different mutation rates in different human populations

well this seems important! via race/history/evolution notes, an abstract from the society for molecular biology and evolution 2014 conference (in puerto rico! – teh scientists are always good to themselves whenever they can be (~_^) ):

Evidence for different mutation rates across human populations
Ron Do, David Reich
Department of Genetics, Harvard Medical School, Boston, USA

Although mutation rates (per base pair) have clearly changed across primate evolution, many analyses continue to assume that all present-day human populations have the same mutation rates. Recently, William Amos analyzed 1000 Genomes Project and Complete Genomics sequences and found evidence of significantly higher divergence rates on African than on non-African lineages since separation (W. Amos, PLoS One 4, e63048). The detected pattern was strongest in genomic regions of high polymorphism rate, a pattern that the author hypothesized was due to ‘heterozygote instability’, whereby gene conversion events surrounding heterozygous sites increase the mutation rate. To further test this observation, we measured the relative accumulation of mutations in lineages drawn from two different populations, using 25 deep genome sequences generated according to the same experimental protocol using the Illumina technology. We carried out pairwise comparisons of five sub-Saharan African (Dinka, Mandenka, Mbuti, San, Yoruba) and eight Non-African populations (Australian, Dai, French, Han, Karitiana, Mixe, Papuan, Sardinian) on all divergent sites. We observed statistically significant differences in the relative accumulation of mutations for many pairs of African and Non-African populations. Among the strongest differences is significantly more lineage-specific mutations in Mbuti than in Han Chinese (R=1.044, standard error (SE) =0.0015). On average, we observed about 1% more mutations on African lineages compared to Non-African lineages. We also observed some significant differences across non-African populations, with the Han Chinese who have experienced extreme expansions in population size associated with agriculture having more mutations than the Karitiana, a hunter-gatherer population from Amazonia who did not experience such expansions (R=1.015, SE=0.0014). The results are consistent across both European and African segments of the human reference sequence, so are not an artifact of reference sequence bias. Taken together, these results support the view that per-base pair mutation rates may be dynamically and substantially changing across humans.


wrt to greater number of mutations in african lineages: polygamy (and, therefore, older fathers)? life in the tropics?

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runs of homozygosity again

**update below**

here’s an exciting new paper!: Genomic Patterns of Homozygosity in Worldwide Human Populations. i don’t have access to the paper itself, but there are lots o’ neat figures and tables in the supplemental data [opens pdf] that relate to runs of homozygosity (roh). roh are identical stretches of dna within an individual’s genome (i.e. identical on each of the dna strands, paternally and maternally inherited). (roh shouldn’t be confused with blocks of identity by descent [ibd], which i did once! ibd blocks are identical stretches of dna as compared between different individuals, iiuc.)

recall that possessing lots of long roh indicates that one’s parents are/were quite similiar genetically speaking. that can be as a result of a couple of different genetic scenarios like (as greying wanderer has brought up a lot recently) simply being from a small sized population (i.e. having a small effective population size) and/or from regular inbreeding (consanguineous/endogamous mating). so, a population having a lot of long roh is either small and/or inbreeds a lot. populations having LOTS of short roh have probably been through some sort of bottleneck (see previous post).

in the paper i looked at in that previous post, the researchers had looked at the different roh lengths for large, regional populations like “europeans” or “east asians.” amongst other things, they had found that some of my regular inbreeders — the fbd marriage folks — had some of the highest numbers of medium and long roh, a state of genetic affairs which likely reflects their long-term close mating patterns. interestingly, the researchers had found that east asians had roh lengths similar to those of europeans across the board, something which surprised me since, at least according to what i’ve been reading, east asians (i.e. the chinese) have been inbreeding for a much longer time than europeans. one drawback of that previous study, though, was that, apart from the french, most of the european populations they looked at were peripheral groups who have had a tendency to inbreed more than my “core” europeans (see mating patterns in europe series below ↓ in left-hand column).

the new paper suffers from some of the same problems since the data come from the same sources (hgdp-ceph and hapmap phase 3 populations), so northern europeans — apart from the french — aren’t included in this paper either. (what can you do? it’s early days yet. i look forward to when there’s lots more genetic data available out there for teh scientists to work with! (^_^) )

what the researchers in this paper have done, though, is to look at both the different mean lengths of roh in each of the different populations sampled AND they looked at total numbers of roh within individuals for each population. this has, i think, drawn out some interesting differences between the populations.

first, here are two graphics from the supplmental data (linked to above). click on each for LARGER views (they should open in new tabs/windows — you might have to click on them again there to super-size them).

i’ve highlighted a handful of populations i want to focus on ’cause i know a little something about their historic mating patterns: the bedouin (as a proxy for the arabs — note that the bedouin have probably inbred more than more settled arabs); italians (not sure if they’re northern or southern italians or a mix of both — however, there are tuscans in the samples with which these “italians” can be compared); pathan or pastuns (more fbd marriage folks, like the bedouins/arabs); and han chinese (there are some northern han chinese with whom this groups can be compared). ok. here are the charts:

as you can see, the researchers have split up the roh into three classes (note that the short and medium classes here are a lot shorter than those in the paper looked at previously):

– A: 0.25-0.40 Mb (short)
– B: 0.6-1.2 Mb (medium)
– C: 0-35 Mb (long)

the interesting thing in the first chart above (Fig. S3 – Mean ROH Length for Each of the Three Size Classes in Each Population), is that the han chinese have lower means of roh length in all of the size classes compared to the other populations i’ve highlighted. in the previous study, the researchers found that east asians had similar means to europeans for all roh lengths. i found this surprising since, from what i’ve read, the han chinese have been inbreeding for a longer period of time than europeans. what might be confounding the results though, once again, is the fact that nw europeans (the outbreeders extraordinaire) are not really included in either of these studies apart from a handful of french samples.

in this latest study, both the bedouin and the pashtun, for instance, have higher means — and wider spreads — of long (class C) roh than the italians, which is what i would’ve expected since those two groups (the bedouins and the pashtuns) are, being fbd marriage folks, serious inbreeders. perhaps the reason the han chinese long roh mean is comparatively low is partly due to the fact that they historically practiced mother’s brother’s daughter (mbd) marriage which doesn’t push towards such close inbreeding as fbd marriage. still, i would’ve expected to see greater means of roh for the chinese than the italians — or, at least, around the same. not so much lower. (unless the italians practiced fbd marriage, too — or fzd marriage — but i don’t think so.)

if you look at the second chart (Fig. S4 – Total Number of ROH in Individual Genomes), however, you’ll see that, overall, the han chinese have more short, medium and long roh totally in individual genomes than any of the other three populations i’ve highlighted. both the bedouins and the pashtuns have greater numbers/wider total spread of long roh than the italians, but the han chinese have a much greater total number of long roh than any of the other three groups — three or four times as many.

but they’re, on average, shorter long roh don’t forget. (confusing, eh?!)

perhaps this is what you get when you have — as the chinese have had — a pretty good-sized effective population size for such a long time. there have been a LOT of han chinese for — wow — millennia.

so, it looks like this (in this order of inbrededness — i think):

– bedouins: highest mean, and very wide spread, of long roh; high total numbers, and widest spread, of long roh.
– pashtun: low mean, but widest spread, of long roh; low total number, but very wide spread, of long roh.
– han chinese: very low mean, and very narrow spread, of long roh; highest total numbers, and wide spread, of long roh.
– italians: low mean, and rather wide spread, of long roh; very low total number, and very small spread, of long roh.

other interesting points are that:

– the tuscans/tsi (toscani) appear to have lower short, medium and long mean roh than the generic “italian” category. however, the tuscans have lower total numbers of long roh than the “italians” while the toscani (tsi), on the other hand, appear to have a greater total number of long roh than the “italians.” while the tuscan samples and the toscani/tsi samples are from different studies (hgdp vs. hapmap), they are all supposed to be from tuscany, so it’s surprising that they’re so different. perhaps the individuals in the toscani/tsi sample were more closely related somehow?

– the northern han samples have lower short, medium and long mean roh than the generic “han” category. this would fit my general impression that historically inbreeding has been greater in southern china than in the north. however, the total number of long roh are greater in the northern han sample than in the “han” sample. not sure what that means.

don’t forget that there can be all sorts of reasons for differences in roh: inbreeding vs. outbreeding, yes, but also effective population size, population movement (migration in or out), bottlenecks, etc. i just happen to be interested in trying to pick out the effects of inbreeding/outbreeding — if possible.

**update – here are a couple of excerpts from the article (thnx, b.b.!) [pgs. 277, 279-281]:

“Size Classification of ROH

“Separately in each population, we modeled the distribution of ROH lengths as a mixture of three Gaussian distributions that we interpreted as representing three ROH classes: (A) short ROH measuring tens of kb that probably reflect homozygosity for ancient haplotypes that contribute to local LD [linkage disequilibrium] patterns, (B) intermediate ROH measuring hundreds of kb to several Mb that probably result from background relatedness owing to limited population size, and (c) long ROH measuring multiple Mb that probably result from recent parental relatedness….

“In each population, the size distribution of ROH appears to contain multiple components (Figure 2A). Using a three-component Gaussian mixture model, we classified ROH in each population into three size classes (Figure 2B): short (class A), intermediate (class B), and long (class C). Size boundaries between different classes vary across populations (Table S1); however, considering all populations, all A-B boundaries are strictly smaller than all B-C boundaries (Figure 2C). The mean sizes of class A and B ROH are similar among populations from the same geographic region (Figure S3), with the exception that Africa and East Asia have greater variability. The class C mean is generally largest in the Middle East, Central/South Asia, and the Americas and smallest in East Asia (Figure S3), with the exception that the Tujia population has the largest values. In the admixed Mexican population (MXL), mean ROH sizes are similar to those in European populations. In the admixted African American population (ASW), however, mean ROH sizes are among the smallest in our data set, notably smaller than in most Africans and Europeans.

“Geographic Pattern of ROH

Several patterns emerge from a comparison of the per-individual total lengths of ROH across populations (Figure 3). First, the total lengths of class A (Figure 3A) and class B (Figure 3B) ROH generally increase with distance from Africa, rising in a stepwise fashion in successive continental groups. This trend is similar to the observed reduction in haplotype diversity with increasing distance from Africa. Second, total lengths of class C ROH (Figure 3C) do not show the stepwise increase. Instead, they are higher and more variable in most populations from the Middle East, Central/South Asia, Oceania, and the Americas than in most populations from Africa, Europe, and East Asia. This pattern suggests that a larger fraction of individuals from the Middle East, Central/South Asia, Oceanis, and the Americas tend to have higher levels of parental relatedness, in accordance with demographic estimates of high levels of consanguineous marriage particularly in populations from the Middle East and central/South Asia, and it is similar to that observed for inbreeding-coefficient and identity-by-descent estimates. Third, in the admixed ASW and MXL individuals, total lengths of ROH in each size class are similar to those observed in populations from Africa and Europe, respectively (Figure 3).

“The total numbers of ROH per individual (Figure S4) show similar patterns to those observed for total lengths (Figure 3). However, in East Asian populations, total numbers of class B and class C ROH per individual are notably more variable across populations than are ROH total lengths.”

previously: runs of homozygosity and inbreeding (and outbreeding) and ibd and historic mating patterns in europe

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cousin marriage rates in modern china

surveys of late-twentieth century cousin marriage rates in urban china — places like beijing and shanghai — have found very modern marriage patterns, i.e. very low consanguinity rates (0.7% – 0.8% of all marriages between 1949-67 in those two cities being between first- and second-cousins).

rural areas, otoh, have remained more inbred — rural hubei province having rates between 2.8% – 4.3% between 1949-67.

zhaoxiong found that just the first-cousin marriage rate in lijiawan village in hubei between 1949-93 (note that cousin marriage in china has been technically illegal since 1980) was 8.4%. that’s quite a bit higher than the rates above, especially considering that it doesn’t include second-cousin marriages (the rates above do — who knows how many second-cousin marriages there were in lijiawan?).

zhaoxiong also found that mother’s brother’s daughter (mbd) marriage was the most common form, followed by mother’s sister’s daughter (mzd) and, then, father’s sister’s daughter (fzd). nobody married their father’s brother’s daughter (fbd).

as wang, et. al., point out: “[T]here is a long history of consanguineous marriage in China….” however, cousin marriage rates in china have been dropping since at least the middle of the twentieth century — but they’re still pretty high in rural communities.

the genetic ties are starting to loosen in china. if they keep it up, that could prove to be a good thing in terms of having a more cohesive rather than a clannish society. don’t ask me how many generations they’ll need to make this happen! wish i could be around in a few hundred years to see how it worked out for them. (^_^)

many thanks to m.g. for the zhaoxiong article! (^_^)

previously: cousin marriage in china and abridged history of cousin marriage in china and china today… and china and landlordism and what else happened during the middle ages?

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abridged history of cousin marriage in china

maybe it’s not even that. it’s more of a basic (edit: and tentative!) outline of the history of cousin marriage in china:

3rd century b.c.

– cross cousin marriage practiced: so that’s either father’s sister’s daughter marriage or mother’s brother’s daughter marriage.
bilateral cross cousin marriage: that’s two clans or lineages swapping brides back-and-forth [pgs. 629-30]:

“Granet also discusses cross-cousin marriage in ancient China…. Granet cites evidence to show that two clans would stand in a reciprocal relationship such that the members of one clan would always marry members of the other…. There were many clans which presumably, if Granet is correct, were arranged in pairs by this system. The women of the two clans would be particularly eager for its continuance, as it would bring their own kin into their husband’s clan….

“The evidence from terminology for cross-cousin marriage in ancient China is very complete.”

624-907 a.d.

– cousin marriage possibly banned during the tang dynasty (the tang code dates to 624 a.d.) [pg. 43]:

“The clause in the T’ang Code is sometimes expanded to include prohibition against cross-cousin marriage…. The clause seems to indicate only parents’ cross-cousins [so first-cousins once removed – hbd chick], not one’s own cross-cousins; if so, the interdiction is against inter-generation marriage rather than cross-cousin marriage. But the T’ung tien seems to show that during the T’ang period marriage with cross-cousins and mother’s sister’s daughter was actually prohibited.”

1364-1644 a.d.

– cousin marriage is prohibited in the ming code [pgs. 43-44]:

“Legal prohibition, however, came rather late, the first definite clause being found in the Ming Code. Since enforcement of this law proved rather difficult, in the Ch’ing [Qing] Code this interdiction was invalidated by another clause, immediately following it, which allowed such marriages.

“Footnote 41: G. Jamieson: Translations from the General Code of laws of the Chinese Empire, Chapter 18: ‘A man cannot marry the children of his aunt on the father’s side, or of his uncle or aunt on the mother’s side, because though of the same generation, they are within the fifth degree of mourning.” But a little later in the Li, it reads: ‘…In the interest of the people it is permitted to marry with the children of a paternal aunt or of a maternal uncle or aunt.'”

1644-1912 a.d.

– qing dynasty reverses cousin marriage ban (see above).


– cousin marriage prohibited in the Marriage Law of the People’s Republic of China.

in the 3rd century b.c., according to the erya, the terms for cross-cousins (father’s sister’s daughter and mother’s brother’s daughter, i.e. the ones you could marry) were the same, and the terms for the other two types of cousins (father’s brother’s daughter and mother’s sister’s daughter) were distinct. at some point in time, i don’t know when, the terms shifted so that all the cousin types had the same name except the father’s brother’s daughter, i.e. the only one no one married [see feng]. a similar shift in cousin terminology occurred in germanic languages in the 1100-1200s. cousins used to be differentiated in germanic languages, but following (by a few hundred years) the ban on cousin marriage by the church, all cousins came to be referred to by just the one term.

so, at several points in chinese history, the emperors tried to put a stop to cousin marriage, but they never managed. the fact that there were laws against it means they thought, for whatever reasons, that it was a problem, so i’d guess that the practice was probably pretty common. common enough for the emperors to want to stop it anyway. you’re not supposed to marry your cousin in china nowadays — since 1980 — however, see this from an article published in 2001:

“Although the marriage rules that prevailed during the dynastic era of China’s history generally tolerated such marriages (Li 1950:99-100), they have been prohibited for genetic reasons in both mainland China and Taiwan since the 1980s (Tao, Wang, and Ge 1988:313; Liang 1995:14). In practice, however, this type of marriage continues in a great many villages (Wu, Yang, and Wang 1990:330).”

who knows what the frequencies of any of these cousin marriages were at any given time.

previously: cousin marriage in china

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cousin marriage in china

from “Rethinking cousin marriage in rural China”:

“This article considers cousin marriage rules among affines in rural Chinese culture, based on research in Hubei Province….

“Studies during the last several decades have proposed different explanations of cousin marriage among Chinese, but none provides an accurate and comprehensive principle to explain the rules that guide the selection of marriage partners among relatives in rural Chinese society….

“For the Chinese, qinqi (affines) are relationships created through marriage, and are sharply distinguished from members of one’s own lineage. In the kinship terminology, patrilateral parallel cousins are tang (FBS and FBD), but all patrilateral cross-cousins, matrilateral cross-cousins, and matrilateral parallel cousins are biao (remote) relatives for Ego, male or female.

“Marriage within the lineage, especially FBD marriage [father’s brother’s daughter marriage], is treated like marriage between kin and tantamount to sibling marriage. Because this type of marriage is strictly forbidden, both in custom and in law, it does not need attention here. (2) But marriages between other types of first cousins are regarded quite differently. FZD [father’s sister’s daughter marriage], MBD [mother’s brother’s daughter marriage], and MZD marriages [mother’s sister’s daughter marriage] for a male ego have usually been referred to as biao or zhong-biao (outside) marriages. Although the marriage rules that prevailed during the dynastic era of China’s history generally tolerated such marriages (Li 1950:99-100), they have been prohibited for genetic reasons in both mainland China and Taiwan since the 1980s (Tao, Wang, and Ge 1988:313; Liang 1995:14). In practice, however, this type of marriage continues in a great many villages (Wu, Yang, and Wang 1990:330).

Previous research indicates considerable regional variation in attitudes and preferences related to biao marriages. For example, in both Kaixiangong Village in Jiangsu Province, where Fei (1939) did fieldwork, and Phoenix Village in Guangdong Province, which Kulp (1925) studied, MBD marriage was preferred and FZD marriage frowned upon (Fei 1939:50-51; Kulp 1925:168). According to Hsu (1945:91), the people of West Town in Yunnan Province favored MBD marriage, tolerated MZD marriage, but disapproved of FZD marriage. On the basis of his fieldwork and that of Fei and Kulp, Hsu (1945:100) makes the generalization that MBD marriage is preferred all over China, whereas in most regions FZD marriage is not….

Controversy remains, however, as to whether among cousin marriages MBD marriage is preferred in every region of China. Freedman (1958:98-99), for example, contends that MBD marriage is not prevalent everywhere in China and certainly not in southeast China. Gallin (1963), based on his research in a Taiwanese village, considers that in China MZD marriage is not considered particularly problematic, and that MBD marriage is preferred over FZD marriage. Furthermore, MBD marriages are not favored so much as simply permitted, and FZD marriages tend to meet with disapproval more often than with tolerance. Gallin (1963:108) suggests that in some regions MBD marriages may be actively preferred, but in general they are merely considered acceptable.”

so historically — which is a loooong time in china — cousin marriage was very much a part of chinese marriage practices. but it sounds like the types and frequencies varied between regions — and prolly over time, too. china’s a big place, after all.

that’s why i questioned kirin, et. al.’s statement:

“This is not surprising because both of these groups [europeans and east asians] are mainly represented here by fairly large populations with no documented preference for consanguineous marriage.”

if they mean now — well, yessort-of. if they mean at all historically — and by that i mean anytime before the mid-twentieth century — then, no. that’s just not right.

i don’t have acess to the above article, but i’m gonna order it, so i’ll post more about chinese cousin marriage sometime soon(-ish). (^_^)

previously: china today… and what else happened during the middle ages? and china and landlordism and chinese kinship terms…

(note: comments do not require an email. snow day!)

more roh

in “Genomic Runs of Homozygosity Record Population History and Consanguinity” that i posted about yesterday, kirin, et. al., say:

“Europeans and East Asians have very similar ROH profiles in all but the shortest category (0.5-1 Mb). There are no significant differences between either the percentage of individuals with ROH of different lengths or sum length of ROH above different length thresholds (>1.5 Mb) for these two continental groupings (File S1). This is not surprising because both of these groups are mainly represented here by fairly large populations with no documented preference for consanguineous marriage.

ehhhhhhh … well … if they’re talking about now, i.e. in the present, then yeah — that’s probably pretty right. but many of the european populations that they looked at (i.e. from the human genome diversity project [hgdp]), regularly practiced some to quite a lot of consanguineous marriages up until fairly recently. (i haven’t checked into the asian populations that they looked at.)

the european populations that they looked at are: the adygeis, the basques, french folks, italians, orcadians, russians, sardinians and tuscans.

the adygeis are the circassians and it’s my understanding that they have avoided cousin marriage for quite some time, although they are endogamous (obviously). the russians — religious russians, anyway — avoid first- and second-cousin marriage. but the basques and the french have had some signficant amounts of consanguineous marriage up until quite recently. and the italians and sardinians?! holy toledo! of all of these groups, it’s probably the tuscans that have avoided cousin marriage for the longest. (dunno about the orkney islanders.)

like i said yesterday, if anything, kirin, et. al., have probably got some of the most inbred europeans in their sample.

anyway … i took at look at their supplemental info [opens pdf] and found that they’ve included data for the proportion (percentage) of the genomes from each group that are covered in “runs of homozygosity” (roh). the more roh in your — or your population’s — genome(s), the more inbred you (all) are (or maybe the smaller your gene pool is — see yesterday’s post). when i took out just the europeans plus the han chinese and japanese and a couple of other interesting groups, here’s what i got:

most of the european groups have the least number of roh (these are roh of all different lengths). the han chinese are like the italians or the sardinians, who have a long and recent history of close marriages (not so much the northern italians) — and the japanese even more so. wikipedia tells us that cousin marriage was preferred in china until the mid-twentieth century, so there you go.

and the father’s brother’s daughter’s marriage groups? their roh are higher than the inbred europeans, the han chinese and the japanese.

you can see here, too, that the japanese have greater numbers of longer roh than french people (the black circles are the japanese, the orange circles are the french) — that means more recent inbreeding amongst the japanese (click on image for LARGER view – should open in new tab/window):

interestingly, many balochis (green circles) have fewer and shorter roh than the french — many have more and longer. dunno what that tells us about the balochi. new blood? tribes merging with (fairly) unrelated tribes? just plain ol’ out-marriage?

here are the percentages of the genomes covered by roh for each of the populations in the study in ascending order. i tried to match the colors for the continental groupings from the chart in yesterday’s post — dunno if i succeeded?:

previously: runs of homozygosity and inbreeding (and outbreeding)

(note: comments do not require an email. balochi farmer. (^_^) )