AluInsertion Polymorphisms and Human Evolution: Evidence for a Larger Population Size in Africa

Abstract

Alu insertion polymorphisms (polymorphisms consisting of the presence/absence of an Alu element at a particular chromosomal location) offer several advantages over other nuclear DNA polymorphisms for human evolution studies. First, they are typed by rapid, simple, PCR-based assays; second, they are stable polymorphisms-newly inserted Alu elements rarely undergo deletion; third, the presence of an Alu element represents identity by descent-the probability that different Alu elements would independently insert into the exact same chromosomal location is negligible; and fourth, the ancestral state is known with certainty to be the absence of an Alu element. We report here a study of 8 loci in 1500 individuals from 34 worldwide populations. African populations exhibit the most between-population differentiation, and the population tree is rooted in Africa; moreover, the estimated effective time of separation of African versus non-African populations is 137,000 ± 15,000 years ago, in accordance with other genetic data. However, a principal coordinates analysis indicates that populations from Sahul (Australia and New Guinea) are nearly as close to the hypothetical ancestor as are African populations, suggesting that there was an early expansion of tropical populations of our species. An analysis of heterozygosity versus genetic distance suggests that African populations have had a larger effective population size than non-African populations. Overall, these results support the African origin of modern humans in that an earlier expansion of the ancestors of African populations is indicated.The Alu family of short interspersed elements is one of the most successful mobile genetic elements, having arisen to a copy number in excess of 500,000 within primate genomes in the last 65 million years (for recent reviews, see Okada 1991;Schmid and Maraia 1992; Batzer 1993, 1995). Alu repeats are thought to be ancestrally derived from the 7SL RNA gene and mobilize through an RNA polymerase III-derived transcript in a process termed retroposition. Each Alu sequence is ∼300bp in length; therefore, Alu repeats comprise ∼5% of the human genome.Alu sequences can be divided into different subfamilies or clades of related elements based on commonly shared diagnostic mutations. Here, we use the new standardized nomenclature to refer to various Alu subfamilies (Batzer et al. 1996a). Two of the most recently formed subfamilies of Alu elements within the human genome have been termed Ya5 and Ya8 (Batzer et al. 1990;. Members of the Ya8 Alu subfamily are characterized by all five of the Ya5 diagnostic mutations, as well as three additional diagnostic mutations. Be- GENOME RESEARCH 1061Cold Spring Harbor Laboratory Press on May 12, 2018 -Published by genome.cshlp.org Downloaded from cause both the Ya5 and Ya8 Alu subfamilies share a number of diagnostic mutations we refer to this lineage collectively as Ya5/8 (Batzer et al. 1996b). The Ya5/8 Alu subfamily lineage is comprised of 500-2000 elements that are restricted to the human genome (Arco...

The geographic distribution of the ACE II genotype: a novel finding

“…Saab et al (2004) have typed the ACE I/D gene polymorphism in the Lebanese population, where the homozygous II genotype accounted for 8 % of the sample -an incidence that was found to be atypically low relative to European and East Asian populations. These preliminary results suggested that the ACE II genotype frequency might vary according to a geographic trend, as has been postulated for other Alu insertion polymorphisms (Stoneking et al, 1997). The objective of the present study was to determine whether the ACE I/D gene polymorphism frequency did indeed correlate with geographic distance and then identify whether the ACE gene can be considered as a genetic marker for the past demography of human populations.…”

“…Broader conclusions, such as identifying the origin of a particular polymorphism on the basis of its relative frequency, are less controversial; and this is more so with Alu elements, which are considered to be highly stable polymorphisms, where deletion of newly inserted elements is a rare event (Stoneking et al, 1997). Low frequencies of the insertion are therefore indicative of the ancestral state, and African populations tend to have not only the lowest frequency of the insertion (Bayoumi et al, 2006) but also the greatest variation in frequency (Stoneking et al, 1997). On this basis it would appear that the ALU deletion within the ACE gene was, of the populations studied here, Middle Eastern in origin.…”

The ins and outs of population relationships in west-Mediterranean islands: data from autosomal Alu polymorphisms and Alu/STR compound systems

“…Eight human-specific Alu insertion polymorphisms (DM, HS2.43, B65, PV92, D1, F13B, A25 and TPA25) were typed using the primers and polymerase chain reaction (PCR) amplification conditions previously described in Stoneking et al (1997) and Edward and Gibbs (1992), with minor modifications. As for STRs, CD4 consists of a pentanucleotide (TTTTC) n repeat amplified according to Tishkoff et al (1996), with minor modifications.…”

“…These samples (see Fig. 1 for geographical location) come from the works of Stoneking et al (1997), Comas et al (2000) and Garcia-Obregon et al (2006, 2007. The consulted population data from CD4, F13B and DM STRs was obtained from the ALFRED database (Rajeevan et al 2005).…”

Molecular variability in Amerindians: widespread but uneven information

“…Low variability in three parameters was obtained in these two groups, compared to the others; and (c) Deka et al (1999) References: 1. Batzer et al (1994); Stoneking et al (1997); Novick et al (1998); 2. Gaedigk et al (1998) Deka et al (1991Deka et al ( , 1994Deka et al ( , 1999, Deka and Chakraborty (1999); Destro-Bistrol et al (2000); 10.…”