Kb windows ~20 Mb, IBD tract Proportion of the genome IBD can be measured with incredible accuracy & precision using whole genome sequences with a good assembly!

R.A. Fisher We thus pass from a point-theory to a strand-theory. 1965

Pedigree F = 0.25 The proportion of the genome IBD varies greatly even between full sibs! They have all the same “Coefficient of Inbreeding”, but differ in the extent of homozygosity. R.A. Fisher (1965, p. 97)

Expected proportion of the genome IBD in progeny from the last two wolves.

RoH also provide information about the time since the inbreeding event (Fisher 1965). 2 gens 5 gens Length distribution of IBD segments from common ancestor 2, 5, and 10 generations back 10 gens

The Wrangel Island mammoth has 20% less heterozygosity than the Oimyakon mammoth.

RoH 23.3% 0.83% Wrangel Island mammoth Oimyakon mammoth:

IBD Comparison of individuals allows estimation of Ne over time.

Polyploid salmonid fishes (Allendorf et al. 2015)

2015 0 co 1 co ~50% ~50% (10 loci) (3,496 loci) 1983 Centromere Centromere

Thank you!